COVID-19 Update May 26th, 2020 by Dr. Andrew Morris
Edited by Anton Helman
Epidemiology and Prevention of COVID-19
We have no idea how to prevent COVID-19 with non-pharmaceutical interventions (NPIs), but it is clear that jurisdictions that have effectively pursued a test, trace, isolate approach combined with physical distancing and mask-wearing can get COVID-19 under control. Those that cannot do not get COVID-19 under control. As it stands, there are no effective pharmaceutical interventions for COVID-19. Perhaps the most hotly pursued was hydroxychloroquine prophylaxis. We await the clinical trials. I will discuss treatment later on.
If we talk about acquisition of disease, the epidemiology has been fairly consistent: the highest risk comes from prolonged, close contact, indoors, unmasked, ideally with shared surfaces or food. So household contacts are important, but there have been several high-profile outbreaks, including the well-described choir practice, where 61 people attended a 2.5h choir practice where there was one symptomatic person, with an attack rate of 53-87%, resulting in 3 hospitalizations and 2 deaths.
What becomes less clear is the role of children in disease acquisition and transmission. Epidemiologists struggle with this a bit, because children are long believed to be the source of respiratory viral evil: looking cute and cuddly, but in fact being quite deadly with all sorts of germs. We know that there have been no childhood deaths in Canada. In fact, despite over 5M infected and 343 513 deaths, children are massively under-represented. There have been several prior attempts to quantify this, and much of it is very reassuring. In Europe, only about 2% of all lab-confirmed cases were under age 15. However, this one recent report from a tertiary centre in New York City, posted online May 11, describes a somewhat uneasy picture: 46 admitted patients, of which 13 were admitted to the PICU—8 were discharged home, 4 remained on a ventilator at Day 14, and 1 (with metastatic cancer) died.
Further with children, we are starting to learn more about the PIMS-TS (dyslexically labelled Pædiatric Multisystem Inflamatory Syndrome Temporally associated with SARS-CoV-2) or Multisystem Inflammatory Syndrome in Children (MIS-C), which is the Kawasaki-like disease that appears associated with COVID-19. It is characterized by fever, inflammation, organ failure, and SARS-CoV-2 infection, but may have headache; sore throat, cough, or other respiratory symptoms; conjunctivitis; lymphadenopathy; rash; abdominal pain, vomiting and/or diarrhea; and characteristic swelling and/or redness of the hands and feet (referred to as chilblain). The fascinating thing is that it appears to be disappearing. Regardless, it is incredibly rare, with the European CDC reporting recently that there have only been 230 suspected cases of PIMS-TS in the European Union or UK, where there are over 80 million children.
Whether or not we need N95 masks for prevention—and where we need them—continues to remain a controversy for reasons unclear to me (https://www.cidrap.umn.edu/practice/facemask-and-n95-respirator-recommendations). Perhaps a more fascinating story is the position of the Royal College of Dental Surgeons of Ontario, who have decided that the typical dental office needs to wait 207 minutes (yup, 207) between patient appointments before cleaning a dental operatory.
Diagnosis of COVID-19
Diagnosis hasn’t advanced substantially. We remain beholden to the RT-PCR via nasopharyngeal swab. Just a couple of weeks ago, the FDA approved the home-collected Rutgers Clinical Genomics Laboratory test (LDT) using the Spectrum Solutions LLC SDNA-1000 Saliva Collection Device. The FDA has not had the most auspicious tract record on regulation lately, so whether this device is the real deal or not remains to be seen.
We still seem to be relying, in the acute setting, on a variety of PCR tests.
Whether or not someone has been infected (i.e. using serology) has been a story of 1 step forward and 2 steps back. There are a variety of different tests: rapid diagnostic test (uses a lateral flow assay as a point-of-care rest), ELISA, neutralization assays, and chemiluminescent immunoassay. Eleven such tests have been approved in the US, whereas there is only 2 approved in Canada: the LIAISON test, developed by DiaSorin (an Italian biotech) and the SARS-CoV-2 IgG assay by Abbott; an additional 22 serological tests are at various stages of approval by Health Canada.
Treatment of COVID-19
Hydroxychloroquine (HCQ) continues to take a beating. This study in mild-moderate COVID-19 failed to show a benefit in 148 patients randomized to HCQ vs. standard of care. There was no apparent microbiological benefits, with 30% of HCQ patients getting side effects vs. 9% of those receiving standard care. (Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:m1849.) Similarly, an observational study published in The Lancet looked at 96,032 patients hospitalized with COVID-19, with 1,868 receiving chloroquine, 3,783 CQ + macrolide, 3,016 receiving HCQ, and 6,221 receiving HCQ + macrolide (Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. The Lancet. 2020.) It really doesn’t matter how you dice this study up, it is an observational study that does not favour CQ or HCQ. We need a bigger and better RCT.
Most of the attention this past week rested on remdesivir. More than 3 weeks after Dr. Fauci of the NIH stated publicly that remdesivir should be the standard of care, it was released online by the NEJM in what is quite remarkable: preliminary results of the halted trial. What did we learn? Well, this was an RCT of 1059 patients—538 assigned to remdesivir and 521 to placebo—with a median recovery time of 11 days in the remdesivir arm and 15 days in the placebo arm. Using Kaplan-Meier estimates of 14 day mortality, 7.1% of those on remdesivir died vs. 11.9% on placebo; adverse events favoured remdesivir. Perhaps more striking: the benefit was not seen in those receiving high-flow oxygen, non-invasive mechanical ventilation, mechanical ventilation, or ECMO. So what to do with all of this? Well, it stands in relief to the much smaller Chinese trial published in The Lancet with 237 patients that showed no difference in time to clinical improvement overall, but DID show a reduction in time to clinical improvement in those treated early. (Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet. 2020;395(10236):1569-78.) Additionally, it appears that—once you get really sick, it is of minimal benefit. This is problematic because it is administered intravenously, and what it does is gets you better quicker, but it might not make an overall difference to your outcome. I really wish they didn’t stop this trial yet. I am hopeful the WHO’s SOLIDARITY trial (with its Canadian CATCO arm) gives us more clarity.
References for COVID-19 update
- Hamner L, Dubbel P, Capron I, et al. High SARS-CoV-2 Attack Rate Following Exposure at a Choir Practice – Skagit County, Washington, March 2020. MMWR Morb Mortal Wkly Rep. 2020;69(19):606-610.
- Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:m1849.
- Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. The Lancet. 2020.
- Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 – Preliminary Report. N Engl J Med. 2020;
- Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet. 2020;395(10236):1569-78.