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COVID-19 Intelligence Report: Therapeutics (drugs/treatments)

June 29, 2020

  • Tocilizumab
    • A retrospective case-control study of patients with severe COVID-19 found a non-statistically significant lower mortality in the treatment group (52% versus 62.1% P = 0.09). When excluding intubated patients, there was statistically significant lower mortality in patients treated with tocilizumab (6% vs. 27% P = 0.024).
    • A 21-day observational study published in CHEST found that in tocilizumab-treated patients, oxygenation and inflammatory biomarkers (hsCRP and IL-6) improved. However, sIL-2R and D-Dimer levels increased. Survival of severe patients treated with tocilizumab was similar to non-severe patients: (83% vs 91%; p=0.11).
    • A retrospective, observational cohort study found that in patients with severe COVID-19 pneumonia, treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death
      • Tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0·61, 95% CI 0·40–0·92; p=0·020).
      • Follow-up for outcomes was brief - between 4-18 days.
  • Colchicine: Results from the GRECCO-19 randomized clinical trial found that participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. 

June 22, 2020

Key updates in treatment for COVID-19:

  • One RCT study found that among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment did not significantly improve the time to clinical improvement within 28 days. However, the study authors noted that the trial was terminated early and may have been underpowered to detect a clinically important difference.
  • Hydroxychloroquine sulfate (HCQ) and chloroquine phosphate (CQ) are no longer authorized by FDA to treat COVID-19. Further, FDA is warning health care providers that co-administration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended as it may result in reduced antiviral activity of remdesivir.
  • Massachusetts General Hospital published a new comprehensive resource for treatment of patients with COVID-19.
  • Researchers are beginning to learn why some patients with COVID-19 fare worse, identifying a genetic susceptibility locus and involvement of the ABO blood-group system. (Blood group A appears to lead to higher risk and blood group O may have a protective effect.)
  • Emerging evidence:
    • Preliminary results for an open label randomized controlled trial (RCT) in the United Kingdom found that dexamethasone can reduce mortality by one-third for ventilated patients and one-fifth for patients requiring only oxygen; there was no mortality benefit in patients on room air. These findings have not been peer-reviewed and were described pre-print in a press release.
    • Two studies have been released that suggest Anakinra may be a potential treatment: In one small, uncontrolled study using Anakinra 100mg every 8 hours the authors found rapid clinical improvement and a clinical trial is now underway. A second retrospective cohort study of non-ventilated patients with COVID-19 and ARDS found treatment with high-dose Anakinra (5 mg/kg IV BID) was safe and associated with clinical improvement in 72 percent of patients. At 21 days, survival was 90% in the high-dose Anakinra group and 56% in the standard treatment group.
    • One study in 100 patients, Tocilizumab infusion resulted in improved or stabilized clinical improvement at 10 days in 77 patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest X-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 patients, of whom 20 died.

June 15, 2020

Key updates in treatment for COVID-19: 

June 1, 2020

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.

May 25, 2020

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.

May 18, 2020

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.

May 11, 2020

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.

May 4, 2020

Title: Recent progress and challenges in drug development against COVID 

Publisher: Elsevier - Infection, Genetics and Evolution,

Publication Date: April 19, 2020

URLhttps://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

URLhttps://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

URLhttps://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

URLhttps://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-criteria.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

URLhttps://www.sciencedirect.com/science/article/pii/S095461112030127X     

Key Takeaway: Recommendations for use of nebulizers in COVID-19 patients

  • Mild Symptoms: Use MDI’s instead of nebulizers. If you must, use a mouthpiece instead of a mask. Use in negative pressure rooms, and use filters on the tubing and mouthpiece when possible.
  • Sub-ICU: Use high flow, and deliver aerosol via high flow early. Administer in negative pressure rooms. Put a surgical mask over the mouth and nose of the patient.
  • ICU: Use mesh nebulizers (all other neb-types require breaking the circuit) and HEPA filter to expiratory tube.

 

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

URLhttps://doi-org.proxygw.wrlc.org/10.1111/vox.12939     

Key Takeaway: Guide to drawing and administering convalescent plasma

  • Need a clear timeline and good tests. Wait 14 days following full recovery. Minimize transfusion related lung injury (TRALI) by preferring men or never-pregnant females (occurs within 6 hrs).
  • Use viral inactivator washes. Freeze asap.
  • Can use multi-donor plasma.
  • Initial dose of 200ml.

 

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

URLhttps://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19     

Key TakeawayPreliminary results from Remdesivir RCT

  • Hospitalized patients with advanced COVID-19 and lung involvement who received remdesivir recovered faster than similar patients who received placebo.
  • 68 sites, most in US, with others in Europe and Asia; 1063 patients
  • Trial was stopped by the Data and Safety Monitoring Board for efficacy
  • For severe cases, time to recovery 31% faster – 11 vs 15 days was statistically significant.
  • Results also suggest a survival benefit - not statistically significant (8% mortality for treated vs 11.6% placebo)
  • Manuscript under review - not yet published so complete data are not available.

April 27, 2020

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: 

  • At present, no drug has been proven to be safe and effective for treating COVID-19. There continue to be no FDA-approved drugs specifically for COVID-19. These recommendations will be updated frequently as new trial data emerges. 
  • There are insufficient clinical data to recommend either for or against use of the following: hydroxychloroquine or chloroquine, remdesivir, convalescent plasma, IL-6 inhibitors (e.g. sarilumab, tocilizumab), or IL-1 inhibitors (e.g., anakinra). 
  • The following should be given only as part of a clinical trial, or avoided:

hydroxychloroquine and azithromycin in combination (due to risk of toxicity), lopinavir/ritonavir or other HIV protease inhibitors, interferons, Janus kinase inhibitors.   

  • Recommendations for critical care, and concomitant medications, are also provided.  

 

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.

April 20, 2020

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:

  • Chloroquine/hydroxychloroquine
  • Antiretrovirals (Kaletra and others)
  • Remdesivir and Favipiravir
  • Corticosteriods
  • ACE inhibitors
  • Immune modulators
  • Immunoglobulin therapy

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.

April 9, 2020

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. 

April 5, 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

URL: http://proxygw.wrlc.org/login?url=https://www.sciencedirect.com/science/article/pii/S0399077X20300858

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.

April 4, 2020

Ventricular Arrhythmia Risk Due to Hydroxychloroquine-Azithromycin Treatment For COVID-19

  • https://www.acc.org/latest-in-cardiology/articles/2020/03/27/14/00/ventricular-arrhythmia-risk-due-to-hydroxychloroquine-azithromycin-treatment-for-covid-19#.XoaHk6IoOso.email 
  • This article proposes clinical guidelines and risk stratification for addressing safety of use of this unapproved approach to Covid-19 treatment.  Chloroquine or hydroxychloroquine in combination with azithromycin have been proposed for Covid-19 treatment. This is not an FDA-approved approach. Each medicine prolongs the QT interval, raising concerns about the risk of arrhythmic death from individual or concurrent use of these medications.   Hydroxychloroquine or chloroquine therapy should occur in the context of a clinical trial or registry, until sufficient evidence is available for use in clinical practice. 
  • Hydroxychloroquine or chloroquine use outside of a clinical trial should occur at the direction of an infectious disease or COVID-19 expert, with cardiology input regarding QT monitoring. March 29, 2020

 

March 31, 2020

ACE Inhibitors

  • https://jamanetwork.com/journals/jama/fullarticle/2763803
  • Patel AB, Verma A. COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? JAMA. Published online March 24, 2020.
  • Note from submitter: JAMA Viewpoint article on use of ACE and angiotensin receptor blockers in patients with Covid-19. 

Treatment Review                       

Convalescent plasma                               

  • https://jamanetwork.com/journals/jama/fullarticle/2763983
  • JAMA Preliminary Communication: Treatment with convalescent plasma.
  • Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4783
  • Note from submitter: JAMA Preliminary Communication: Treatment with convalescent plasma.

Other Resources

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