Weekly Update: August 26 - September 1st

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This week we have more information about anticoagulation in patients with COVID-19, a controversy about who to test after an exposure to COVID-19, information on the expanded use of remdesivir, and the ocular manifestations of COVID-19 in children.

Routine prophylactic anticoagulation seems to be of benefit in those hospitalized with COVID-19. This is a retrospective study of either prophylactic, full dose or no anticoagulation in 4389 patients >18 years of age admitted for COVID-19 at 5 hospitals in New York. Exclusion criteria included discharge within 48 hours of admission, being treated with both full dose and prophylactic dose anticoagulation during the hospitalizations, or <48 hours of anticoagulation.
The outcome was in hospital mortality with a secondary endpoint of intubation. They tried to adjust for other variables including history of hypertension, BMI, chronic kidney disease, etc.
The risk of death or intubation was lower in those on either full dose or prophylactic dose anticoagulation (HR 0.53 (95%CI 0.45-0.64 and HR=0.50 95% CI 0.45-0.57 respectively). Bleeding was 3.0% with full anticoagulation and was about half this in the no anticoagulation and prophylactic anticoagulation groups. In a subgroup analysis, there was no difference between the full dose and prophylactic dose heparin, if started within 48 hours of admission.
This was a retrospective study, but suggests that early prophylactic therapy with heparin reduces mortality and that low dose is equivalent to full dose anticoagulation. The bleeding risk seems acceptable. More information on full dose anticoagulation, when it arrives will be welcome. As is the case with many of these trials, it isn’t randomized so cannot give us a definitive answer; one cannot control for every variable. It does, however, suggest that prophylactic dose anticoagulation is helpful.

Nadkarni, GN et al. Mortality, Bleeding and Pathology Among Patients Hospitalized with COVID-19: A Single Health System Study J Am Coll Cardiol. 2020 Aug 26. Epublished DOI:10.1016/j.jacc.2020.08.041

The FDA has authorized remdesivir for patients with all severities of COVID-19 disease. The emergency authorization document can be found here. This is based on the study that we covered last week, the discussion which can be found here. In that study the authors concluded that “Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance.” The salient points are:

  • The FDA finds “it is reasonable to believe that remdesivir (Veklury) may be effective”.
  • The FDA is “no longer limiting its (remdesivir) use to the treatment of patients with severe disease.”

We really don’t know if this will help the clinical (not statistical) situation of patients. As with most things COVID-19, we are waiting for more data.

FDA Authorization Document: https://www.fda.gov/media/137564/download

Spinner, CD et al. Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients with Moderate COVID-19A Randomized Clinical Trial JAMA. Published online August 21, 2020. doi:10.1001/jama.2020.16349

Saliva based PCR performs as well or better than nasopharyngeal (NP) swab- based PCR.This is as study in two parts. In the first phase, 70 inpatients with known COVID-19 by NP swab were tested using a saliva sample. The testing showed “more” copies of SARS-CoV-2 RNA in saliva when compared to the NP specimens (the confidence intervals overlap, however). Ten days post infection “more” of the saliva tests were positive (81% vs. 71%, but again the confidence intervals overlap).
In the second part of the study, they screened 495 asymptomatic health care workers using both saliva and an NP swab. They found 13 individuals without symptoms who tested positive, confirmed by a second test. The NP swab was negative in 7 of them.
This is not the “rapid” antigen saliva test that has been in the news recently. All of these were done by PCR.  However, a saliva-based test may be more acceptable to patients and may yield more uniformity in specimen collection (you don’t have to have an uncomfortable NP swab specimen that may or may not be adequate). This study suggests that the saliva test is at least as good as using an NP swab.

Wyllie AL et al. Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2 NEJM August 28, 2020 DOI: 10.1056/NEJMc2016359

 Confusion about who to test. This week the CDC suggested that asymptomatic individuals with COVID-19 exposure need not be tested. This was subsequently dialed back but this clarification has not been changed on the CDC website. We are reposting the summary of the AMA guidelines for testing and a link to the AMA’s recommendations.
The American Medical Association (AMA) has released testing recommendations since testing is likely going to be limited, at least through the remainder of 2020. They point out that the supply of swabs is finally adequate but that reagents, viral transport media, pipette tips and other testing paraphernalia are still in short supply.

 They recommend prioritizing testing for high risk individuals:

  • Patients exhibiting signs/symptoms of COVID-19
  • Those with a known exposure to COVID-19 (e.g. as in contact tracing).
  • Those required to have a negative COVID-19 test in order to get needed medical care such as elective surgery, chemotherapy, etc.
  • Health care workers

A second tier would be those not at immediate risk of infection, including:

  • Those wishing to travel
  • Those wishing to attend social engagements

Those returning to work or school.
They emphasize counseling those being tested to stay quarantined until the results are reported, and a negative test is confirmed. The full statement can be found here.

AMA Public Health, Considerations for physicians ordering SARS-CoV-2 PCR diagnostic testing. https://www.ama-assn.org/delivering-care/public-health/considerations-physicians-ordering-sars-cov-2-pcr-diagnostic-testing

Finally, and briefly, ocular symptoms may occur in youngsters with COVID-19 who are otherwise asymptomatic. This is a limited series but worth raising awareness. In this series, 22% of children with COVID-19 had some ocular finding (eye rubbing, discharge, redness, etc.). More importantly, 4% of children had ocular symptoms as their initial presentation.
This does not mean we should test all children with eye symptoms for COVID-19, but we should at least ask a question about exposure.

Ma, N et al. Ocular Manifestations and Clinical Characteristics of Children With Laboratory-Confirmed COVID-19 in Wuhan, China JAMA Ophthalmol. Published online August

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