- Last Updated: May 31, 2023 10:55 AM
- URL: https://guides.himmelfarb.gwu.edu/SituationReport
Key updates in treatment for COVID-19:
Key updates in treatment for COVID-19:
Title: Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review & meta-analysis
Publisher: Canadian Medical Assn Journal
Publication Date: May 22, 2020
URL: https://www.cmaj.ca/content/early/2020/05/22/cmaj.200642.long
Key Takeaway: In this is a meta-analysis of studies on the use of convalescent plasma in treatment for several severe respiratory infections – mostly influenza – and concludes that in non-COVID-19 severe respiratory viral infections there is indirect, very low-quality evidence that raises the possibility that convalescent plasma has minimal or no benefit in the treatment of COVID-19 and low-quality evidence that it does not cause serious adverse events. The authors assert that the merit of convalescent plasma is its apparent low rate of serious adverse effects and although this may be an advantage over other unproven therapies for COVID-19, it is insufficient to justify its use without associated evidence of efficacy.
Title: Impact of anticoagulation prior to COVID-19 infection: a propensity score- matched cohort study
Publisher: Blood
Publication Date:
URL:
https://ashpublications.org/blood/article/doi/10.1182/blood.2020006941/458074/Impact-of- anticoagulation-prior-to-COVID19
Key Takeaway: This report fromNew York is a retrospective analysis of 3,772 patients with confirmed COVID-19, comparing outcomes among those who were and were not receiving anticoagulation for unrelated indications at the time of COVID-19 diagnosis. There was no statistically significant difference in survival (p= 0.367) and time to mechanical ventilation (p=0.742) between the two groups.
Title: Remdesivir for 5 or 10 Days in Patients with Severe Covid-19
Publisher: NEJM
Publication Date: May 27, 2020
URL: https://www.nejm.org/doi/full/10.1056/NEJMoa2015301?url_ver=Z39.88- 2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Key Takeaway: This is an open label phase 3 RCT of 397 patients with severe Covid-19 NOT requiring mechanical ventilation with no placebo control to assess the impact of a 5 or 10-day course of remdesivir looking at an endpoint of clinical status assessed on a 7-point ordinal scale. Results: “In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir.
Title: Remdesivir for the Treatment of Covid-19 — Preliminary Report
Publisher: NEJM
Publication Date: May 22, 2020
URL: https://www.nejm.org/doi/full/10.1056/NEJMoa2007764?query=featured_home
Key Takeaway: This is the published data from a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients received either remdesivir or placebo for up to 10 days. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) show that those who received remdesivir had a median recovery time of 11 days, as compared with 15 days in those who received placebo with the estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for a high percentage of both groups.
The authors conclude that the findings support the use of remdesivir for patients who are hospitalized with Covid-19 and require supplemental oxygen therapy. But, given high mortality despite the use of remdesivir, “it is clear that treatment with an antiviral drug alone is not likely to be sufficient. Future strategies should evaluate antiviral agents in combination with other therapeutic approaches or combinations of antiviral agents to continue to improve patient outcomes in Covid-19.”
Title: Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: A rapid review
Publisher: Cochrane Database of Systematic Reviews
Publication Date: May 14, 2020
URL: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013600/full
Key Takeaway: Review of 8 available studies on convalescent plasma. Six reported on clinical outcomes and all 6 showed improvement as measured by need for respiratory support. However, all 8 studies were poor quality (not randomized, no controls) and their results could be related to the natural progression of the disease, other treatments that the participants received, or to convalescent plasma. Highlights need for further investigation: 48 ongoing studies: 47 evaluating convalescent plasma and 1 evaluating hyperimmune immunoglobulin, of which 22 are randomized.
Title: Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
Publisher: Nature
Publication Date: May 18, 2020
URL: https://www-nature-com.proxygw.wrlc.org/articles/s41586-020-2349-y#article-info
Key Takeaway: Important for potential for vaccine development, multiple monoclonal antibodies targeting SARS-CoV-2 spike gylcoprotein were identified from memory B cells of an individual who was infected with SARS-CoV in 2003. Using cryo-electron microscopy and binding assays, one antibody, named S309, was found to potently neutralize SARS-CoV-2 by engaging the S receptor-binding domain.
Title: Myth Busters: Dietary Supplements and COVID-19.
Publisher: Annals of Pharmacotherapy
Publication Date: May 12, 2020
URL: https://journals.sagepub.com/doi/pdf/10.1177/1060028020928052
Key Takeaway: This article reviews theoretical mechanisms and evidence related to efficacy and safety of select supplements in the setting of COVID-19, including vitamin C, vitamin D, zinc, elderberry, and silver. Evidence evaluating these supplements in COVID-19 patients is lacking, and providers and patients should not rely on dietary supplements to prevent or treat COVID-19.
Title: Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study
Publisher: Lancet Rheumatology
Publication Date: May 7, 2020
URL: https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30127-2/fulltext
Key Takeaway: Retrospective cohort study from Italy comparing 29 patients with ARDS on CPAP treated with high dose IV anakinra in addition to standard treatment showed significantly greater survival at 21 days (90% versus 56%, p=0.009) compared to 16 patients with ARDS on CPAP on standard treatment. Invasive mechanical ventilation-free survival was higher in the anakinra group versus standard treatment group though not statistically significant (72% versus 50%, p=0.15). Rates of bacteremia were comparable between the groups. Discontinuation of anakinra in setting of adverse effects was not followed by inflammatory relapses. These are interesting findings, but being a small retrospective cohort study, RCTs are needed to further evaluate this potential threapy.
Title: Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial
Publisher: The Lancet
Publication Date: May 8, 2020
URL: https://doi.org/10.1016/S0140-6736(20)31042-4
Key Takeaway: Early triple antiviral therapy (n=86) was safe and superior to lopinavir–ritonavir alone (n=41) in alleviating symptoms and shortening the duration of viral shedding (median 7 days versus 12 days from initiation to negative nasopharyngeal swab) and hospital stay in patients with mild to moderate COVID-19. Adverse events limited to nausea, diarrhea, fever, and one case of biochemical hepatitis in control group, without difference between the groups.
Title: Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State.
Publisher: JAMA. Published online
Publication Date: May 11, 2020
URL: https://jamanetwork.com/journals/jama/fullarticle/2766117
Key Takeaway: Large NY retrospective cohort study found no difference in mortality in hospitalized COVID-19 patients treated with hydroxychloroquine (n=271), azithromycin (n=211), or both (n=735) compared to patients who received neither (n=221). Compared with patients receiving neither, patients receiving both were significantly more likely to experience cardiac arrest (adjusted OR, 2.13 [95% CI, 1.12-4.05]), though the combination group was sicker at baseline. No differences in relative likelihood of abnormal EKG findings.
Note: This study, along with other previous studies regarding hydroxychloroquine and the FDA warning on its use, suggests there is no compelling evidence to continue use of these drugs for COVID-19 infection except in the context of an approved clinical trial.
Title: Rapid Implementation of a COVID-19 Remote Patient Monitoring Program
Publisher: Journal of the American Medical Information Association
Publication Date: May 11, 2020
URL: https://doi.org/10.1093/jamia/ocaa097
Key Takeaway: 2255 suspected/confirmed COVID-19 patients in a Minnesota health system used a remote patient monitoring tool (GetWellLoop), allowing two-way communication between patients and healthcare team (comprised of medical students, residents, supervising physicians and nurse practitioners), via text messaging platform and phone calls. Program was staffed 24/7. 74% of 300 enrolled patients surveyed would be extremely likely to recommend their doctor.
Title: A strategic approach to COVID-19 vaccine R&D.
Publisher: Science
Publication Date: May 11, 2020
URL: https://science.sciencemag.org/content/early/2020/05/08/science.abc5312
Key Takeaway: An article outlining the challenges with vaccine development, relevant clinical and immunologic endpoints that need to be targeted, available vaccine platforms and current status of progress, how the public and private sector need to collaborate to speed up development, and funding needs to scale up vaccine manufacture.
Title: Observational Study of Hydroxychloroquine in Hospitalized Patients with COVID-19
Publisher: New England Journal of Medicine
Publication Date: May 8 2020
URL: https://www.nejm.org/doi/full/10.1056/NEJMoa2012410
Key Takeaways: In an observational study, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death.
Title: Association of Treatment Dose Anticoagulation with In-Hospital Survival Among Hospitalized Patients with COVID-19
Publisher: Journal of the American College of Cardiology
Publication Date: May 2020
URL: http://www.onlinejacc.org/content/early/2020/05/05/j.jacc.2020.05.001
Key Takeaways: A case series of 2773 COVID patients at five NYC hospitals were studied to determine if anticoagulation therapy affected survival. The mortality rate of ICU patients receiving anticoagulation was 29% compared to 63% in those not anticoagulated. Of those who died, anticoagulated patients survived significantly longer.
Title: How to Prescribe Controlled Substances to Patients During the COVID-19 Public Health Emergency
Publisher: US Drug Enforcement Administration
Publication Date: algorithm May 5 2020; guidelines March 31, 2020
URL: https://nabp.pharmacy/wp-content/uploads/2020/04/DEA-DC-023DEA075Decision_Tree_Final_33120_2007.pdf
See also: https://www.deadiversion.usdoj.gov/coronavirus.html
Key Takeaways: The Drug Enforcement Administration (DEA) has adopted policies to allow DEA-registered practitioners to prescribe controlled substances without having to interact in-person with their patients.
Title: Effectiveness of convalescent plasma therapy in severe COVID-19 patients
Publisher: Proceedings of the National Academy of Sciences of the USA
Publication Date: 28 April 2020
URL: https://www.pnas.org/content/117/17/9490
Key Takeaways: The results from 10 severe adult cases showed that one dose of convalescent plasma was well tolerated and could significantly increase or maintain the neutralizing antibodies at a high level. Clinical symptoms and paraclinical criteria rapidly improved, and radiological examination showed varying degrees of absorption of lung lesions. These results indicate that CP can serve as a promising rescue option for severe COVID-19, while a randomized trial is warranted.
Title: Recommendations from the CSO-HNS taskforce on performance of tracheotomy during the COVID-19 pandemic
Publisher: Journal of Otolaryngology - Head & Neck Surgery
Publication Date: 27 April 2020
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184547/
doi: 10.1186/s40463-020-00414-9
Key Takeaways: Report stated that extended endotracheal intubation should be the standard of care for the entire duration of ventilation in the vast majority of patients. Pre-operative COVID-19 testing is highly recommended for any non-emergent procedure.
Title: Recent progress and challenges in drug development against COVID
Publisher: Elsevier - Infection, Genetics and Evolution,
Publication Date: April 19, 2020
URL: https://www.sciencedirect.com/science/article/pii/S1567134820301581
Key Takeaway: Review summarizes the existing state of knowledge about COVID-19, available medications, and treatment options.
Diagnostics
Title: Olfactory and gustatory dysfunctions as a clinical presentation of mild‐to‐moderate forms of the coronavirus disease (COVID-19)
Publisher: European Archives of Oto-Rhino-Laryngology
Publication Date: April 2, 2020
URL: https://link.springer.com/content/pdf/10.1007/s00405-020-05965-1.pdf
Key Takeaway: Sudden anosmia or ageusia may occur without typical symptomatology, warranting testing.
Title: Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young
Publisher: New England Journal of Medicine
Publication Date: April 28, 2020
URL: https://www.nejm.org/doi/full/10.1056/NEJMc2009787
Key Takeaway: 5 cases of patients under 50, with large-vessel CVA’s and COVID-19. A 7-fold increase from usual.
Title: CDC- Updated Guidance: Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19)
Publisher: Centers for Disease Control and Prevention
Publication Date: April 27, 2020
URL: https://www.cdc.gov/coronavirus/2019-ncov/index.html
Key Takeaway: This updated CDC recommendation adds chills, rigors, myalgias, headache, sore throat and new loss of taste or smell to the original case definition of clinical Covid-19 disease that had been previously defined as fever, cough and SOB.
Therapeutics
Title: Practical strategies for a safe and effective delivery of aerosolized medications to patients with COVID-19
Publisher: Respiratory Medicine
Publication Date: April 21, 2020
URL: https://www.sciencedirect.com/science/article/pii/S095461112030127X
Key Takeaway: Recommendations for use of nebulizers in COVID-19 patients
Title: Points to consider in the preparation and transfusion of COVID-19 convalescent plasma
Publisher: International Journal of Transfusion Medicine
Publication Date: April 22, 2020
URL: https://doi-org.proxygw.wrlc.org/10.1111/vox.12939
Key Takeaway: Guide to drawing and administering convalescent plasma
Title: PRESS RELEASE - NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19 - DATA UNDER REVIEW - NOT YET PUBLISHED
Publisher: NIH, NIAID
Publication Date: April 29, 2020
Key Takeaway: Preliminary results from Remdesivir RCT
Title: NIAID Covid-19 Treatment Guidelines
Submitted by: US National Institutes of Health
Publication: April 21, 2020 (continuously updated)
URL: https://covid19treatmentguidelines.nih.gov/
Key Takeaway:
hydroxychloroquine and azithromycin in combination (due to risk of toxicity), lopinavir/ritonavir or other HIV protease inhibitors, interferons, Janus kinase inhibitors.
Title: Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19
Publisher: New England Journal of Medicine
Publication: April 23, 2020
URL: https://www.nejm.org/doi/full/10.1056/NEJMsr2005760
Key Takeaway:
● There are theoretical considerations that ACE inhibitors or ARBs may influence the infectivity of SARS-CoV-2. However, these drugs have established benefits in protecting the kidney and myocardium, and their withdrawal may risk clinical decompensation in high-risk patients. In stable patients with COVID-19 they should be continued.
Title: COVID-19 and Thrombotic or Thromboembolic Disease: Implications for
Prevention, Antithrombotic Therapy, and Follow-up
Publisher: Journal of the American Journal of Cardiology
Publication: April 15, 2020
URL: http://www.onlinejacc.org/content/early/2020/04/15/j.jacc.2020.04.031
Key Takeaway:
Reports suggest unexpectedly common occurrence of venous thromboembolic disease in patients with severe COVID-19. This review summarizes the current understanding of the pathogenesis, epidemiology, management, and outcomes of this complication.
● Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.
Title: Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A Review, JAMA.
Publication: JAMA, April 13, 2020
URL: https://jamanetwork.com/journals/jama/fullarticle/2764727
Key Takeaway: This is a comprehensive review of scientific rationale and current status of pharmacologic treatments currently being studied or considered for treatment for patients with Covid-19 including:
Summaries and links to current clinical treatment guidance documents and an FAQ section is included. Bottom line: "No therapies have been shown effective to date."
Title: Infectious Disease Society of America (IDSA) Guidelines on the Treatment and Management of Patients with COVID-19 Infection
Publication: IDSA, April 12, 2020
URL: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
Key Takeaway: IDSA panel assessment and recommendations on current COVID treatments.
Recommendation 1. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends hydroxychloroquine/chloroquine in the context of a clinical trial.
Recommendation 2. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends hydroxychloroquine/chloroquine plus azithromycin only in the context of a clinical trial.
Recommendation 3. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends the combination of lopinavir/ritonavir only in the context of a clinical trial.
Recommendation 4. Among patients who have been admitted to the hospital with COVID-19 pneumonia, the IDSA guideline panel suggests against the use of corticosteroids. (Conditional recommendation, very low certainty of evidence)
Recommendation 5. Among patients who have been admitted to the hospital with ARDS due to COVID-19, the IDSA guideline panel recommends the use of corticosteroids in the context of a clinical trial.
Recommendation 6. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends tocilizumab only in the context of a clinical trial.
Recommendation 7. Among patients who have been admitted to the hospital with COVID-19, the IDSA guideline panel recommends COVID-19 convalescent plasma in the context of a clinical trial.
Title: Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)
Publication: April 11, 2020 (not peer-reviewed)
URL: https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1
Key Takeaway: In this Phase IIb double-blinded RCT study conducted in Brazil, the high dose (600 mg) BID chloroquine arm was halted early due to a high rate of cardiac side effects. The high dose CQ arm presented more QTc>500ms (25%), and a trend toward higher lethality (17%) than the lower dosage. Fatality rate was 13.5% (95%CI=6.9-23.0%), overlapping with the CI of historical data from similar patients not using CQ (95%CI=14.5-19.2%). Study halted as no benefit and significant risk of harm were evident.
Title: Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial
Publication: April 14 (not peer-reviewed)
URL: https://www.medrxiv.org/content/10.1101/2020.04.10.20060558v1
Key Takeaway: The administration of HCQ did not result in a higher negative viral conversion rate (positive to negative test) but more alleviation of clinical symptoms than SOC alone in patients hospitalized with COVID-19 without receiving antiviral treatment, possibly through anti-inflammatory effects. Very few patients with severe disease were included. Adverse events were significantly increased in HCQ recipients but no apparently increase of serious adverse events.
Title: Virological and Clinical Cure in COVID-19 Patients Treated with Hydroxychloroquine: A Systematic Review and Meta-Analysis
Publication: Journal of Medical Virology, April 16, 2020
Web site: https://www.ncbi.nlm.nih.gov/pubmed/32297988
Key Takeaway: This reports on a systematic review of 16 literature databases out of which seven studies (n=1358) were included to summarize the virologic and clinical use of hydroxycholorquine to treat Covid-19 disease concluding that hydroxychloroquine may decrease risk of radiological progression without increased adverse events when compared to other treatment options, including no treatment at all. Despite the radiologic progression, no difference was observed in virological cure, death or clinical worsening of disease when compared to the control or conventional treatment.
Title: Considerations for drug interaction on QTc in Exploratory Covid-19 Treatment
Web Address: https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.047521
Key Takeaway: Joint Statement by American Heart Association and American College of Cardiology. This letter recommends specific monitoring to minimize risk of adverse drug reaction when using chloroquine-based treatments for Covid-19 infection. April 8, 2020
Title: Effectiveness of convalescent plasma therapy in severe COVID-19 patients
Web Address: https://www.pnas.org/content/early/2020/04/02/2004168117
Key Takeaway: This is a report on the immunologic and clinical endpoints of 10 patients with severe Covid-19 infection who were treated with convalescent plasma derived from recently recovered donors. April 6, 2020.
Title: AAMC COVID-19 Clinical Guidance Repository
URL: https://www.aamc.org/covid-19-clinical-guidance-repository
Key Takeaway: The AAMC COVID-19 Clinical Guidance Repository includes content from academic medical centers as a resource for hospitals and clinicians across the United States. The goal is to identify, summarize, and highlight areas of alignment in clinical practice during the
Title: No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection
Key Takeaway: This study of hydroxycholoroquine and azithromycin used in patients with Covid-19 shows no viral or clinical benefit. This study contradicts an earlier study that reported clinical benefit. Both studies are non-randomized and the patients treated have different
Title: GW Division of Infectious Diseases - Covid - Recommendations on Use of Cholorquine-Hydroxychloroquine
URL: https://drive.google.com/open?id=1YF2YQ7ujlFY7IJOf0oAdRaR1Vtw3qbnx
Key Takeaway: This is guidance from GW's ID Division on use of Cholorquine-Hydroxychloroquine for treatment of patients with Covid-19.
Ventricular Arrhythmia Risk Due to Hydroxychloroquine-Azithromycin Treatment For COVID-19
ACE Inhibitors
Treatment Review
Convalescent plasma
