Weekly Update, 5/7-5/14

Four Covid-19 Updates for the Week of May 7-14

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1) CDC Updates Guidelines for Discontinuing Isolation in Persons with COVID-19

For individuals recovered from COVID-19 illness, the CDC has increased the recommended period of isolation from 7 days to 10 days after illness onset and at least 3 days after recovery. The CDC defines illness onset as the date symptoms begin. Recovery is defined as resolution of fever without the use of fever-reducing medications with progressive improvement or resolution of other symptoms. Ideally, isolation should be maintained for this full period to the extent that it is practicable under rapidly changing circumstances.

 2) COVID-Associated Coagulopathy

It is now clear from multiple studies that 10-43% of patients with COVID-19, especially those who are critically ill, are hypercoagulable. The exact number is not well elucidated. Studies differed with variations in severity of illness presentation among patients.

This hypercoagulability results in both arterial and venous thromboses. It has been known almost from the start of the epidemic that an elevated d-dimer in COVID-19 patients is a marker for poor outcomes since the d-dimer is a marker for ongoing thrombosis. The thrombotic complications seen in COVID-19 include deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, acute coronary syndrome (ACS)/myocardial infarction (MI), limb ischemia and gastrointestinal (GI) ischemia.  There are also reports of cardiac valve clots. 

Patients with COVID-19 associated coagulopathy generally have normal clotting studies (aPTT, PT/INR) but may have an elevated aPTT reflecting an anticardiolipin antibody/lupus-like anticoagulant (90% in one series of those with an elevated aPTT).  Unlike in disseminated intravascular coagulation (DIC), hypercoagulable COVID-19 patients often have normal or slightly high platelet counts and high fibrinogen. These patients are hypercoagulable despite the elevated aPTT and should be anticoagulated as per standard of care. 

There is consensus that “all” patients admitted to the hospital should be treated with prophylactic-dose heparin (e.g. enoxaparin or others) and should have a low threshold for evaluation of blood clot (e.g. chest CT, extremity doppler, etc.).  If a patient is deteriorating and CT for PE will be delayed, it is reasonable to start full anticoagulation while awaiting study results, balancing treatment with consideration of bleeding risk.

Some institutions are starting full-dose anticoagulation on critically ill patients without known clot, which remains controversial.

NEJM May 5, 2020 DOI: 10.1056/NEJMc2013656
Abdominal Visceral Infarction in 3 Patients with COVID-19 https://wwwnc.cdc.gov/eid/article/26/8/20-1161_article?deliveryName=USCDC_333-DM28184
Journal of Thrombosis and Heamostasis,  https://onlinelibrary.wiley.com/doi/10.1111/jth.14888

3)   In Vivo Human Monoclonal Antibodies

A study reported the discovery of human monoclonal antibodies that neutralize  SARS-CoV-2 (and SARS-CoV) in cell culture.  While there is currently no vaccine that can prevent the disease, this monoclonal antibody could potentially offer future prevention and treatment.  This is not clinically available at present, but the finding indicates that effective neutralizing antibodies can be identified as they target a communal epitope on the virus, thus increasing the probability of an effective vaccine being identified.

Wrapp et al., Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies, Cell (2020), https://doi.org/10.1016/j.cell.2020.04.031

Wang, C., Li, W., Drabek, D. et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun 11, 2251 (2020). https://doi.org/10.1038/s41467-020-16256-y

4)   Another bad week for hydroxychloroquine

Another week, another negative study of hydroxychloroquine in COVID-19.  This is a study of 1446 consecutive patients admitted for COVID-19 excluding those who were intubated, died, or were discharged within 24 hours.  Outcomes were intubation or death in a time-to-event analysis.  Propensity scoring was used to adjust the data for disease severity, smoking, etc. They also did a multiple sensitivity analyses to test the robustness of their results. There was no difference between intubation plus death between the placebo and treatment groups (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32).

NEJM May 7, 2020 DOI: 10.1056/NEJMoa2012410


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