COVID-19 Interest Group
November 25, 2020
CIG Bulletin #22
Remdesivir (by Pate Thomson)
Underlying Causes of the Surge (by Tina Etcheverry)
Do you remdesiver, my darling? By Pate Thomson
What should we make of conflicting results from two major studies of Remdesivir?
This drug was originally chosen because it inhibited SARS CoV-2 in vitro. The study was conducted by the NIH and under auspices of Institute of Allergy and Infectious Disease(NIAID), and reported preliminarily in May and finally on Nov 5. The study was, rigorous, randomized, placebo controlled and double blinded and it involved 1062 patients split almost evenly between placebo and drug treated group. It showed shorter time to recovery (5 days shorter), improved clinical status and it may have prevented progression to more severe respiratory disease. There was an improved mortality trend that did not reach statistical significance. The group most benefited were those who received treatment who were not requiring a ventilator at the time of selection. The conclusion of this study was that there was a measurable modest benefit and that this was enough for the data review board to permit unblinding in order to permit treatment of the placebo group. Ultimately, on 10/22/20 the FDA approved use of Remdesivir for treatment of Covid-19.
In the larger study, preliminarily reported in October, conducted by the WHO, involves 405 hospitals, in 30 countries, and 11,221 patients. There was a difference in primary end points and there are many differences in the study design. It was open label (not blinded), with randomized allocation to one of four drugs with 2750 patients receiving Remdesivir and 2708 in standard treatment control. It concluded that there was no meaningful effect on survival and no shortening of the time to recovery. It has not yet been peer reviewed.
After convincing myself that there was not likely to be manipulation of this NIH data by political influences, and because no one knows how to better design a study than the NIH NIAID group, I am throwing my hat into the yes on Remdesivir group, recognizing that the benefit is likely to be small. So how would we explain the Solidarity Trial results? It seems plausible that the difference in trial design, small effect of the drug, and the complexity of managing the much larger WHO trial could explain failure of a small benefit to show up.
Yes my dear, I do remdesivir.
Editor comment: The success of the earlier study by NIH/NIAID suggests that timing of dosing is everything. Patients need to be treated with Remdesivir early in the course of infection (such as the treatment President Trump received) and it will then block progression to more serious complications. By the time a patient reaches the ICU with full blown disease, this drug will not show much benefit. Yes my dear, I agree.
What does the surge mean? By Tina Etcheverry
We are now experiencing the highest rate of coronavirus infection across the United States. The percent of people testing positive has increased since September to 11% - eclipsing the rate we saw earlier this summer. Three regions in the U.S. are especially showing positivity in all age groups – Midwest, Central and Mountain regions (cdc.gov). All age groups that seek outpatient services are showing increases, but the 25-49 year old grouping stands out since it is increasing the fastest. The theory is that they are socializing more, eating in restaurants and visiting bars, and some have returned to work.
Why are we seeing this trend?
Humans are social creatures. We are experiencing fatigue from social isolation. With the onset of colder weather, and early darkness, people are engaging more in indoor social gatherings. When indoors, they are more likely to not wear masks or keep appropriate social distances. Gatherings in restaurants and bars, indoor recreational facilities, faith based religious meetings, Trump rallies, and Halloween parties are all contributing to the spread of the virus. People leave these social gatherings and bring the virus home, leading to household spread.
Contact tracing is trying but can hardly keep up with this new rate of spread. In Oregon, there were 5 large Halloween parties that lead to super spreading of the virus in four communities. The Sturgis motorcycle rally in August (450,000 attendees) led to cases all over the mid-west. One study in Minnesota by using nucleic acid sequencing, traced a variant of the virus from Sturgis into Minnesota, and these investigators estimate that 1/3 of the cases in Minnesota are related to the motorcycle rally.
Bottom line is that social gatherings are leading to viral infections within the respective households. Let’s stay home, and stay safe! Only you can prevent corona-spread.