On this page you will find:
For even more information, check out our dynamic COVID Knowledge Bank created by our medical students keeping you up to date on news and journal articles related to the pandemic.
NOTE: Because we are focused one creating other content, this page is not updated as often as other pages. If interested in contributing to literature review, contact Elena Diller at ediller@augusta.edu
- Weekly updates regarding the latest COVID-19 literature
- Our reviews follow a PICO format: population, intervention, control and outcome. We include strengths, limitations and conclusions of the article as well.
For even more information, check out our dynamic COVID Knowledge Bank created by our medical students keeping you up to date on news and journal articles related to the pandemic.
NOTE: Because we are focused one creating other content, this page is not updated as often as other pages. If interested in contributing to literature review, contact Elena Diller at ediller@augusta.edu
Literature Reviews:
July 6- 13, 2020
Mental Health During Covid-19 Outbreak in China: a Meta-Analysis
Journal: Psychiatric quarterly
Journal: Psychiatric quarterly
Link: https://link.springer.com/article/10.1007%2Fs11126-020-09796-5
P: 27,475 Chinese adults >18 years, includes 12 studies that each were cross-sectional in design and utilized standard assessments for mental health
I: No intervention
C: No control
O: The pooled prevalence for anxiety and depression was 25% and 28%, respectively. Significant heterogeneity within both the group overall and subgroups suggest that further research be conducted in order to better understand the relationship between mental health and Covid-19.
Strengths: Meta-analysis with no evidence of publication bias via Begg’s or Egger’s test increasing generalizability.
Weaknesses: Some of the studies utilized relied on self-reported data leading to more inconsistency and may not have been as available to individuals with minimal internet or technology needed to participate.
Conclusion: The prevalence of anxiety and depression seen in this study and from healthcare workers from the previous SARS outbreak indicate that mental health is a priority that should be addressed as the pandemic continues.
P: 27,475 Chinese adults >18 years, includes 12 studies that each were cross-sectional in design and utilized standard assessments for mental health
I: No intervention
C: No control
O: The pooled prevalence for anxiety and depression was 25% and 28%, respectively. Significant heterogeneity within both the group overall and subgroups suggest that further research be conducted in order to better understand the relationship between mental health and Covid-19.
Strengths: Meta-analysis with no evidence of publication bias via Begg’s or Egger’s test increasing generalizability.
Weaknesses: Some of the studies utilized relied on self-reported data leading to more inconsistency and may not have been as available to individuals with minimal internet or technology needed to participate.
Conclusion: The prevalence of anxiety and depression seen in this study and from healthcare workers from the previous SARS outbreak indicate that mental health is a priority that should be addressed as the pandemic continues.
Efficacy and safety of interferon B-1a in treatment of severe COVID-19: A randomized clinical trial
Journal: ANTIMICROBIAL AGENTS and CHEMOTHERAPY
Journal: ANTIMICROBIAL AGENTS and CHEMOTHERAPY
Link: https://aac.asm.org/content/early/2020/07/08/AAC.01061-20
P: 81 adults (>18 years old) diagnosed with COVID-19 admitted during February 29th-April 3rd in a Tehran hospital. 42 in interferon group and 39 in control group.
I: Interferon B-1a in addition to national protocol medications (hydroxychloroquine plus lopinavir/ritonavir or atazanavir/ritonavir). 44 micrograms/mL of interferon B-1a was injected 3 times weekly for 2 consecutive weeks.
C: Received only national protocol medications (hydroxychloroquine plus lopinavir/ritonavir or atazanavir/ritonavir).
O: Time to clinical response was not significantly different between the groups. On day 14, 66.7% of interferon group were discharged while only 43.6% of the control group were discharged. 28-day overall mortality was significantly lower in the interferon group compared to the control group. Early administration significantly reduced mortality.
Strengths: First study regarding use of interferon B-1a in the treatment of COVID-19 and utilized a randomized control trial protocol.
Weaknesses: This study included patients from general, intermediate, and intensive care units during recruitment. The differences in the severity of the patients could influence the results.
Conclusion: Interferon B-1a significantly increased discharge rate on day 14 and decreased 28-day mortality. There was no change in time to clinical response. Survival rate was increased with early administration of interferon B-1a.
P: 81 adults (>18 years old) diagnosed with COVID-19 admitted during February 29th-April 3rd in a Tehran hospital. 42 in interferon group and 39 in control group.
I: Interferon B-1a in addition to national protocol medications (hydroxychloroquine plus lopinavir/ritonavir or atazanavir/ritonavir). 44 micrograms/mL of interferon B-1a was injected 3 times weekly for 2 consecutive weeks.
C: Received only national protocol medications (hydroxychloroquine plus lopinavir/ritonavir or atazanavir/ritonavir).
O: Time to clinical response was not significantly different between the groups. On day 14, 66.7% of interferon group were discharged while only 43.6% of the control group were discharged. 28-day overall mortality was significantly lower in the interferon group compared to the control group. Early administration significantly reduced mortality.
Strengths: First study regarding use of interferon B-1a in the treatment of COVID-19 and utilized a randomized control trial protocol.
Weaknesses: This study included patients from general, intermediate, and intensive care units during recruitment. The differences in the severity of the patients could influence the results.
Conclusion: Interferon B-1a significantly increased discharge rate on day 14 and decreased 28-day mortality. There was no change in time to clinical response. Survival rate was increased with early administration of interferon B-1a.
Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital
Journal: Nature Communications
Journal: Nature Communications
Link: https://www.nature.com/articles/s41467-020-17318-x
P: 578 health care workers from Hospital Clinic of Barcelona
I: No intervention
C: No control
O: 54 participants were seropositive for IgM and/or IgG and/or IgA against SARS-CoV-2. Of the 39 health care workers with a previous diagnosis of COVID-19, 6 did not have antibodies present. 11 of the 54 participants with antibodies did not have any COVID-19 symptoms in the previous months. 21 of the 54 participants with antibodies had not been diagnosed with COVID-19. Overall, 65 participants had a positive rRT-PCR in the past, at present, or a positive antibody response indicating that the prevalence of SARS-CoV-2 was 11.2% in this population.
Strengths: First study reporting seroprevalence of antibodies against SARS-CoV-2 among a representative sample of healthcare workers in a high burden area.
Weaknesses: By defining seroprevalence as any of IgM, IgG, or IgA, the specificity is reduced. Additionally, because the data was collected over a 12 day period it is more difficult to truly assess the prevalence as the prevalence must be interpreted as the average over the 12 days.
Conclusion: The seroprevalence of antibodies to SARS-CoV-2 was lower than expected. Most participants with confirmed COVID-19 diagnosis had antibodies present. There was a fairly significant number of participants with positive antibodies despite a previous diagnosis of COVID-19, highlighting the importance of testing individuals with high exposures to reduce hospital acquired infections.
P: 578 health care workers from Hospital Clinic of Barcelona
I: No intervention
C: No control
O: 54 participants were seropositive for IgM and/or IgG and/or IgA against SARS-CoV-2. Of the 39 health care workers with a previous diagnosis of COVID-19, 6 did not have antibodies present. 11 of the 54 participants with antibodies did not have any COVID-19 symptoms in the previous months. 21 of the 54 participants with antibodies had not been diagnosed with COVID-19. Overall, 65 participants had a positive rRT-PCR in the past, at present, or a positive antibody response indicating that the prevalence of SARS-CoV-2 was 11.2% in this population.
Strengths: First study reporting seroprevalence of antibodies against SARS-CoV-2 among a representative sample of healthcare workers in a high burden area.
Weaknesses: By defining seroprevalence as any of IgM, IgG, or IgA, the specificity is reduced. Additionally, because the data was collected over a 12 day period it is more difficult to truly assess the prevalence as the prevalence must be interpreted as the average over the 12 days.
Conclusion: The seroprevalence of antibodies to SARS-CoV-2 was lower than expected. Most participants with confirmed COVID-19 diagnosis had antibodies present. There was a fairly significant number of participants with positive antibodies despite a previous diagnosis of COVID-19, highlighting the importance of testing individuals with high exposures to reduce hospital acquired infections.
June 8- 12, 2020
ASSOCIATION OF NONINVASIVE OXYGENATION STRATEGIES WITH ALL-CAUSE MORTALITY IN ADULTS WITH ACUTE HYPOXEMIC RESPIRATORY FAILURE
JOURNAL: JAMA
JOURNAL: JAMA
Link: : https://jamanetwork.com/journals/jama/fullarticle/2767025
Summary
P: Adults with acute hypoxemic respiratory failure requiring oxygen therapy as a results of COVID-19 infection
I: Use of non-invasive oxygenation strategies including high-flow nasal oxygen, face mask noninvasive ventilation, helmet noninvasive ventilation
C: Standard oxygen therapy
O: Use of non-invasive ventilation techniques including helmet noninvasive ventilation, face mask noninvasive ventilation and high-flow nasal oxygen was associated with lower mortality and decreased risk of endotracheal intubation compared to standard oxygen treatment.
Strengths: The main strength of the study was that its meta-analysis design allowed authors to examine results from twenty-five randomized control trials involving 3804 patients. This makes the results reliable and applicable to a large variety of individuals. Moreover, they were able to compare multiple options of non-invasive oxygenation strategies.
Limitations: Given the nature of the studies, blinding was not possible. The authors report that because of this, the risk of bias is high because clinicians may have been more likely to provide certain care to the treatment or control groups.
Conclusions: This study offers a viable method to decrease the high level of morbidity and mortality occurring due to COVID-19. The large sample size from many different studies suggests that noninvasive oxygenation techniques are a promising option for decreasing risk of death and should be explored further.
Summary
P: Adults with acute hypoxemic respiratory failure requiring oxygen therapy as a results of COVID-19 infection
I: Use of non-invasive oxygenation strategies including high-flow nasal oxygen, face mask noninvasive ventilation, helmet noninvasive ventilation
C: Standard oxygen therapy
O: Use of non-invasive ventilation techniques including helmet noninvasive ventilation, face mask noninvasive ventilation and high-flow nasal oxygen was associated with lower mortality and decreased risk of endotracheal intubation compared to standard oxygen treatment.
Strengths: The main strength of the study was that its meta-analysis design allowed authors to examine results from twenty-five randomized control trials involving 3804 patients. This makes the results reliable and applicable to a large variety of individuals. Moreover, they were able to compare multiple options of non-invasive oxygenation strategies.
Limitations: Given the nature of the studies, blinding was not possible. The authors report that because of this, the risk of bias is high because clinicians may have been more likely to provide certain care to the treatment or control groups.
Conclusions: This study offers a viable method to decrease the high level of morbidity and mortality occurring due to COVID-19. The large sample size from many different studies suggests that noninvasive oxygenation techniques are a promising option for decreasing risk of death and should be explored further.
SWABS COLLECTED BY PATIENTS OR HEALTH CARE WORKERS FOR SARS-COV-2 TESTING
JOURNAL: NEJM
JOURNAL: NEJM
Link: https://www.nejm.org/doi/full/10.1056/NEJMc2016321?query=featured_coronavirus
Summary
P: 530 patients with symptoms indicative of upper respiratory infection who were seen in any one of five ambulatory clinics in the Puget Sound region of Washington.
I: Patients asked to collect tongue, nasal, and mid-turbinate samples, in that order. A nasopharyngeal sample was then collected from the patient by a health care worker. All samples were submitted to a reference laboratory for reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing that yielded qualitative results (positive or negative) and cycle threshold (Ct) values for positive samples only
C: The nasopharyngeal sample collected by the healthcare worker served as the control as that had been already proven as the most effective manner to test for SARS-CoV-2 and was used to compare the validity of the results from the tongue, nasal, and mid-turbinate samples.
O: The primary outcome for the study was to determine whether the sensitivities of the non-nasopharyngeal swabs collected by the patients themselves were significantly greater than 90%.
Strengths: The analysis included a large sample size for the patient population and multiple non-nasopharyngeal sampling methods in order to further prove more than one effective way to test for SARS-CoV-2.
Limitations: The analysis was cross-sectional, performed in a single geographic region, and limited to single comparisons with the results of nasopharyngeal sampling, which is not a perfect standard test. The analysis was also not randomized.
Conclusions: The results showed that when compared to the nasopharyngeal testing the estimated sensitivities of the tongue samples was 89.8%, nasal samples was 94.0%, and mid-turbinate samples collected by the patients was 96.2%. Although the estimated sensitivities of the nasal and mid-turbinate samples were greater than 90%, all the confidence intervals for the sensitivity of the samples collected by the patients contained 90%. Despite this lack of statistical significance, both the nasal and mid-turbinate samples may be clinically acceptable on the basis of estimated sensitivities above 90% and the 87%. Overall, this study showed the clinical usefulness of tongue, nasal, or mid-turbinate samples collected by patients as compared with nasopharyngeal samples collected by health care workers for the diagnosis of Covid-19. Adoption of techniques for sampling by patients can reduce PPE use and provide a more comfortable patient experience.
Summary
P: 530 patients with symptoms indicative of upper respiratory infection who were seen in any one of five ambulatory clinics in the Puget Sound region of Washington.
I: Patients asked to collect tongue, nasal, and mid-turbinate samples, in that order. A nasopharyngeal sample was then collected from the patient by a health care worker. All samples were submitted to a reference laboratory for reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing that yielded qualitative results (positive or negative) and cycle threshold (Ct) values for positive samples only
C: The nasopharyngeal sample collected by the healthcare worker served as the control as that had been already proven as the most effective manner to test for SARS-CoV-2 and was used to compare the validity of the results from the tongue, nasal, and mid-turbinate samples.
O: The primary outcome for the study was to determine whether the sensitivities of the non-nasopharyngeal swabs collected by the patients themselves were significantly greater than 90%.
Strengths: The analysis included a large sample size for the patient population and multiple non-nasopharyngeal sampling methods in order to further prove more than one effective way to test for SARS-CoV-2.
Limitations: The analysis was cross-sectional, performed in a single geographic region, and limited to single comparisons with the results of nasopharyngeal sampling, which is not a perfect standard test. The analysis was also not randomized.
Conclusions: The results showed that when compared to the nasopharyngeal testing the estimated sensitivities of the tongue samples was 89.8%, nasal samples was 94.0%, and mid-turbinate samples collected by the patients was 96.2%. Although the estimated sensitivities of the nasal and mid-turbinate samples were greater than 90%, all the confidence intervals for the sensitivity of the samples collected by the patients contained 90%. Despite this lack of statistical significance, both the nasal and mid-turbinate samples may be clinically acceptable on the basis of estimated sensitivities above 90% and the 87%. Overall, this study showed the clinical usefulness of tongue, nasal, or mid-turbinate samples collected by patients as compared with nasopharyngeal samples collected by health care workers for the diagnosis of Covid-19. Adoption of techniques for sampling by patients can reduce PPE use and provide a more comfortable patient experience.
Universal Testing for COVID-19 in Essential Orthopaedic Surgery Reveals a High Percentage of Asymptomatic Infections
Journal: The Journal of Bone and Joint Surgery
Journal: The Journal of Bone and Joint Surgery
Link: https://pubmed-ncbi-nlm-nih-gov.ezproxy.augusta.edu/32516279/
Summary
P: Patients undergoing orthopedic surgery
I: Nasopharyngeal RT-PCR testing for COVID-19
C: Symptomatic patients with COVID-19
O: Positive COVID-19 test result
Strengths: Universal testing of an essentially random group of patients gives this study a more representative view of asymptomatic cases.
Limitations: Small sample size may limit generalizability
Conclusions:
From the article: “A protocol for universal testing of all orthopaedic surgery admissions at 1 hospital in New York City during a 3-week period revealed a high rate of COVID-19 infections. Importantly, the majority of these patients were asymptomatic. Using chest radiography did not significantly improve the negative predictive value of screening. These results have important implications as hospitals anticipate the resumption of elective surgical procedures.” While this study had a small sample size, the results lend further evidence to the theory that a large portion of people with COVID-19 are asymptomatic. Assuming this is true, questionnaire and temperature screening would not necessarily be effective at identifying COVID-19 infections.
Summary
P: Patients undergoing orthopedic surgery
I: Nasopharyngeal RT-PCR testing for COVID-19
C: Symptomatic patients with COVID-19
O: Positive COVID-19 test result
Strengths: Universal testing of an essentially random group of patients gives this study a more representative view of asymptomatic cases.
Limitations: Small sample size may limit generalizability
Conclusions:
From the article: “A protocol for universal testing of all orthopaedic surgery admissions at 1 hospital in New York City during a 3-week period revealed a high rate of COVID-19 infections. Importantly, the majority of these patients were asymptomatic. Using chest radiography did not significantly improve the negative predictive value of screening. These results have important implications as hospitals anticipate the resumption of elective surgical procedures.” While this study had a small sample size, the results lend further evidence to the theory that a large portion of people with COVID-19 are asymptomatic. Assuming this is true, questionnaire and temperature screening would not necessarily be effective at identifying COVID-19 infections.
A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19
Journal: NEJM
Journal: NEJM
Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2016638
Summary:
P: The population included 821 participants who were asymptomatic but had undergone moderate-risk exposure (face mask but no eye shield) or high-risk exposure (no face mask nor eye shield) to an individual with confirmed COVID-19. They were randomly assigned to the intervention group (414 participants) and the control group (407 participants).
I: The intervention dosing regimen was started within 4 days of exposure. The first dose was 800 mg. of hydroxychloroquine, with a second dose of 600 mg. given 6 to 8 hours later. Then, 600 mg. were taken daily for 4 more days. Thus, the dosing regimen lasted 5 days total.
C: Folate tablets were used as a placebo, and the dosing regimen was identical to the intervention.
O: The primary outcome was “symptomatic illness confirmed by a positive molecular assay or, if testing was unavailable, Covid-19 related symptoms.”
Strengths: Peer-reviewed. Randomized, double-blind, placebo-controlled trial with participants from across the U.S. and Canada. Demographics and baseline medical status were well-balanced.
Limitations: Testing was limited at the time of the study; thus, participants whose symptoms matched a COVID-19 presentation were presumed to be SARS-CoV-2 positive. The population used was younger (median age around 40 years old) and healthier as no high-risk groups were included.
Conclusion: 11.8% of the hydroxychloroquine group developed illness compatible with COVID-19, while 14.3% of the control group did. However, the p-value was 0.35, so the difference was not significant. In addition, more side effects were noted in the hydroxychloroquine group (40.1%) versus the control group (16.8%), with the most common side effects being nausea, loose stools, and abdominal discomfort. However, no severe side effects or cardiac arrhythmias were reported, though this could be due to the population being healthier and younger. Thus, one cannot deny the possibility of severe side effects in more at-risk populations. In any case, prophylaxis with hydroxychloroquine did not significantly prevent SARS-CoV-2 infection after exposure to a confirmed COVID-19 individual.
Summary:
P: The population included 821 participants who were asymptomatic but had undergone moderate-risk exposure (face mask but no eye shield) or high-risk exposure (no face mask nor eye shield) to an individual with confirmed COVID-19. They were randomly assigned to the intervention group (414 participants) and the control group (407 participants).
I: The intervention dosing regimen was started within 4 days of exposure. The first dose was 800 mg. of hydroxychloroquine, with a second dose of 600 mg. given 6 to 8 hours later. Then, 600 mg. were taken daily for 4 more days. Thus, the dosing regimen lasted 5 days total.
C: Folate tablets were used as a placebo, and the dosing regimen was identical to the intervention.
O: The primary outcome was “symptomatic illness confirmed by a positive molecular assay or, if testing was unavailable, Covid-19 related symptoms.”
Strengths: Peer-reviewed. Randomized, double-blind, placebo-controlled trial with participants from across the U.S. and Canada. Demographics and baseline medical status were well-balanced.
Limitations: Testing was limited at the time of the study; thus, participants whose symptoms matched a COVID-19 presentation were presumed to be SARS-CoV-2 positive. The population used was younger (median age around 40 years old) and healthier as no high-risk groups were included.
Conclusion: 11.8% of the hydroxychloroquine group developed illness compatible with COVID-19, while 14.3% of the control group did. However, the p-value was 0.35, so the difference was not significant. In addition, more side effects were noted in the hydroxychloroquine group (40.1%) versus the control group (16.8%), with the most common side effects being nausea, loose stools, and abdominal discomfort. However, no severe side effects or cardiac arrhythmias were reported, though this could be due to the population being healthier and younger. Thus, one cannot deny the possibility of severe side effects in more at-risk populations. In any case, prophylaxis with hydroxychloroquine did not significantly prevent SARS-CoV-2 infection after exposure to a confirmed COVID-19 individual.
ARTIFICIAL INTELLIGENCE-ENABLED RAPID DIAGNOSIS OF PATIENTS WITH COVID-19
JOURNAL: NATURE MEDICINE
JOURNAL: NATURE MEDICINE
Link: https://doi.org/10.1038/s41591-020-0931-3
Summary
P: This study included 905 patients tested by real-time and next-gen RT–PCR, in total 419 (46%) tested positive for SARS-CoV-2.
I: Can an AI system be developed to diagnosis COVID-19 using only chest CT and clinical data?
C: Evaluated the AI diagnostic tool on the test set (279 patients) and compared performance to a thoracic radiologist with 10 years of experience and a thoracic radiology fellow
O: Proposed joint AI algorithm combining CT images + clinical patient history performed with a sensitivity & specificity of 84% & 83%, compared to senior thoracic radiologist (75% sensitivity, 95% specificity), and a thoracic radiology fellow (56%, 90%).
Strengths: A convolutional neural network (CNN) was used to extract features from chest CT images and was combined with clinical patient features for creating predictions. Large patient populations. Ground truth labels (COVID-19 status) for CT data was using RT-PCR. Fully patient independent randomly split dataset into a training set (534 cases; 242 COVID+; 292 COVID−), a tuning set (92 cases; 43 COVID+; 49 COVID−) and a test set (279 cases; 134 COVID+; 145 COVID-19−). This helps the results be unbiased, realistic application to new patients.
Limitations: The joint Chest CT CNN + patient history AI model performed with higher sensitivity than radiologist/fellow (by 10+%) but had a lower specificity (by 5+%). Therefore, human radiologists have a greater “rule-in” potential, meaning lower False-Positive Rate (FPR) and greater Positive Predictive Value (PPV) than the AI model.
Conclusion: The AI model shows promise for helping “rule-out” CT scans (with high sensitivity), which could provide clinical value in pandemics by reducing physician burden.
Summary
P: This study included 905 patients tested by real-time and next-gen RT–PCR, in total 419 (46%) tested positive for SARS-CoV-2.
I: Can an AI system be developed to diagnosis COVID-19 using only chest CT and clinical data?
C: Evaluated the AI diagnostic tool on the test set (279 patients) and compared performance to a thoracic radiologist with 10 years of experience and a thoracic radiology fellow
O: Proposed joint AI algorithm combining CT images + clinical patient history performed with a sensitivity & specificity of 84% & 83%, compared to senior thoracic radiologist (75% sensitivity, 95% specificity), and a thoracic radiology fellow (56%, 90%).
Strengths: A convolutional neural network (CNN) was used to extract features from chest CT images and was combined with clinical patient features for creating predictions. Large patient populations. Ground truth labels (COVID-19 status) for CT data was using RT-PCR. Fully patient independent randomly split dataset into a training set (534 cases; 242 COVID+; 292 COVID−), a tuning set (92 cases; 43 COVID+; 49 COVID−) and a test set (279 cases; 134 COVID+; 145 COVID-19−). This helps the results be unbiased, realistic application to new patients.
Limitations: The joint Chest CT CNN + patient history AI model performed with higher sensitivity than radiologist/fellow (by 10+%) but had a lower specificity (by 5+%). Therefore, human radiologists have a greater “rule-in” potential, meaning lower False-Positive Rate (FPR) and greater Positive Predictive Value (PPV) than the AI model.
Conclusion: The AI model shows promise for helping “rule-out” CT scans (with high sensitivity), which could provide clinical value in pandemics by reducing physician burden.
CLINICAL CHARACTERISTICS OF 58 CHILDREN WITH A PEDIATRIC INFLAMMATORY MULTISYSTEM SYNDROME TEMPORALLY ASSOCIATED WITH SARS-COV-2
JOURNAL: JAMA
JOURNAL: JAMA
Link: https://jamanetwork.com/journals/jama/fullarticle/2767209
P: 58 children from 8 hospitals in England admitted between March 23 and May 16, 2020
I: Children were included who met the UK, CDC, or WHO definitions for PIMS-TS, without requiring proof of SARS-CoV-2 exposure.
C: Some clinical features of the children that met the criteria for PIMS-TS, had overlapping features of Kawasaki Disease and Kawasaki Disease shock syndrome. Clinical features of cases were compared against features of patients with KD and KD shock syndrome seen between 2002-2019 at Rady Children’s Hospital San Diego. Clinical features were also compared against features of children with toxic shock syndrome from the PERFORM and EUCLIDS studies of febrile children in the European Union who were seen between 2012 and 2020.
O: The patients’ clinical characteristics, SARS-CoV-2 test results, laboratory investigations, microbiological and virological investigations, and clinical courses following admission were reported as outcomes.
Limitations: This study was based on retrospective data collection from a number of hospitals, therefore investigations and management were individualized by the center and patient rather than following a standardized protocol. Also PCR testing of stool was not routinely done and therefore there are only results for a small number of children.
Strengths: Clinical manifestations and lab values of patients with PIMS-TS are able to be compared to past presentations of KD and KD shock syndrome.
Conclusions: The study provides evidence that there is a wide spectrum of signs, symptoms, and disease severity associated with PIMS-TS. The comparison of patients with KD and KD shock syndrome provides insights into the syndrome, and suggests that the disorder differs from other pediatric inflammatory disorders. Also, since the cases of PIMS-TS have emerged in the wake of a global pandemic, a link with SARS-CoV-2 is likely.
P: 58 children from 8 hospitals in England admitted between March 23 and May 16, 2020
I: Children were included who met the UK, CDC, or WHO definitions for PIMS-TS, without requiring proof of SARS-CoV-2 exposure.
C: Some clinical features of the children that met the criteria for PIMS-TS, had overlapping features of Kawasaki Disease and Kawasaki Disease shock syndrome. Clinical features of cases were compared against features of patients with KD and KD shock syndrome seen between 2002-2019 at Rady Children’s Hospital San Diego. Clinical features were also compared against features of children with toxic shock syndrome from the PERFORM and EUCLIDS studies of febrile children in the European Union who were seen between 2012 and 2020.
O: The patients’ clinical characteristics, SARS-CoV-2 test results, laboratory investigations, microbiological and virological investigations, and clinical courses following admission were reported as outcomes.
Limitations: This study was based on retrospective data collection from a number of hospitals, therefore investigations and management were individualized by the center and patient rather than following a standardized protocol. Also PCR testing of stool was not routinely done and therefore there are only results for a small number of children.
Strengths: Clinical manifestations and lab values of patients with PIMS-TS are able to be compared to past presentations of KD and KD shock syndrome.
Conclusions: The study provides evidence that there is a wide spectrum of signs, symptoms, and disease severity associated with PIMS-TS. The comparison of patients with KD and KD shock syndrome provides insights into the syndrome, and suggests that the disorder differs from other pediatric inflammatory disorders. Also, since the cases of PIMS-TS have emerged in the wake of a global pandemic, a link with SARS-CoV-2 is likely.
Povidone-Iodine Use in Sinonasal and Oral Cavities: A Review of Safety in the COVID-19 Era
Journal: Ear, Nose & Throat Journal
Journal: Ear, Nose & Throat Journal
Link: https://journals.sagepub.com/doi/10.1177/0145561320932318
Summary:
P: Patients receiving povidone-iodine
I: Topical povidone-iodine exposure in the nasal and oral cavity
C: Participants who did not receive povidone-iodine
O: Changes in oral and nasal epithelia
Strengths: The reviewers examine data from a wide variety of studies, providing a comprehensive overview of the current research on povidone-iodine.
Limitations: The reviewed studies utilized different populations, making the data more difficult to integrate.
Conclusions:
From the article: “Povidone-iodine can safely be used in the nose at concentrations up to 1.25% and in the mouth at concentrations up to 2.5% for up to 5 months. Povidone-iodine rapidly inactivates coronaviruses, including SARS and MERS, when applied for as little as 15 seconds. There is optimism that PVP-I can inactivate SARS-CoV-2, but in vitro efficacy has not yet been demonstrated.” This review concludes that povidone-iodine is safe to use for prolonged periods of time. Furthermore, it suggests that povidone-iodine could be effective against SARS-CoC-2 based on its effectiveness against similar coronaviruses.
Summary:
P: Patients receiving povidone-iodine
I: Topical povidone-iodine exposure in the nasal and oral cavity
C: Participants who did not receive povidone-iodine
O: Changes in oral and nasal epithelia
Strengths: The reviewers examine data from a wide variety of studies, providing a comprehensive overview of the current research on povidone-iodine.
Limitations: The reviewed studies utilized different populations, making the data more difficult to integrate.
Conclusions:
From the article: “Povidone-iodine can safely be used in the nose at concentrations up to 1.25% and in the mouth at concentrations up to 2.5% for up to 5 months. Povidone-iodine rapidly inactivates coronaviruses, including SARS and MERS, when applied for as little as 15 seconds. There is optimism that PVP-I can inactivate SARS-CoV-2, but in vitro efficacy has not yet been demonstrated.” This review concludes that povidone-iodine is safe to use for prolonged periods of time. Furthermore, it suggests that povidone-iodine could be effective against SARS-CoC-2 based on its effectiveness against similar coronaviruses.
June 1-5 2020
Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children’s Hospital in New York City, New York
Journal: JAMA
Journal: JAMA
Link: https://jamanetwork.com/journals/jamapediatrics/fullarticle/2766920
Summary:
P: Children and adolescents under the age of 21 who tested positive for COVID-19
I: Standard treatment for COVID-19
C: Average outcomes for children with COVID-19
O: Requirement for mechanical ventilation
Strengths: The study was able to examine the COVID-19 symptoms of a wide variety of children.
Limitations: The small sample size and large Hispanic population of the study may limit the study’s generalizability.
Conclusions: From the article: “As community transmission of SARS-CoV-2 continues, hospitals must be alert to variable presentations of COVID-19, test liberally, attempt early risk stratification of patient populations, and have well-established clinical and IPC protocols. Therapeutic considerations need to consider the risk of toxicity, control of antiviral replication, and early recognition and management of immune dysregulation.”
While this study was relatively small, it gives some insight into how COVID-19 may present in pediatric populations. One interesting result found by the study was that, while obese patients were at greater risk for severe symptoms, infants and immunocompromised patients were not.
Summary:
P: Children and adolescents under the age of 21 who tested positive for COVID-19
I: Standard treatment for COVID-19
C: Average outcomes for children with COVID-19
O: Requirement for mechanical ventilation
Strengths: The study was able to examine the COVID-19 symptoms of a wide variety of children.
Limitations: The small sample size and large Hispanic population of the study may limit the study’s generalizability.
Conclusions: From the article: “As community transmission of SARS-CoV-2 continues, hospitals must be alert to variable presentations of COVID-19, test liberally, attempt early risk stratification of patient populations, and have well-established clinical and IPC protocols. Therapeutic considerations need to consider the risk of toxicity, control of antiviral replication, and early recognition and management of immune dysregulation.”
While this study was relatively small, it gives some insight into how COVID-19 may present in pediatric populations. One interesting result found by the study was that, while obese patients were at greater risk for severe symptoms, infants and immunocompromised patients were not.
EFFECTS OF NON-PHARMACEUTICAL INTERVENTIONS ON COVID-19 CASES, DEATHS, AND DEMAND FOR HOSPITAL SERVICES IN THE UK: A MODELING STUDY
Journal: The Lancet
Journal: The Lancet
LINK: https://www.thelancet.com/pdfs/journals/lanpub/PIIS2468-2667(20)30133-X.pdf
Summary
P: This model assumes the population to be all individuals susceptible to COVID-19 infection in the UK. In the model, the individuals enter exposed state upon effective contact with an infectious person and become infectious with either a subclinical infection or a preclinical infection followed by a clinical infection. After recovery, the model assumes the individual can not be re-infected.
I: Intervention scenarios include: school closures, physical distancing, shielding of people above age 70, self-isolation of symptomatic individuals, lock-down and a combinations of the aforementioned.
C: A lack of interventions for prevention of spread.
O: The primary estimated outcomes are projected impact of each intervention on new cases over time, number of patients requiring intensive care, mortality and impact on basic reproductive number (R0). The results show that each intervention on its own was not sufficient for preventing health care demand from exceeding health systems capacity. Though the combination of interventions was more effective at reducing R0, this scenario also was unable to bring R0, to below 1. Only intensive interventions such as lock down for a majority of the coming year were sufficient to bring the basic reproductive to at or near 1.
Strengths: The analysis models a large population of 66.4 million and is able to look at a wide range of possibilities including the impact of each intervention individually as well as the impact of a combination of interventions.
Limitations: The primary limitations are the number of assumptions involved in the model. One of them is that individuals can not be re-infected after recovering from the disease though this has been disproved. The model also assumes that asymptomatic individuals are less infectious than symptomatic individuals and that isolation occurs based on symptom presence. In reality, asymptomatic infections are key in ongoing transmission. Because of some of these assumptions, the model can not fully simulate our current real life situation. Another limitation for us is that the study is based on the United Kindom’s population so it can not simulate the scenario in the USA. Still, the conclusions may be applicable.
Conclusions: This study suggests that implementing the most stringent social distancing measures for the remainder of the year is necessary to prevent exceeding healthcare capacity and high mortality from the virus.
Summary
P: This model assumes the population to be all individuals susceptible to COVID-19 infection in the UK. In the model, the individuals enter exposed state upon effective contact with an infectious person and become infectious with either a subclinical infection or a preclinical infection followed by a clinical infection. After recovery, the model assumes the individual can not be re-infected.
I: Intervention scenarios include: school closures, physical distancing, shielding of people above age 70, self-isolation of symptomatic individuals, lock-down and a combinations of the aforementioned.
C: A lack of interventions for prevention of spread.
O: The primary estimated outcomes are projected impact of each intervention on new cases over time, number of patients requiring intensive care, mortality and impact on basic reproductive number (R0). The results show that each intervention on its own was not sufficient for preventing health care demand from exceeding health systems capacity. Though the combination of interventions was more effective at reducing R0, this scenario also was unable to bring R0, to below 1. Only intensive interventions such as lock down for a majority of the coming year were sufficient to bring the basic reproductive to at or near 1.
Strengths: The analysis models a large population of 66.4 million and is able to look at a wide range of possibilities including the impact of each intervention individually as well as the impact of a combination of interventions.
Limitations: The primary limitations are the number of assumptions involved in the model. One of them is that individuals can not be re-infected after recovering from the disease though this has been disproved. The model also assumes that asymptomatic individuals are less infectious than symptomatic individuals and that isolation occurs based on symptom presence. In reality, asymptomatic infections are key in ongoing transmission. Because of some of these assumptions, the model can not fully simulate our current real life situation. Another limitation for us is that the study is based on the United Kindom’s population so it can not simulate the scenario in the USA. Still, the conclusions may be applicable.
Conclusions: This study suggests that implementing the most stringent social distancing measures for the remainder of the year is necessary to prevent exceeding healthcare capacity and high mortality from the virus.
Antibody responses to SARS-CoV-2 in patients with COVID-19
Journal: Nature Medicine
Journal: Nature Medicine
Link: https://www.nature.com/articles/s41591-020-0897-1#Sec12
Summary
P: 285 patients with confirmed COVID-19 (by means of RT-PCR assays) from three designated hospitals in Chongqing, a province-level municipality adjacent to Hubei Province.
I: Serum samples were obtained from each patient with a clear record of symptom onset (n=262), with 70 patients having sequential samples available, leading to a total of 363 serum samples included in the analysis.
C: The precision and reproducibility of the MCLIA kits were first evaluated by the National Institutes for Food and Drug Control. Also, 30 serum samples from COVID-19 positive patients showing different titers of IgG and IGM were tested in three independent experiments. The coefficient of variation (CV) was used to evaluate the precision of the assay. Lastly, different batches of the diagnostic kit were evaluated on 46 separate COVID-19 positive serum samples -- the reproducibility was calculated based on these results.
O: The primary outcome was positive rates of virus-specific IgG and IgM versus days after symptom onset in 363 serum samples.
Strengths: The proportion of patients with positive virus specific IgG reach 100% approximately 17-19 days after symptom onset.
Limitations: The study did not test samples for virus neutralization, so the neutralizing effects of the antibodies are unknown. Also, it is difficult to assess the association between antibody response and clinical course due to the small sample size of patients in severe and critical conditions.
Conclusions: The proportion of patients with positive virus-specific IgG reached approximately 100% about 17-19 days after symptom onset, and the proportion of patients with positive virus-specific IgM reached a peak of 94.1% approximately 20-22 days after symptom onset. The research group was also able to follow 63 COVID-19 positive patients and collect serum samples at 3 day intervals. The overall seroconversion rate among these patients was 96.3% (a mother and daughter maintained IgG and IgM negative status during hospitalization).
The group finally investigated the usefulness of serum antibody testing in a cluster of 164 close contacts of patients with a known COVID-19 infection. Of the 164, sixteen individuals were confirmed to be infected with COVID-19 by RT-PCR, with three cases reporting no symptoms. Those sixteen confirmed cases by RT-PCR also tested positive for virus-specific IgG and/or IgM, and seven of the 148 who had negative RT-PCR results actually had positive virus-specific IgG and/or IgM. The data shows that serum testing for virus-specific antibodies could be useful in the diagnosis of suspected cases with negative RT-PCR results and in the surveillance of close contact infection.
Summary
P: 285 patients with confirmed COVID-19 (by means of RT-PCR assays) from three designated hospitals in Chongqing, a province-level municipality adjacent to Hubei Province.
I: Serum samples were obtained from each patient with a clear record of symptom onset (n=262), with 70 patients having sequential samples available, leading to a total of 363 serum samples included in the analysis.
C: The precision and reproducibility of the MCLIA kits were first evaluated by the National Institutes for Food and Drug Control. Also, 30 serum samples from COVID-19 positive patients showing different titers of IgG and IGM were tested in three independent experiments. The coefficient of variation (CV) was used to evaluate the precision of the assay. Lastly, different batches of the diagnostic kit were evaluated on 46 separate COVID-19 positive serum samples -- the reproducibility was calculated based on these results.
O: The primary outcome was positive rates of virus-specific IgG and IgM versus days after symptom onset in 363 serum samples.
Strengths: The proportion of patients with positive virus specific IgG reach 100% approximately 17-19 days after symptom onset.
Limitations: The study did not test samples for virus neutralization, so the neutralizing effects of the antibodies are unknown. Also, it is difficult to assess the association between antibody response and clinical course due to the small sample size of patients in severe and critical conditions.
Conclusions: The proportion of patients with positive virus-specific IgG reached approximately 100% about 17-19 days after symptom onset, and the proportion of patients with positive virus-specific IgM reached a peak of 94.1% approximately 20-22 days after symptom onset. The research group was also able to follow 63 COVID-19 positive patients and collect serum samples at 3 day intervals. The overall seroconversion rate among these patients was 96.3% (a mother and daughter maintained IgG and IgM negative status during hospitalization).
The group finally investigated the usefulness of serum antibody testing in a cluster of 164 close contacts of patients with a known COVID-19 infection. Of the 164, sixteen individuals were confirmed to be infected with COVID-19 by RT-PCR, with three cases reporting no symptoms. Those sixteen confirmed cases by RT-PCR also tested positive for virus-specific IgG and/or IgM, and seven of the 148 who had negative RT-PCR results actually had positive virus-specific IgG and/or IgM. The data shows that serum testing for virus-specific antibodies could be useful in the diagnosis of suspected cases with negative RT-PCR results and in the surveillance of close contact infection.
Clinical characteristics and outcomes in people living with HIV hospitalized for COVID-19
Journal: Clinical Infectious Diseases
Journal: Clinical Infectious Diseases
URL: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa635/5848754
Summary:
P: The population included 31 HIV positive patients who were also diagnosed with COVID-19. Included patients were hospitalized between March 15th and April 15th, 2020 at a “large tertiary care medical center” in New York City. All patients were taking antiretroviral therapy and virally suppressed when they were admitted.
I: No intervention
C: No control
O: The primary outcome was the status of the patient at the time of analysis—deceased, ongoing hospitalization, or discharged.
Strengths: Peer-reviewed. Data taken from institutional HIV and COVID-19 registries. “Largest case series to date describing the clinical characteristics and outcomes” of a hospitalized population of HIV positive patients diagnosed with COVID-19.
Limitations: Small sample size. A comparison to non-HIV patients was not present due to difficulties with matching. Human error when inputting medical records cannot be excluded.
Conclusion: At the time of analysis, 8 patients died, 21 were discharged, and 2 were still hospitalized. All patients were virally suppressed; moreover, 80% of patients had a CD4+ T cell count of >200 cells/ul. Patient clinical course was classified as follows: 1 mild, 2 moderate, 21 severe, and 7 critical. The authors concluded that there was not an increased rate of HIV patient hospitalization, as around 1.4% of the study institution’s patients were HIV positive, while the prevalence of HIV in the hospital catchment area is 1.5%. The authors state that “baseline characteristics and outcomes” of the studied population is comparable to non-HIV patients described in larger cohort studies. However, the small sample size in the present study limits this claim. Interestingly, the study institution had not yet admitted a patient with uncontrolled HIV or AIDS. This is surprising considering that around 25% of New York City’s HIV population is not virally suppressed. The authors hypothesize that uncontrolled HIV infection and impaired CD4+ T cell function may inhibit the immune dysregulation and cytokine release caused by SARS-CoV-2. Of course, this assertion cannot be proven based on the present study, but further research is warranted. Moreover, a study on hospitalized HIV patients with COVID-19 using a larger sample size and a multi-center approach is highly desired.
Summary:
P: The population included 31 HIV positive patients who were also diagnosed with COVID-19. Included patients were hospitalized between March 15th and April 15th, 2020 at a “large tertiary care medical center” in New York City. All patients were taking antiretroviral therapy and virally suppressed when they were admitted.
I: No intervention
C: No control
O: The primary outcome was the status of the patient at the time of analysis—deceased, ongoing hospitalization, or discharged.
Strengths: Peer-reviewed. Data taken from institutional HIV and COVID-19 registries. “Largest case series to date describing the clinical characteristics and outcomes” of a hospitalized population of HIV positive patients diagnosed with COVID-19.
Limitations: Small sample size. A comparison to non-HIV patients was not present due to difficulties with matching. Human error when inputting medical records cannot be excluded.
Conclusion: At the time of analysis, 8 patients died, 21 were discharged, and 2 were still hospitalized. All patients were virally suppressed; moreover, 80% of patients had a CD4+ T cell count of >200 cells/ul. Patient clinical course was classified as follows: 1 mild, 2 moderate, 21 severe, and 7 critical. The authors concluded that there was not an increased rate of HIV patient hospitalization, as around 1.4% of the study institution’s patients were HIV positive, while the prevalence of HIV in the hospital catchment area is 1.5%. The authors state that “baseline characteristics and outcomes” of the studied population is comparable to non-HIV patients described in larger cohort studies. However, the small sample size in the present study limits this claim. Interestingly, the study institution had not yet admitted a patient with uncontrolled HIV or AIDS. This is surprising considering that around 25% of New York City’s HIV population is not virally suppressed. The authors hypothesize that uncontrolled HIV infection and impaired CD4+ T cell function may inhibit the immune dysregulation and cytokine release caused by SARS-CoV-2. Of course, this assertion cannot be proven based on the present study, but further research is warranted. Moreover, a study on hospitalized HIV patients with COVID-19 using a larger sample size and a multi-center approach is highly desired.
Cancer outcomes: “Clinical impact of COVID-19 on patients with cancer (CCC19):
a cohort study”
Journal: The Lancet
a cohort study”
Journal: The Lancet
Link: https://doi.org/10.1016/S0140-6736(20)31187-9
Summary
P: Patients (18+ y.o.) with confirmed SARS-CoV-2 and active or previous malignancy from US, Canada, Spain
I: Odds Ratio (OR) of all-cause mortality within 30 days of COVID-19 diagnosis
C: Different traits, demographics, and clinical features
O: Factors associated with increased mortality, determined by logistic regression
Strengths: Public-access data. Investigation into outcomes of patients with cancer and COVID-19; investigated both general COVID risk factors and risk factors unique to patients with cancer.
Limitations: Limited follow-up, only time-point at 30 days. Potential indication/severity confounding by treatment with azithromycin + hydroxychloroquine compared to patients in which disease status does not indicate.
Conclusions: Several factors were associated with increased OR of mortality, including male sex (1.6), smoking (1.6), 2+ comorbidities (4.5), active cancer i.e. progressing vs remission (5.20), treatment with azithromycin + hydroxychloroquine (2.93, see limitations). Factors linked to decreased OR were residence in Canada vs US-NE (0.24) or the US-Midwest vs US-NE (0.50). Traits that were not associated with mortality included race, obesity status, cancer diagnosis, anticancer therapy type, and surgical history.
Summary
P: Patients (18+ y.o.) with confirmed SARS-CoV-2 and active or previous malignancy from US, Canada, Spain
I: Odds Ratio (OR) of all-cause mortality within 30 days of COVID-19 diagnosis
C: Different traits, demographics, and clinical features
O: Factors associated with increased mortality, determined by logistic regression
Strengths: Public-access data. Investigation into outcomes of patients with cancer and COVID-19; investigated both general COVID risk factors and risk factors unique to patients with cancer.
Limitations: Limited follow-up, only time-point at 30 days. Potential indication/severity confounding by treatment with azithromycin + hydroxychloroquine compared to patients in which disease status does not indicate.
Conclusions: Several factors were associated with increased OR of mortality, including male sex (1.6), smoking (1.6), 2+ comorbidities (4.5), active cancer i.e. progressing vs remission (5.20), treatment with azithromycin + hydroxychloroquine (2.93, see limitations). Factors linked to decreased OR were residence in Canada vs US-NE (0.24) or the US-Midwest vs US-NE (0.50). Traits that were not associated with mortality included race, obesity status, cancer diagnosis, anticancer therapy type, and surgical history.
Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study
Journal: BMJ
Journal: BMJ
Link: https://www.bmj.com/content/369/bmj.m2094
Summary
P: 21 patients (aged ≤18 years) with features of Kawasaki disease who were admitted to hospital between 27 April and 11 May 2020 and followed up until discharge by 15 May 2020.
I: All 21 patients received high dose intravenous immunoglobulin after fever for a median duration of 5 days and low dose aspirin. Seven patients of the 21 also received concomitant corticosteroids.
C: N/A
O: The primary outcomes were clinical and biological data, imaging and echocardiographic findings that confirmed a Kawasaki-like state and the effectiveness of the follow up treatment intervention for SARS-CoV-2. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) and blood samples were tested for IgG antibodies to the virus.
Strengths: The inclusion criteria for the patients looked at both laboratory data along with imaging data which strengthen the inclusion of which patients were considered a Kawasaki-like state.
Limitations: Some limitations include potential recruitment bias may have contributed to the high number of patients with Kawasaki-like multisystem inflammatory syndrome admitted to the general pediatric department, the low sample size of included patients, and since Kawasaki-like multisystem inflammatory syndrome might induce immune reactions with multiple antibody production, patients have cross reactive IgG leading to false positive serology results for SARS-CoV-2.
Conclusions: The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. While the included patients had characteristics that differ from classic Kawasaki disease, this differing form appears more commonly among children of African ancestry, with predominant acute gastrointestinal symptoms, hemodynamic instability, and myocarditis. In this study an unusually high proportion of the affected children and adolescents of SARS-CoV-2 had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry. Further studies are needed to explore potential causality.
Summary
P: 21 patients (aged ≤18 years) with features of Kawasaki disease who were admitted to hospital between 27 April and 11 May 2020 and followed up until discharge by 15 May 2020.
I: All 21 patients received high dose intravenous immunoglobulin after fever for a median duration of 5 days and low dose aspirin. Seven patients of the 21 also received concomitant corticosteroids.
C: N/A
O: The primary outcomes were clinical and biological data, imaging and echocardiographic findings that confirmed a Kawasaki-like state and the effectiveness of the follow up treatment intervention for SARS-CoV-2. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) and blood samples were tested for IgG antibodies to the virus.
Strengths: The inclusion criteria for the patients looked at both laboratory data along with imaging data which strengthen the inclusion of which patients were considered a Kawasaki-like state.
Limitations: Some limitations include potential recruitment bias may have contributed to the high number of patients with Kawasaki-like multisystem inflammatory syndrome admitted to the general pediatric department, the low sample size of included patients, and since Kawasaki-like multisystem inflammatory syndrome might induce immune reactions with multiple antibody production, patients have cross reactive IgG leading to false positive serology results for SARS-CoV-2.
Conclusions: The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. While the included patients had characteristics that differ from classic Kawasaki disease, this differing form appears more commonly among children of African ancestry, with predominant acute gastrointestinal symptoms, hemodynamic instability, and myocarditis. In this study an unusually high proportion of the affected children and adolescents of SARS-CoV-2 had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry. Further studies are needed to explore potential causality.
Effect of Convalescent Plasma therapy on Time to Clinical Improvement in PatienTs with Severe and Life-threatening COVID-19
JourNal: JAMA
JourNal: JAMA
Link: https://jamanetwork.com/journals/jama/fullarticle/2766943
Summary:
P: Patients with severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation) COVID-19
I: Convalescent plasma in addition to standard treatment
C: Standard treatment for COVID-19 without convalescent plasma
O: time to clinical improvement (discharge or 2-point reduction on 6 point severity scale) within 28 days, 28 mortality, time to discharge, and rate of negative PCR test results from previously positive patients
Strengths: Randomized multicenter trial
Limitations: The study was terminated early due to a lack of new COVID 19 patients in Wuhan, China
Conclusions:
From the article: “Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.”
While this study was not able to show a significant effect of convalescent plasma, it is important to keep in mind that this study was terminated early with only 101 patients. Because of this, it is not possible to definitively conclude whether convalescent plasma would be beneficial to COVID-19 patients.
Summary:
P: Patients with severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation) COVID-19
I: Convalescent plasma in addition to standard treatment
C: Standard treatment for COVID-19 without convalescent plasma
O: time to clinical improvement (discharge or 2-point reduction on 6 point severity scale) within 28 days, 28 mortality, time to discharge, and rate of negative PCR test results from previously positive patients
Strengths: Randomized multicenter trial
Limitations: The study was terminated early due to a lack of new COVID 19 patients in Wuhan, China
Conclusions:
From the article: “Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.”
While this study was not able to show a significant effect of convalescent plasma, it is important to keep in mind that this study was terminated early with only 101 patients. Because of this, it is not possible to definitively conclude whether convalescent plasma would be beneficial to COVID-19 patients.
Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis
JouRnal: The Lancet
JouRnal: The Lancet
Link: https://www.sciencedirect.com/science/article/pii/S0140673620311429?via%3Dihub
Summary:
P: The systematic review included 172 observational studies. For the meta-analysis, 44 comparative studies were analyzed, totaling 25,967 patients with COVID-19, SARS, or MERS.
I: No intervention
C: No control
O: The primary outcome was “risk of transmission (ie, WHO defined confirmed or probable COVID-19, SARS, or MERS) to people in health-care or non-health-care settings by those infected.”
Strengths: Many studies from a variety of international settings included in the analysis. Rigorous statistical analysis. Peer-reviewed. Per the authors, this is the first paper, to the best of their knowledge, to collate information on the effectiveness of three protective measures against SARS-CoV-2 infection
Limitations: Per the authors, none of the studies were randomized and they were “not always adjusted.” They also cite the possibility of measurement and recall bias in the studies used. In addition, of the 13 papers that study eye protection, only one is on COVID-19, while the rest concern themselves with either MERS or SARS. However, the causative agents of MERS and SARS, MERS-CoV and SARS-CoV respectively, are beta coronaviruses, the same viral family that SARS-CoV-2 belongs to.
Conclusion: Physical distancing of at least 1 m. was found to decrease viral transmission. The benefit was found to increase at distances of 2 m. A similar relationship was noted with mask usage. N95 masks conferred the greatest protection, followed by surgical masks, 12 to 16-layer cotton masks, and other similar masks. The benefit of mask usage was seen in both the health and general public arenas. Only 1 of 13 papers on eye protection focused on SARS-CoV-2 infection, but the results of the other 12 works, which were on beta corona viruses (MERS-CoV and SARS-CoV), suggested an additional protective benefit with eye protection. The authors suggest further research using randomized trials to investigate the effectiveness of different mask types and the optimum physical distance for preventing viral transmission. However, given the rapidly evolving public health crisis we currently find ourselves in, the trends the authors have noted regarding physical distancing, mask usage, and eye protection should be used to guide public health policy until further information becomes available.
Summary:
P: The systematic review included 172 observational studies. For the meta-analysis, 44 comparative studies were analyzed, totaling 25,967 patients with COVID-19, SARS, or MERS.
I: No intervention
C: No control
O: The primary outcome was “risk of transmission (ie, WHO defined confirmed or probable COVID-19, SARS, or MERS) to people in health-care or non-health-care settings by those infected.”
Strengths: Many studies from a variety of international settings included in the analysis. Rigorous statistical analysis. Peer-reviewed. Per the authors, this is the first paper, to the best of their knowledge, to collate information on the effectiveness of three protective measures against SARS-CoV-2 infection
Limitations: Per the authors, none of the studies were randomized and they were “not always adjusted.” They also cite the possibility of measurement and recall bias in the studies used. In addition, of the 13 papers that study eye protection, only one is on COVID-19, while the rest concern themselves with either MERS or SARS. However, the causative agents of MERS and SARS, MERS-CoV and SARS-CoV respectively, are beta coronaviruses, the same viral family that SARS-CoV-2 belongs to.
Conclusion: Physical distancing of at least 1 m. was found to decrease viral transmission. The benefit was found to increase at distances of 2 m. A similar relationship was noted with mask usage. N95 masks conferred the greatest protection, followed by surgical masks, 12 to 16-layer cotton masks, and other similar masks. The benefit of mask usage was seen in both the health and general public arenas. Only 1 of 13 papers on eye protection focused on SARS-CoV-2 infection, but the results of the other 12 works, which were on beta corona viruses (MERS-CoV and SARS-CoV), suggested an additional protective benefit with eye protection. The authors suggest further research using randomized trials to investigate the effectiveness of different mask types and the optimum physical distance for preventing viral transmission. However, given the rapidly evolving public health crisis we currently find ourselves in, the trends the authors have noted regarding physical distancing, mask usage, and eye protection should be used to guide public health policy until further information becomes available.
May 25-29 2020
Promising Results from China: Safety, tolerability, and immunogenicity of a recombinant
adenovirus type-5 vectored COVID-19 vaccine
JOURNAL: THE LANCET
adenovirus type-5 vectored COVID-19 vaccine
JOURNAL: THE LANCET
Link
Summary:
P: The population was 108 participants, all of whom were adults in good health, negative for SARS-CoV-2 infection, and between the ages of 18 and 60 years old. The 108 participants were divided into three groups of 36—low dose, middle dose, and high dose groups.
I: As mentioned above, the participants were divided into three groups based on dosage. Each vial of the vaccine contained 5 x 10^10 viral particles per 0.5 mL. The dosages for the three groups are as follows: 5 x 10^10 viral particles per 0.5 mL for the low dose group (one vial), 1 x 10^11 viral particles per mL for the middle dose group (two vials), and 1.5 x 10^11 viral particles per 1.5 mL for the high dose group (three vials). All vaccine doses were administered intramuscularly.
C: No placebo control was present in the trial.
O: The primary outcome was occurrence of adverse reactions within 7 days of vaccination. Secondary outcomes included abnormal changes in lab values 7 days post-vaccination, as well as adverse events within 28 days of vaccination.
Strengths: The “baseline characteristics” across all three dosage groups were similar. Also, thorough measures were taken to exclude participants infected with SARS-CoV-2 and to prevent infection in those participating in the study. Serological screening, nucleic acid testing, and chest CT’s were used to exclude participants who had been exposed to SARS-CoV-2 during recruitment. Those who were included in the study stayed in a “designated hotel” for 14 days in order to prevent SARS-CoV-2 infection.
Limitations: The sample size is small, though the authors acknowledge this. This is also expected given that this is a phase 1 trial. Moreover, the short duration of follow-up and the lack of a randomized control group limits interpretation of the results. Only 16% of the study participants were older than 50 years; in addition, no participants were more than 60 years old. However, phase 2 of the trial will include participants older than 60 years per the authors.
Conclusion: The Ad5 vectored COVID-19 vaccine was found to be tolerable and immunogenic in the population studied. Most adverse reactions were mild to moderate in severity. The few severe adverse reactions were short-lived and self-limiting. No abnormal changes in lab values were seen. “Specific humoral responses” peaked by day 28, while rapid, specific T-cell responses were noted by day 14 after one shot of vaccine. A majority of all three dosage groups had at least a four-fold increase in receptor-binding domain antibodies by day 28. However, four-fold increases in neutralizing antibodies to live SARS-CoV-2 were less prevalent, as this result was found in 50% of the low dose and middle dose groups and 75% of the high dose group by day 28. It is believed that the decreased response of neutralizing antibodies to the vaccine is due to participants with high pre-existing Ad5 neutralizing antibody titers. Regarding T-cell responses, the three dosage groups had a positive result rate of at least 80% by day 14, though this percentage decreased particularly in low dosage participants who had high pre-existing Ad5 neutralizing antibody titers. Despite interference from pre-existing Ad5 neutralizing antibodies, the results support the safety and immunogenicity of the vaccine. As the vaccine proceeds to phase 2, more will be learned about its efficacy.
Summary:
P: The population was 108 participants, all of whom were adults in good health, negative for SARS-CoV-2 infection, and between the ages of 18 and 60 years old. The 108 participants were divided into three groups of 36—low dose, middle dose, and high dose groups.
I: As mentioned above, the participants were divided into three groups based on dosage. Each vial of the vaccine contained 5 x 10^10 viral particles per 0.5 mL. The dosages for the three groups are as follows: 5 x 10^10 viral particles per 0.5 mL for the low dose group (one vial), 1 x 10^11 viral particles per mL for the middle dose group (two vials), and 1.5 x 10^11 viral particles per 1.5 mL for the high dose group (three vials). All vaccine doses were administered intramuscularly.
C: No placebo control was present in the trial.
O: The primary outcome was occurrence of adverse reactions within 7 days of vaccination. Secondary outcomes included abnormal changes in lab values 7 days post-vaccination, as well as adverse events within 28 days of vaccination.
Strengths: The “baseline characteristics” across all three dosage groups were similar. Also, thorough measures were taken to exclude participants infected with SARS-CoV-2 and to prevent infection in those participating in the study. Serological screening, nucleic acid testing, and chest CT’s were used to exclude participants who had been exposed to SARS-CoV-2 during recruitment. Those who were included in the study stayed in a “designated hotel” for 14 days in order to prevent SARS-CoV-2 infection.
Limitations: The sample size is small, though the authors acknowledge this. This is also expected given that this is a phase 1 trial. Moreover, the short duration of follow-up and the lack of a randomized control group limits interpretation of the results. Only 16% of the study participants were older than 50 years; in addition, no participants were more than 60 years old. However, phase 2 of the trial will include participants older than 60 years per the authors.
Conclusion: The Ad5 vectored COVID-19 vaccine was found to be tolerable and immunogenic in the population studied. Most adverse reactions were mild to moderate in severity. The few severe adverse reactions were short-lived and self-limiting. No abnormal changes in lab values were seen. “Specific humoral responses” peaked by day 28, while rapid, specific T-cell responses were noted by day 14 after one shot of vaccine. A majority of all three dosage groups had at least a four-fold increase in receptor-binding domain antibodies by day 28. However, four-fold increases in neutralizing antibodies to live SARS-CoV-2 were less prevalent, as this result was found in 50% of the low dose and middle dose groups and 75% of the high dose group by day 28. It is believed that the decreased response of neutralizing antibodies to the vaccine is due to participants with high pre-existing Ad5 neutralizing antibody titers. Regarding T-cell responses, the three dosage groups had a positive result rate of at least 80% by day 14, though this percentage decreased particularly in low dosage participants who had high pre-existing Ad5 neutralizing antibody titers. Despite interference from pre-existing Ad5 neutralizing antibodies, the results support the safety and immunogenicity of the vaccine. As the vaccine proceeds to phase 2, more will be learned about its efficacy.
Association of Stay-at-Home Orders With COVID-19 Hospitalizations in 4 States
Research Letter
JOURNAL: JAMA
Research Letter
JOURNAL: JAMA
Link
Summary
P: Four states (Colorado, Minnesota, Ohio, and Virginia) that had at least 7 consecutive days of cumulative hospitalization data for COVID-19 before the stay-at-home order date and at least 17 days following the order date.
I: Stay-at-home order issued by state
C: Each state’s COVID-19 hospitalization data up until the determined effective date of the stay-at-home order was plotted against a best fit exponential growth function. The cumulative hospitalizations after the median effective date were then observed to see if they deviated from the projected exponential growth.
O: Deviation from the best fit exponential growth curve.
Strengths: The deviations from the expected curves for each state are seen at or around the expected median effective date of the stay-at-home orders and these deviations are statistically significant.
Limitations: This analysis assumes that all deviations from the projected hospitalizations are a result of the stay-at-home order. Data was only available for four states.
Conclusions: Prior to enacting stay-at-home orders, each state’s cumulative COVID-19 hospitalization curve favored an exponential function over a linear function. After the median effective date for the orders, the plotted hospitalizations fell out of the 95% prediction bands for the projected exponential growth function -- suggesting that the stay-at-home orders had a significant effect on spread of COVID-19.
Summary
P: Four states (Colorado, Minnesota, Ohio, and Virginia) that had at least 7 consecutive days of cumulative hospitalization data for COVID-19 before the stay-at-home order date and at least 17 days following the order date.
I: Stay-at-home order issued by state
C: Each state’s COVID-19 hospitalization data up until the determined effective date of the stay-at-home order was plotted against a best fit exponential growth function. The cumulative hospitalizations after the median effective date were then observed to see if they deviated from the projected exponential growth.
O: Deviation from the best fit exponential growth curve.
Strengths: The deviations from the expected curves for each state are seen at or around the expected median effective date of the stay-at-home orders and these deviations are statistically significant.
Limitations: This analysis assumes that all deviations from the projected hospitalizations are a result of the stay-at-home order. Data was only available for four states.
Conclusions: Prior to enacting stay-at-home orders, each state’s cumulative COVID-19 hospitalization curve favored an exponential function over a linear function. After the median effective date for the orders, the plotted hospitalizations fell out of the 95% prediction bands for the projected exponential growth function -- suggesting that the stay-at-home orders had a significant effect on spread of COVID-19.
Chloroquine or hydroxychloroquine for COVID-19: why might they be hazardous?
JourNal: The Lancet
JourNal: The Lancet
Link
Summary
P: 96,032 COVID-19 patients from an international registry of 671 hospitals across 6 continents.
I: COVID-19 patients received chloroquine (n=1868), hydroxychloroquine (n=3016), chloroquine with a macrolide (n=3783), or hydroxychloroquine with a macrolide (n=6221) within 48 h of COVID-19 diagnosis
C: 81,144 COVID-10 patients who did not receive these drugs served as the control
O: The primary outcome for the study was in-hospital mortality and the occurrence of non-sustained or sustained ventricular tachycardia or ventricular fibrillation
Strengths: The analysis included a Cox proportional hazard model to account for many confounding variables, including age, sex, ethnicity, comorbidities, other medications across the patient population being included in the study. The large size of the population also further strengths the conclusions drawn.
Limitations: The main limitations to the study are those that are commonly inherent to any observational study such as inability to draw causation since there is no randomization along with bias and confounders when analyzing the data.
Conclusions: The results showed a significant increase in the risk of in-hospital mortality with the four treatment regimens compared with the control group. These results indicate a benefit from the absence of 4-aminoquinoline-based treatments in this population and suggest that they could even be harmful. The risk of death associated with 4-aminoquinolines alone or combined with a macrolide was similar, whereas it would be expected that the combination of two QTc-prolonging drugs would increase their proarrhythmic potential. These findings from add to preliminary reports suggesting that regimens of chloroquine or hydroxychloroquine, alone or with azithromycin, are not useful and could be harmful in hospitalized patients with COVID-19.
Summary
P: 96,032 COVID-19 patients from an international registry of 671 hospitals across 6 continents.
I: COVID-19 patients received chloroquine (n=1868), hydroxychloroquine (n=3016), chloroquine with a macrolide (n=3783), or hydroxychloroquine with a macrolide (n=6221) within 48 h of COVID-19 diagnosis
C: 81,144 COVID-10 patients who did not receive these drugs served as the control
O: The primary outcome for the study was in-hospital mortality and the occurrence of non-sustained or sustained ventricular tachycardia or ventricular fibrillation
Strengths: The analysis included a Cox proportional hazard model to account for many confounding variables, including age, sex, ethnicity, comorbidities, other medications across the patient population being included in the study. The large size of the population also further strengths the conclusions drawn.
Limitations: The main limitations to the study are those that are commonly inherent to any observational study such as inability to draw causation since there is no randomization along with bias and confounders when analyzing the data.
Conclusions: The results showed a significant increase in the risk of in-hospital mortality with the four treatment regimens compared with the control group. These results indicate a benefit from the absence of 4-aminoquinoline-based treatments in this population and suggest that they could even be harmful. The risk of death associated with 4-aminoquinolines alone or combined with a macrolide was similar, whereas it would be expected that the combination of two QTc-prolonging drugs would increase their proarrhythmic potential. These findings from add to preliminary reports suggesting that regimens of chloroquine or hydroxychloroquine, alone or with azithromycin, are not useful and could be harmful in hospitalized patients with COVID-19.
Hospitalization and Mortality among Black Patients and White Patients with Covid-19
Journal: NEJM
Journal: NEJM
Link
Summary:
P: Patients that tested positive for COVID-19
I: standard hospital treatment for COVID-19
C: White patients with Covid-19
O: Hospitalization and in-hospital death
Strengths: Large patient population (3481) with a large portion of black patients
Limitations: Study limited to a single center. Retrospective design means that care among participants was not completely standardized.
Conclusions: From the article: “In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.”
This study further confirms that Black populations have been disproportionately affected by COVID-19. While it is still not known why this is the case, data in this study indicated that Black patients arrived at the hospital with higher rates of obesity, diabetes, hypertension, and chronic kidney disease.
Summary:
P: Patients that tested positive for COVID-19
I: standard hospital treatment for COVID-19
C: White patients with Covid-19
O: Hospitalization and in-hospital death
Strengths: Large patient population (3481) with a large portion of black patients
Limitations: Study limited to a single center. Retrospective design means that care among participants was not completely standardized.
Conclusions: From the article: “In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.”
This study further confirms that Black populations have been disproportionately affected by COVID-19. While it is still not known why this is the case, data in this study indicated that Black patients arrived at the hospital with higher rates of obesity, diabetes, hypertension, and chronic kidney disease.
AIR POLLUTION: Temporary reduction in daily global CO2 emissions during the COVID-19 forced confinement
Journal: nature Climate Change
Journal: nature Climate Change
Link
Summary
P: Air quality of 69 countries, including USA and China
I: Social distancing and confinement policies’ impact on CO2 emissions in April 2020
C: CO2 emissions in April 2019
O: On April 7, 2020, global confinement decreased the daily CO2 emissions by 17%. The average of maximum daily decrease per country was 26%, but each country did not have maximum daily decreases on the same day. The largest sector that saw a decrease in CO2 emissions was surface transportation/city congestion.
Strengths: Data is publicly available, transparent about using estimated values from sector activity, methods detailed.
Limitations: The values of daily CO2 emissions were estimated changes based on sector activity. Real-time measurements using satellite is not reliable. Typically, only annual emission values are reported. Scope of pandemic is unknown, future estimates may change.
Conclusions: The decrease in April daily CO2 emissions was about 17% due to decreased energy demands from social confinement policies. Predicted values for average 2020 emission is an annual decrease of 5.7%. In the 2008 global financial crisis, a decrease of 1.4% was also observed, but in 2020 the emissions grew to 5% increase. Similarly, the IMF and others predict a rebound increase in emissions of 5.8% (global) and 3.5% (USA) in 2021. This study is meaningful because CO2 emissions have been linked to premature deaths of susceptible individuals and more understanding is needed to appropriately advise patients.
Summary
P: Air quality of 69 countries, including USA and China
I: Social distancing and confinement policies’ impact on CO2 emissions in April 2020
C: CO2 emissions in April 2019
O: On April 7, 2020, global confinement decreased the daily CO2 emissions by 17%. The average of maximum daily decrease per country was 26%, but each country did not have maximum daily decreases on the same day. The largest sector that saw a decrease in CO2 emissions was surface transportation/city congestion.
Strengths: Data is publicly available, transparent about using estimated values from sector activity, methods detailed.
Limitations: The values of daily CO2 emissions were estimated changes based on sector activity. Real-time measurements using satellite is not reliable. Typically, only annual emission values are reported. Scope of pandemic is unknown, future estimates may change.
Conclusions: The decrease in April daily CO2 emissions was about 17% due to decreased energy demands from social confinement policies. Predicted values for average 2020 emission is an annual decrease of 5.7%. In the 2008 global financial crisis, a decrease of 1.4% was also observed, but in 2020 the emissions grew to 5% increase. Similarly, the IMF and others predict a rebound increase in emissions of 5.8% (global) and 3.5% (USA) in 2021. This study is meaningful because CO2 emissions have been linked to premature deaths of susceptible individuals and more understanding is needed to appropriately advise patients.
The Remdesivir Saga Continues: Remdesivir for the Treatment of Covid-19 — Preliminary Report
Journal: NeJM
Journal: NeJM
Link
Summary:
P: The population was 1,063 randomized patients from clinical sites in the United States, Denmark, the United Kingdom, Greece, Germany, South Korea, Mexico, Spain, Japan, and Singapore.
I: Remdesivir was given via IV as a 200 mg. loading dose on day 1. Subsequently, a 100 mg. remdesivir maintenance dose was given on day 2 through 10 or “until hospital discharge or death.”
C: A matching placebo was given via IV that was equivalent in both duration and volume as the intervention drug (remdesivir).
O: Per the authors, “the primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection control purposes only.”
Strengths: Large, multi-national population used. Peer-reviewed, double-blind, randomized control trial. Demographic and medical conditions were well-balanced between the intervention and control groups.
Limitations: For patients receiving intubation or extracorpeal membrane oxygenation (ECMO) at baseline, the median recovery time could not be estimated. The authors believe this may be due to follow-up windows that were too short. The trial is ongoing; thus, this limitation may be overcome with more data.
Conclusion: Hospitalized patients with COVID-19 who were treated with remdesivir recovered quicker than those treated with placebo. In fact, patients in the remdesivir group had a median recovery time of 11 days, while those in the control group had a median recovery time of 15 days. However, patients who were already intubated or receiving ECMO at baseline did not experience the recovery benefit. This seems to suggest that remdesivir is most effective when given prior to the onset of severe lung disease. Though mortality was decreased in the remdesivir group compared to placebo, the difference is not significant. The trial is still ongoing, so perhaps additional data will reveal the effects of remdesivir on mortality. In any case, the results of the present study support remdesivir use for hospitalized COVID-19 patients to decrease recovery times.
Summary:
P: The population was 1,063 randomized patients from clinical sites in the United States, Denmark, the United Kingdom, Greece, Germany, South Korea, Mexico, Spain, Japan, and Singapore.
I: Remdesivir was given via IV as a 200 mg. loading dose on day 1. Subsequently, a 100 mg. remdesivir maintenance dose was given on day 2 through 10 or “until hospital discharge or death.”
C: A matching placebo was given via IV that was equivalent in both duration and volume as the intervention drug (remdesivir).
O: Per the authors, “the primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection control purposes only.”
Strengths: Large, multi-national population used. Peer-reviewed, double-blind, randomized control trial. Demographic and medical conditions were well-balanced between the intervention and control groups.
Limitations: For patients receiving intubation or extracorpeal membrane oxygenation (ECMO) at baseline, the median recovery time could not be estimated. The authors believe this may be due to follow-up windows that were too short. The trial is ongoing; thus, this limitation may be overcome with more data.
Conclusion: Hospitalized patients with COVID-19 who were treated with remdesivir recovered quicker than those treated with placebo. In fact, patients in the remdesivir group had a median recovery time of 11 days, while those in the control group had a median recovery time of 15 days. However, patients who were already intubated or receiving ECMO at baseline did not experience the recovery benefit. This seems to suggest that remdesivir is most effective when given prior to the onset of severe lung disease. Though mortality was decreased in the remdesivir group compared to placebo, the difference is not significant. The trial is still ongoing, so perhaps additional data will reveal the effects of remdesivir on mortality. In any case, the results of the present study support remdesivir use for hospitalized COVID-19 patients to decrease recovery times.
April 27-May 1 2020
Special population: How is immunosuppressive status affecting children and adults in SARS-CoV-2 infections? A systematic review.
Journal: J Infect
Journal: J Infect
Link
Summary:
P: immunocompromised COVID-19 patients
I: clinical outcomes (mortality, ICU admission, etc)
C: COVID-19 patients who are not immunocompromised
Limitations: of the 110 patients included, most were cancer patients (rather than an even distribution of types of conditions)
Strengths: systematic review, 16 different articles included, 110 patients
Conclusions: A systematic review yielded 16 relevant articles of 110 immunosuppressed patients (cancer, transplantation, immunodeficiency). Of these patients, 65.5% recovered or did not require intensive care, 5.5% needed intensive care or invasive ventilation, and 20.9% died. Based on their results, children and adults with immunosuppression do not seem to have a more severe disease course compared to the general population. The major risk factors for severe disease course seem to be elderly age, obesity, diabetes, cardiovascular problems, and male sex rather than immunodeficiency."
Summary:
P: immunocompromised COVID-19 patients
I: clinical outcomes (mortality, ICU admission, etc)
C: COVID-19 patients who are not immunocompromised
Limitations: of the 110 patients included, most were cancer patients (rather than an even distribution of types of conditions)
Strengths: systematic review, 16 different articles included, 110 patients
Conclusions: A systematic review yielded 16 relevant articles of 110 immunosuppressed patients (cancer, transplantation, immunodeficiency). Of these patients, 65.5% recovered or did not require intensive care, 5.5% needed intensive care or invasive ventilation, and 20.9% died. Based on their results, children and adults with immunosuppression do not seem to have a more severe disease course compared to the general population. The major risk factors for severe disease course seem to be elderly age, obesity, diabetes, cardiovascular problems, and male sex rather than immunodeficiency."
Uncommon presentations: Evaluation of ocular symptoms and tropism of SARS‐CoV‐2 in patients confirmed with COVID‐19
Journal: Acta Ophthalmol
Journal: Acta Ophthalmol
Link:
Summary:
P: Previously hospitalized, COVID-19 positive patients
I: Ocular symptoms in COVID-19
C: Pre- and post-COVID-19 ocular symptoms
Strengths: 56 lab confirmed patients, detailed ocular history obtained using both Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ)
Limitations: Reliant upon subjective recall for both pre- and post-COVID eye symptoms
Conclusion: Ocular symptoms are relatively common in COVID‐19 disease and may appear just before the onset of respiratory symptoms.
Summary:
P: Previously hospitalized, COVID-19 positive patients
I: Ocular symptoms in COVID-19
C: Pre- and post-COVID-19 ocular symptoms
Strengths: 56 lab confirmed patients, detailed ocular history obtained using both Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ)
Limitations: Reliant upon subjective recall for both pre- and post-COVID eye symptoms
Conclusion: Ocular symptoms are relatively common in COVID‐19 disease and may appear just before the onset of respiratory symptoms.
CVA and COVID-9: Large Vessel Stroke as a Presenting Feature of COVID-19 in the Young
JOurnal: NEJM
JOurnal: NEJM
Link
Summary:
P: Patients < 50 years of age with COVID-19
I: Stroke incidence in COVID-19 positive Patients
C: Typical presentation of COVID-19
Strengths: Noted comparison of incidence of younger patients with large vessel strokes in their hospital to prior admission statistics over the past 12 months to provide context. Comparison to data from Wuhan showing stroke incidence in COVID-19 positive patients. Included information on past medical history of each patient, particularly those that lead to increased stroke risk. Information on presentation, NIHSS, outcome, treatment.
Limitations: Small case series of 5 patients. Only included patients over a two-week period. Delayed presentation of patients due to reluctance to seek medical attention. Did not include information on when COVID-19 testing was obtained or risk factors for exposure in patients. Did not include information on COVID-19 respiratory symptoms or duration of symptoms.
Conclusions: Proposed that coagulopathy and vascular endothelial dysfunction may contribute to stroke incidence. Also proposed that reluctance to present to the hospital may be contributing to poor outcomes.
Summary:
P: Patients < 50 years of age with COVID-19
I: Stroke incidence in COVID-19 positive Patients
C: Typical presentation of COVID-19
Strengths: Noted comparison of incidence of younger patients with large vessel strokes in their hospital to prior admission statistics over the past 12 months to provide context. Comparison to data from Wuhan showing stroke incidence in COVID-19 positive patients. Included information on past medical history of each patient, particularly those that lead to increased stroke risk. Information on presentation, NIHSS, outcome, treatment.
Limitations: Small case series of 5 patients. Only included patients over a two-week period. Delayed presentation of patients due to reluctance to seek medical attention. Did not include information on when COVID-19 testing was obtained or risk factors for exposure in patients. Did not include information on COVID-19 respiratory symptoms or duration of symptoms.
Conclusions: Proposed that coagulopathy and vascular endothelial dysfunction may contribute to stroke incidence. Also proposed that reluctance to present to the hospital may be contributing to poor outcomes.
Remdesivir, our savior?: Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.
Journal: The Lancet
Journal: The Lancet
Link
Summary:
P: 237 patients with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia
I: IV remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions)
C: Placebo infusions for 10 days
O: Time to clinical improvement up to day 28
Strengths: Randomised, double-blind, placebo-controlled, multicentre trial. Peer Reviewed.
Limitations: Some patients were using concomitant lopinavir-rotinavir, interferons, and corticosteroids. Only included severe patients. Additionally, the study was terminated prematurely because it was difficult to enroll patients in China, where the number of Covid-19 cases was decreasing. As a result, the researchers admitted to likely insufficient power to detect assumed differences in clinical outcomes, initiation of treatment quite late in COVID-19, and the absence of data on infectious virus recovery or on possible emergence of reduced susceptibility to remdesivir.
Conclusion: The use of remdesivir did not lead to a statistically significant difference in time to clinical improvement compared to placebo. There were a similar number of adverse events between groups however treatment was stopped in 12% of the remdesivir group due to adverse events compared to 5% of the control group.
These results seem to contradict the recent publicised results fo the NIH trial which is yet to be fully released to the public. What we know about this trial so far:
P: Hospitalized patients with advanced COVID-19 and lung involvement
I: 11 days of Remdesivir
C: 15 days of placebo.
Strengths: a randomized, controlled trial involving 1063 patients, A total of 68 sites ultimately joined the study—47 in the United States and 21 in countries in Europe and Asia.
Limitations: The preliminary results from this trial were drawn from an independent data and safety monitoring board (DSMB). The study still needs to be properly peer-reviewed.
Conclusions: Preliminary results indicate that patients who received remdesivir had a 31% faster time to recovery than those who received placebo (p<0.001). Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo. Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059), HOWEVER, these results were not statistically significant.
It begs the questions, as the results of RCTs of Remdesivir continue to be released, will a pooled meta-analysis demonstrate it to be a "game changer" or a therapy that adds costs with little clinical value?
Summary:
P: 237 patients with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia
I: IV remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions)
C: Placebo infusions for 10 days
O: Time to clinical improvement up to day 28
Strengths: Randomised, double-blind, placebo-controlled, multicentre trial. Peer Reviewed.
Limitations: Some patients were using concomitant lopinavir-rotinavir, interferons, and corticosteroids. Only included severe patients. Additionally, the study was terminated prematurely because it was difficult to enroll patients in China, where the number of Covid-19 cases was decreasing. As a result, the researchers admitted to likely insufficient power to detect assumed differences in clinical outcomes, initiation of treatment quite late in COVID-19, and the absence of data on infectious virus recovery or on possible emergence of reduced susceptibility to remdesivir.
Conclusion: The use of remdesivir did not lead to a statistically significant difference in time to clinical improvement compared to placebo. There were a similar number of adverse events between groups however treatment was stopped in 12% of the remdesivir group due to adverse events compared to 5% of the control group.
These results seem to contradict the recent publicised results fo the NIH trial which is yet to be fully released to the public. What we know about this trial so far:
P: Hospitalized patients with advanced COVID-19 and lung involvement
I: 11 days of Remdesivir
C: 15 days of placebo.
Strengths: a randomized, controlled trial involving 1063 patients, A total of 68 sites ultimately joined the study—47 in the United States and 21 in countries in Europe and Asia.
Limitations: The preliminary results from this trial were drawn from an independent data and safety monitoring board (DSMB). The study still needs to be properly peer-reviewed.
Conclusions: Preliminary results indicate that patients who received remdesivir had a 31% faster time to recovery than those who received placebo (p<0.001). Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo. Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059), HOWEVER, these results were not statistically significant.
It begs the questions, as the results of RCTs of Remdesivir continue to be released, will a pooled meta-analysis demonstrate it to be a "game changer" or a therapy that adds costs with little clinical value?
NeuroScience: Is the Collapse of the Respiratory Center in the Brain Responsible for Respiratory Breakdown in COVID-19 Patients?
JOurnal: ACS Chem NeuroScience
JOurnal: ACS Chem NeuroScience
Viewpoint article that addresses the growing evidence of neurological sequelae of SARS-CoV2 including anosmia, dysgeusia, etc. Specifically concerning is the devastating respiratory effects of the virus and how the central nervous system could be involved. The article specifically discusses the growing hypothesis that the virus may gain access to the brain via the olfactory bulb and from there target areas such as the thalamus and brainstem by trans-synaptic transfer. This theory seems to correlate well with case series in China which have shown neurologic symptoms as prevalent in COVID-19 patients and were very common in patients with severe infection according to their respiratory status.
So far the brain has not neen considered one of the primary organs affected by the virus, but given the growing data, it will be helpful to really study in depth the link between these CNS deficits, especially anosmia, and how it correlates with severity of respiratory disease as it may alter the approach of triage and treatment earlier in the disease course.
So far the brain has not neen considered one of the primary organs affected by the virus, but given the growing data, it will be helpful to really study in depth the link between these CNS deficits, especially anosmia, and how it correlates with severity of respiratory disease as it may alter the approach of triage and treatment earlier in the disease course.
April 18-24 2020
Testing concerns: Detection and analysis of nucleic acid in various biological samples of COVID-19 patients
Journal:: Travel Med Infect Dis
Journal:: Travel Med Infect Dis
Link
Summary::
P: confirmed COVID-19 patients
I: nasopharyngeal swab
C: other sample types (sputum, blood, feces, anal swabs)
O: positive test result of real-time fluorescence RT-PCR 2019-nCov NAT
Limitations: Chinese population; only 132 patients; only 1 medical center; the test used to confirm COVID-19 status was also one of the tests being compared in the study (nasopharyngeal swab)
Strengths: All tests were run in the same lab with the same testing kit, technician, and controls
Conclusions: These authors wanted to know which sample was the most reliable in terms of least false negatives. They took 132 patients that were confirmed positive via nasopharyngeal swab, and pulled multiple nasopharyngeal, sputum, blood, fecal, and anal samples. The positive rate of each sample’s 2019-nCov NAT were: nasopharyngeal 38.13%, sputum 48.68%, blood 3.03%, feces 9.83%, anal 10.00%. Based on this, they concluded that nasopharyngeal testing alone is not sufficient, and that the best testing seems to be from sputum. Evaluation of the data is concerning as there seems to be a high risk of false negatives that may prompt discharge and also explain why there have been reported cases of subsequent positive that may not necessarily mean reinfection. This paper poses the question of whether other sample site such as blood or digestive tract (fecal/anal swab) should be included in the discharge criteria. Given the short comings of our current tests, this link will also direct you to an older publication from February in which researchers came up with a point‐of‐care lateral flow immunoassay (LFIA) test product which detected IgM and IgG with a sensitivity of 88.66% and a specificity of 90.63%. Although contigent on a number of factors such as unknown limits of detection and variation in immune response between patients, there were some notable advantages when compated to RT‐PCR tests, including minimal need for equipment, ease of use and training allowing it to be used in a large number of settings.
Summary::
P: confirmed COVID-19 patients
I: nasopharyngeal swab
C: other sample types (sputum, blood, feces, anal swabs)
O: positive test result of real-time fluorescence RT-PCR 2019-nCov NAT
Limitations: Chinese population; only 132 patients; only 1 medical center; the test used to confirm COVID-19 status was also one of the tests being compared in the study (nasopharyngeal swab)
Strengths: All tests were run in the same lab with the same testing kit, technician, and controls
Conclusions: These authors wanted to know which sample was the most reliable in terms of least false negatives. They took 132 patients that were confirmed positive via nasopharyngeal swab, and pulled multiple nasopharyngeal, sputum, blood, fecal, and anal samples. The positive rate of each sample’s 2019-nCov NAT were: nasopharyngeal 38.13%, sputum 48.68%, blood 3.03%, feces 9.83%, anal 10.00%. Based on this, they concluded that nasopharyngeal testing alone is not sufficient, and that the best testing seems to be from sputum. Evaluation of the data is concerning as there seems to be a high risk of false negatives that may prompt discharge and also explain why there have been reported cases of subsequent positive that may not necessarily mean reinfection. This paper poses the question of whether other sample site such as blood or digestive tract (fecal/anal swab) should be included in the discharge criteria. Given the short comings of our current tests, this link will also direct you to an older publication from February in which researchers came up with a point‐of‐care lateral flow immunoassay (LFIA) test product which detected IgM and IgG with a sensitivity of 88.66% and a specificity of 90.63%. Although contigent on a number of factors such as unknown limits of detection and variation in immune response between patients, there were some notable advantages when compated to RT‐PCR tests, including minimal need for equipment, ease of use and training allowing it to be used in a large number of settings.
Fecal Viral shedding: Diarrhea is associated with prolonged symptoms and viral carriage in COVID-19
Journal: Clin Gastroenterol Hepatol.
Journal: Clin Gastroenterol Hepatol.
Link
Summary:
P: Diarrhea as an associated symptom of COVID-19
I: COVID-19 patients with diarrhea and viral carriage
C: COVID-19 patients with no diarrhea and corresponding viral carriage
Limitations: Case series. Relatively small number of cases, n=84. All patients were healthcare workers. No long term follow up, cases were followed for the duration of hospitalization during the time period of January 7th to February 19th.
Strengths: Comparison of viral carriage between COVID-19 patients with respiratory symptoms with vs. without diarrhea. Clear criteria for confirmation of diagnosis, monitored parameters, and tracking of viral RNA via stool RT-PCR testing.
Conclusions: 31% of the 84 patients studied had diarrhea and had longer duration of fever and dyspnea which was statistically significant from those without (p<0.05). Stool samples tested positive for RNA in 69% of those with diarrhea vs. 17% in those without. Those with diarrhea had lower proportion of testing negative by throat swab compared to those without during hospitalization. Demonstrated that elimination of viral RNA from stool took longer than elimination for the nose or throat. These results may have other interesting implications apart from further elucidating disease course, but also when developing new guidlines to minimize disease spread. In this interesting opinion piece, researchers pose the question that given the findings of viral shedding in stool whether exposure to bio-aerosols from toilets in hospitals can put healthcare workers, hospitalized patients, and environmental services staff at higher risk of severe or critical disease?
Summary:
P: Diarrhea as an associated symptom of COVID-19
I: COVID-19 patients with diarrhea and viral carriage
C: COVID-19 patients with no diarrhea and corresponding viral carriage
Limitations: Case series. Relatively small number of cases, n=84. All patients were healthcare workers. No long term follow up, cases were followed for the duration of hospitalization during the time period of January 7th to February 19th.
Strengths: Comparison of viral carriage between COVID-19 patients with respiratory symptoms with vs. without diarrhea. Clear criteria for confirmation of diagnosis, monitored parameters, and tracking of viral RNA via stool RT-PCR testing.
Conclusions: 31% of the 84 patients studied had diarrhea and had longer duration of fever and dyspnea which was statistically significant from those without (p<0.05). Stool samples tested positive for RNA in 69% of those with diarrhea vs. 17% in those without. Those with diarrhea had lower proportion of testing negative by throat swab compared to those without during hospitalization. Demonstrated that elimination of viral RNA from stool took longer than elimination for the nose or throat. These results may have other interesting implications apart from further elucidating disease course, but also when developing new guidlines to minimize disease spread. In this interesting opinion piece, researchers pose the question that given the findings of viral shedding in stool whether exposure to bio-aerosols from toilets in hospitals can put healthcare workers, hospitalized patients, and environmental services staff at higher risk of severe or critical disease?
Other DIagnostics: Laboratory data analysis of novel coronavirus (COVID-19) screening in 2510 patients
Journal: CLINICA CHIMICA ACTA
Journal: CLINICA CHIMICA ACTA
Link
Summary:
P: screened patients for COVID-19
I: NAT and hematology data
C: Influenza A and B vs COVID-19 vs negative patients
Limitations: Screening data from only 1 hospital in China; although 2510 patients screened, only 32 were positive for COVID-19, only 57 were positive for Influenza A, and only 84 were positive for Influenza B
Strengths: 2510 patients total included; the same lab with the same testing kits were used to determine both COVID-19 and Influenza positivity; many hematologic indices were included, including cell counts, differentials, and many biochemical indicators
Conclusions: Of the 2510 patients screened, 32 (1.3%) were COVID-19 positive via pharyngeal swab (with 8 of those also having positive fecal samples), 57 (2.3%) were Influenza A positive, and 84 (3.3%) were Influenza B positive. Therefore, Influenza was more prevalent than COVID-19. When comparing hematology indices fo COVID-19 patients to negative patients, HFLC%, MPV, MONO%, TP, and ALB were increased, whereas PLT-I, WBC, LYMPH#, BASO%, BASO#, EO%, EO#, PLT, PCT, IG%, NEOT#, urea, and IP were decreased. Compared to patients infected with influenza A/B, MPV, PDW, TP, ALB, ALT, CO2CP were increased, whereas EO%, EO#, IP, and CK-MB were reduced. Therefore, hematologic indices can be used to differentiate between these two infections.
Summary:
P: screened patients for COVID-19
I: NAT and hematology data
C: Influenza A and B vs COVID-19 vs negative patients
Limitations: Screening data from only 1 hospital in China; although 2510 patients screened, only 32 were positive for COVID-19, only 57 were positive for Influenza A, and only 84 were positive for Influenza B
Strengths: 2510 patients total included; the same lab with the same testing kits were used to determine both COVID-19 and Influenza positivity; many hematologic indices were included, including cell counts, differentials, and many biochemical indicators
Conclusions: Of the 2510 patients screened, 32 (1.3%) were COVID-19 positive via pharyngeal swab (with 8 of those also having positive fecal samples), 57 (2.3%) were Influenza A positive, and 84 (3.3%) were Influenza B positive. Therefore, Influenza was more prevalent than COVID-19. When comparing hematology indices fo COVID-19 patients to negative patients, HFLC%, MPV, MONO%, TP, and ALB were increased, whereas PLT-I, WBC, LYMPH#, BASO%, BASO#, EO%, EO#, PLT, PCT, IG%, NEOT#, urea, and IP were decreased. Compared to patients infected with influenza A/B, MPV, PDW, TP, ALB, ALT, CO2CP were increased, whereas EO%, EO#, IP, and CK-MB were reduced. Therefore, hematologic indices can be used to differentiate between these two infections.
Practice Recs: Emergency tracheal intubation in 202 patients with COVID-19 in Wuhan, China: lessons learnt and international expert recommendations
Journal: Br J Anaesth
Journal: Br J Anaesth
Link
Summary:
P: COVID-19 patients
I: emergency intubation
C: case series from 2 different hospitals
O: results and consequences of intubation
Limitations: Chinese population only; only 202 patients
Strengths: multiple centers included; retrospective
Conclusions: The authors wished to determine recommendations for tracheal intubation in COVID-19 patients. Their results from compiling the data from the 2 hospitals in the retrospective study include: Among the COVID-19 patients requiring urgent intubation, the majority were males (67.3%) and older (63.4% > 65 yo). Hypoxaemia was predominant (75.2%) and hypotension was common (17.8% during and 22.3% afterwards). A technique based on RSI and videolaryngoscopy enabled prompt tracheal intubation and was universally successful. Cardiac arrest
occurred in 2%, and pneumothorax and early mortality were both observed (5.9% and 10.4% respectfully). Despite differing approaches to PPE, there was no intubation-related healthcare worker COVID-19 infection up to 14 days post-procedure. The authors also included a flow chart of tracheal intubation strategy based on their collected data
Summary:
P: COVID-19 patients
I: emergency intubation
C: case series from 2 different hospitals
O: results and consequences of intubation
Limitations: Chinese population only; only 202 patients
Strengths: multiple centers included; retrospective
Conclusions: The authors wished to determine recommendations for tracheal intubation in COVID-19 patients. Their results from compiling the data from the 2 hospitals in the retrospective study include: Among the COVID-19 patients requiring urgent intubation, the majority were males (67.3%) and older (63.4% > 65 yo). Hypoxaemia was predominant (75.2%) and hypotension was common (17.8% during and 22.3% afterwards). A technique based on RSI and videolaryngoscopy enabled prompt tracheal intubation and was universally successful. Cardiac arrest
occurred in 2%, and pneumothorax and early mortality were both observed (5.9% and 10.4% respectfully). Despite differing approaches to PPE, there was no intubation-related healthcare worker COVID-19 infection up to 14 days post-procedure. The authors also included a flow chart of tracheal intubation strategy based on their collected data
THerapeutics: An exploratory randomized controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19 (ELACOI). *Disclaimer! not yet peer reviewed*
Link
Summary:
P: 86 patients with mild/moderate COVID-19
I: Lopinavir/ritonavir or arbidol monotherapy
C: No antiviral medication
O: Average time of positive-to-negative conversion of SARS-CoV-2 nucleic acid and conversion rates at days 7 and 14.
Strengths: Randomized control trial (2:2:1)
Limitations: Small sample size. Study did not include patients with severe or critical disease or patients with many comorbidities. Study was conducted at only one center.
Conclusion: Lopinavir/ritonavir and arbidol did not shorten the time of positive-to-negative conversion of COVID-19, nor did they improve the symptoms of COVID-19 or pneumonia on lung CT imaging at 7 days and 14 days. Moreover, more patients treated with LPV/r progressed from mild/moderate to severe/critical status than patients from the other two groups. This data is consistent with previous retrospective and clinical data that lopinavir/ritonavir and arbidol have not been effective in treating COVID-19.
Summary:
P: 86 patients with mild/moderate COVID-19
I: Lopinavir/ritonavir or arbidol monotherapy
C: No antiviral medication
O: Average time of positive-to-negative conversion of SARS-CoV-2 nucleic acid and conversion rates at days 7 and 14.
Strengths: Randomized control trial (2:2:1)
Limitations: Small sample size. Study did not include patients with severe or critical disease or patients with many comorbidities. Study was conducted at only one center.
Conclusion: Lopinavir/ritonavir and arbidol did not shorten the time of positive-to-negative conversion of COVID-19, nor did they improve the symptoms of COVID-19 or pneumonia on lung CT imaging at 7 days and 14 days. Moreover, more patients treated with LPV/r progressed from mild/moderate to severe/critical status than patients from the other two groups. This data is consistent with previous retrospective and clinical data that lopinavir/ritonavir and arbidol have not been effective in treating COVID-19.
BOnus short read: UPSURGE OF DEEP VENOUS THROMBOSIS IN PATIENTS AFFECTED BY COVID-19: PRELIMINARY DATA AND POSSIBLE EXPLANATIONS
Journal: Journal of Vascular Surgery: Venous and Lymphatic Disorders
Journal: Journal of Vascular Surgery: Venous and Lymphatic Disorders
Link
Summary:
During the last month, the authors have noticed a remarkable increase in the diagnosis of DVT at their Italian medical center among patients infected by coronavirus disease 2019. They cite the most frequent localization at the iliac-femoral-popliteal axis, followed by the brachial-axillary veins and the calf veins. They discuss possible mechanisms, including the previously studied link between DVT and ARDS in influenza A H1N1, as well as known increase in procoagulant factors, such as D-dimer and tissue factor, in other community-acquired pneumonias. Lastly they discuss possible contribution of CPAP as a component, especially in patients with involvement of the upper limbs. Given the increase in cases of PE and DVT noted in the US as well, this paper asserts the need to gather formal data to establish the incidence, mortality rate, and the opportunity of a screening program and prophylactic therapy in these patients.
Summary:
During the last month, the authors have noticed a remarkable increase in the diagnosis of DVT at their Italian medical center among patients infected by coronavirus disease 2019. They cite the most frequent localization at the iliac-femoral-popliteal axis, followed by the brachial-axillary veins and the calf veins. They discuss possible mechanisms, including the previously studied link between DVT and ARDS in influenza A H1N1, as well as known increase in procoagulant factors, such as D-dimer and tissue factor, in other community-acquired pneumonias. Lastly they discuss possible contribution of CPAP as a component, especially in patients with involvement of the upper limbs. Given the increase in cases of PE and DVT noted in the US as well, this paper asserts the need to gather formal data to establish the incidence, mortality rate, and the opportunity of a screening program and prophylactic therapy in these patients.
April 13-17 2020
Interesting Implications: COVID-19, Arrhythmic Risk and Inflammation: Mind the Gap!
Journal: Circulation
Journal: Circulation
Link
Summary:
P: Covid-19 patients with cardiac arrythmias
I: Evaluating unique pro-arrythmic role of high-grade systemic inflammatory state characteristic of COVID-19 (Specifically using CRP and IL-6 as markers)
C: Current belief is that myocardial damage causes enhanced arrhythmic risk. However, evidence in ICU patients, despite the high frequency of arrhythmias (~50% of cases), only a half showed acute cardiac injury.
Limitations: Opinion article reviewing past studies assessing role of inflammation in arrythmias, not COVID-19 specific.
Strengths: Provides basic science explanation for clinical observations that may influence treatment.
Conclusion: Suggests that factors other than myocardial damage are also involved in enhancing the arrhythmic risk in COVID-19. Food for thought that physicians should always consider COVID patients as those at increased arrhythmic risk. The extent of systemic inflammation, as reflected by circulating CRP (and IL-6) levels, should be considered to assess the benefit/risk ratio when considering use fo QT-prolonging medications. Additionally, provides merit to further investigation of the use of anti-IL-6 targeted therapies (tocilizumab,sarilumab) to COVID-19 patients as a way of reducing high arrhythmic risk.
Summary:
P: Covid-19 patients with cardiac arrythmias
I: Evaluating unique pro-arrythmic role of high-grade systemic inflammatory state characteristic of COVID-19 (Specifically using CRP and IL-6 as markers)
C: Current belief is that myocardial damage causes enhanced arrhythmic risk. However, evidence in ICU patients, despite the high frequency of arrhythmias (~50% of cases), only a half showed acute cardiac injury.
Limitations: Opinion article reviewing past studies assessing role of inflammation in arrythmias, not COVID-19 specific.
Strengths: Provides basic science explanation for clinical observations that may influence treatment.
Conclusion: Suggests that factors other than myocardial damage are also involved in enhancing the arrhythmic risk in COVID-19. Food for thought that physicians should always consider COVID patients as those at increased arrhythmic risk. The extent of systemic inflammation, as reflected by circulating CRP (and IL-6) levels, should be considered to assess the benefit/risk ratio when considering use fo QT-prolonging medications. Additionally, provides merit to further investigation of the use of anti-IL-6 targeted therapies (tocilizumab,sarilumab) to COVID-19 patients as a way of reducing high arrhythmic risk.
Case Report: Abdominal and testicular pain: An atypical presentation of COVID-19
Journal: Am J Emerg Med.
Journal: Am J Emerg Med.
Link
Summary:
P: Patients with SARS-CoV-2
I: Atypical presentation of SARS-CoV-2 patients
C: Typical presentation of SARS-CoV-2 patients
Limitations: Single case report. Details were provided on work up as well as the patient’s potential exposure.
Strengths: Inclusion of basic data on prevalence of atypical presentations and discussion of possible benefits of widespread PPE use for all patient interactions.
Conclusions: Case report of a 41-year-old who presented to the ED with abdominal, testicular, and back pain in addition to subjective fevers. No abnormal findings were found on chest x-ray. No respiratory complaints. Ground glass opacification revealed on CT at the lung bases. Found several days later to have tested positive for COVID-19. No PPE was worn during the duration of his ED visit. Authors concluded that PPE should be worn at all times as community spread increases.
Summary:
P: Patients with SARS-CoV-2
I: Atypical presentation of SARS-CoV-2 patients
C: Typical presentation of SARS-CoV-2 patients
Limitations: Single case report. Details were provided on work up as well as the patient’s potential exposure.
Strengths: Inclusion of basic data on prevalence of atypical presentations and discussion of possible benefits of widespread PPE use for all patient interactions.
Conclusions: Case report of a 41-year-old who presented to the ED with abdominal, testicular, and back pain in addition to subjective fevers. No abnormal findings were found on chest x-ray. No respiratory complaints. Ground glass opacification revealed on CT at the lung bases. Found several days later to have tested positive for COVID-19. No PPE was worn during the duration of his ED visit. Authors concluded that PPE should be worn at all times as community spread increases.
Special population: Outcome of Coronavirus spectrum infections (SARS,MERS, COVID 1 -19) during pregnancy: a systematic review and meta-analysis. Journal: American Journal ofObstetrics & Gynecology MFM
Link
Summary:
P: pregnant women with a confirmed Coronavirus related illness, defined as either SARS, MERS or COVID-19.
C: General population of pregnant women
Strengths: Meta-analysis. First systematic review exploring pregnancy and perinatal outcomes of coronavirus infections occurring during pregnancy.
Limitations: Majority of data from studies with small sample sizes and case reports
Conclusion: In pregnant women with coronavirus infections, including COVID-19, pre-term birth is most common, followed by miscarriage, preeclampsia, cesarean, and perinatal death. Although there have been numerous reports of neonatal infection, there are no confirmed cases of vertical transmission.
Summary:
P: pregnant women with a confirmed Coronavirus related illness, defined as either SARS, MERS or COVID-19.
C: General population of pregnant women
Strengths: Meta-analysis. First systematic review exploring pregnancy and perinatal outcomes of coronavirus infections occurring during pregnancy.
Limitations: Majority of data from studies with small sample sizes and case reports
Conclusion: In pregnant women with coronavirus infections, including COVID-19, pre-term birth is most common, followed by miscarriage, preeclampsia, cesarean, and perinatal death. Although there have been numerous reports of neonatal infection, there are no confirmed cases of vertical transmission.
Diagnostics: "COVID-19 pneumonia manifestations at the admission on chest ultrasound, radiographs, and CT: single-center study and comprehensive radiologic literature review”
Journal: Eur J Radiol .
Journal: Eur J Radiol .
Link
Summary:
P: lab-confirmed SARS-CoV-2 patients hospitalized in Valduce Hospital (Italy)
I: imaging studies (US, CXR, CT)
C: other publications of COVID-19 patient imaging
Limitations: Single-center study; Small sample size of only 58 patients, not all having all imaging studies done; No comparison to non-COVID-19 patients to determine specificity; No follow-up
Strengths: Retrospective study of consecutive patients; Wide age range of adults
Conclusions: These authors attempted to provide an informative picture for radiologists to assist in a faster and sooner identification of COVID-19 pneumonia. Relevant for instances of high clinical suspicion but delayed laboratory test results.
Summary:
P: lab-confirmed SARS-CoV-2 patients hospitalized in Valduce Hospital (Italy)
I: imaging studies (US, CXR, CT)
C: other publications of COVID-19 patient imaging
Limitations: Single-center study; Small sample size of only 58 patients, not all having all imaging studies done; No comparison to non-COVID-19 patients to determine specificity; No follow-up
Strengths: Retrospective study of consecutive patients; Wide age range of adults
Conclusions: These authors attempted to provide an informative picture for radiologists to assist in a faster and sooner identification of COVID-19 pneumonia. Relevant for instances of high clinical suspicion but delayed laboratory test results.
Bonus Therapeutics: COVID-19: A Brief Overview of the Discovery Clinical Trial
Journal: Pharmaceuticals
Journal: Pharmaceuticals
Link
A brief communication paper that focuses on the four treatments recommended by WHO and included in the first clinical trial of the European Discovery project. This study initiated on March 22, 2020 and will enroll 3100 patients.
Goal: determine the most effective specific drug to cure patients infected by SARS-CoV-2.
This article also details reasoning behind drug choices and recommended dosing/treatment regimens for each drug.
A brief communication paper that focuses on the four treatments recommended by WHO and included in the first clinical trial of the European Discovery project. This study initiated on March 22, 2020 and will enroll 3100 patients.
Goal: determine the most effective specific drug to cure patients infected by SARS-CoV-2.
This article also details reasoning behind drug choices and recommended dosing/treatment regimens for each drug.
Disclaimer: The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for informational purposes only.
If you have any questions, please reach out to Krishna Shah (krshah@augusta.edu) or Elena Diller (ediller@augusta.edu).
If you have any questions, please reach out to Krishna Shah (krshah@augusta.edu) or Elena Diller (ediller@augusta.edu).