Stay current with the emerging COVID-19 research including: ACTT-1 (remdesivir), triple therapy with interferon, and conundrums about SARS-CoV-2 PCR and serologic testing. We’re led by the one and only Curbsider/internist/epidemiologist, Rahul Ganatra MD MPH (@rbganatr). And…just in case you live outside of the habitat for murder hornets and your anxiety about the pandemic had begun to abate, we touch on the CDCs guidance to beware of hungry aggressive rats. Gross!
Written and Produced by: Rahul Ganatra MD, MPH, Deborah J. Gorth ScM, Emi Okamoto MD, Sarah P. Roberts MPH, and Matthew Watto MD
Cover Art: Deborah J. Gorth ScM
Hosts: Matthew Watto MD, Rahul Ganatra MD MPH, Emi Okamoto MD, and Sarah P. Roberts MPH
Editor: Matthew Watto MD (written materials); Clair Morgan of nodderly.com
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Both JAMA and the CDC have issued statements deemphasizing the spread of SARS-CoV-2 on fomites. JAMA’s new patient education page gives guidance about grocery shopping, so we can now stop bleaching our bread. The CDC re-organized its COVID advisory information page to seemingly downplay the risk of contracting COVID via contact with surfaces. However, per the CDC, the change was made simply to streamline content, and no new CDC guidelines have been issued regarding fomites and COVID transmission. The CDC did, however, recently issue a warning about the effect of COVID-19 on rodents, noting an increase in aggressive rat activity.
The ACTT-1 trial is a randomized, double-blind, placebo controlled trial testing the efficacy of intravenous remdesivir for hospitalized adults with COVID-19. The primary outcome for this study was positive; the remdesivir group recovered in 11 days (95% CI, 9 to 12) compared to 15 days (95% CI, 13 to 19) in the control group.
Hung et al investigates the effect of triple therapy with Lopinavir/Ritonavir, Ribavirin and interferon-beta on hospitalized patients with COVID-19. This is a multicenter, randomized, open-label, active controlled superiority trial with the primary outcome of time to negative nasopharyngeal swab. Patients in this study were not critically ill; only 15% of the patients were on supplemental oxygen, <5% were on non-invasive ventilator support, and only one patient in the study was intubated. In contrast with placebo-controlled trials, in an active-controlled trial, the control group receives another treatment, which was lopinavir/ritonavir in this study. The time to negative nasopharyngeal swab was 6.5 days for the triple therapy group and 12.5 days for the group treated only with lopinavir/ritonavir (p <0.0001). There was no difference in adverse events or mortality between the groups.
This trial provides evidence that treating patients hospitalized with mild COVID-19 with triple therapy reduces time to negative nasopharyngeal swab. As Rahul points out, this is only a surrogate endpoint, but it may have public health implications by reducing transmission of infection.
A polymerase chain reaction (PCR) is a method of selectively amplifying and measuring small portions of DNA using multiple cycles of warming and cooling to denature the DNA and a heat-tolerant DNA polymerase to copy the material. Real-time PCR (RT-PCR) is a quantitative PCR that uses the number of cycles to approximate the starting quantity of genetic material in relation to a reference. The PCR itself is specific and sensitive, but this test is limited by the quality of sample collected.
Kucira et al looked at 7 different studies and found that 67% of patients will test negative 4 days after exposure (i.e. one day prior to symptom onset), approximately 38% percent of patients will be negative on the first day of symptoms, and the lowest false negative rate is 3 days after symptom onset (20%). Prolonged viral shedding has been reported for up to 6 weeks, but no replication competent virus has been isolated after 10 days. The South Korean CDC released a report that suggests that individuals who have recovered from COVID-19, but still have a positive SARS-CoV-2 PCR did not infect new individuals.
False negative PCR testing for SARS-CoV-2 is common! Each patient must be evaluated based on symptoms, timing, and other relevant/available clinical information. Don’t assume that a negative PCR means the patient is free from infection.
Serological testing for the presence of antibodies is important for establishing prior exposure to SARS-CoV-2, verifying immune response for the development of vaccines, and potentially identifying individuals for plasma donation. A study by Bryan et al published in the Journal of Clinical Microbiology offered a promising characterization of an IgG antibody test. This test produced by Abbott for IgG antibodies against the SARS-CoV-2 nucleocapsid protein shows peak sensitivity and specificity of 100% for both at 14 days after PCR positivity and 17 days after symptom onset.
We believe that serologic testing will play an important role as we move forward during the pandemic, but at this time their clinical use is challenging since there are many different tests with different performance characteristics, antibody types and antigenic targets.
Listeners will practice their critical appraisal skills as they update themselves on the latest COVID-19 research.
After listening to this episode listeners will…
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Gorth DJ, Ganatra RB, Okamoto E, Roberts SP, Watto MF. “#217 COVID Cakes 4 the Fourth”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list. June 1, 2020.
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