COVID-19 Science, News, and Research Weekly Briefings, August 16, 2021

August 16, 2021 Weekly C19 Briefing summary: Cloth and surgical masks are minimally helpful; FDA approves mAb therapy for prophylaxis and approves boosters for immunocompromised (and the booster shots are working); Moderna offers better protection than Pfizer against Delta; new quarantine periods for Delta depend on whether or not the patient has been vaccinated; more data show the vaccines do not impact fertility; if Florida were its own country, it would have the 5th highest rate of C19 in the world; HHS workers must get vaccinated or lose their jobs; higher circulating antibody levels are what prevents infections while durable B and T cells prevent severe disease during the viral phase. 

927.  The quality of the mask is important.  20% protection with cloth masks, 40% with surgical masks, 95% with the masks we are wearing.  Vaccinated people are having a shorter disease period and spreading the disease less than unvaccinated people; they tend not to be superspreaders but confine their spread to household members.
https://www.cnbc.com/2021/08/09/dr-scott-gottlieb-says-the-covid-delta-surge-may-be-the-final-wave-in-us.html
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928.  The FDA authorizes use of mAbs for prophylaxis in people with known exposure. 
​https://www.empr.com/home/news/fda-authorizes-use-of-covid-19-antibody-therapy-for-postexposure-prophylaxis/

929.  In a study of more than 50,000 patients in the Mayo Clinic Health System, Moderna's effectiveness dropped from 86% effectiveness against infection against Alpha to 76% against Delta (Jan/Feb vs. July).  Over the same time period, the effectiveness of Pfizer dropped from 76% to 42%.
​https://www.medrxiv.org/content/10.1101/2021.08.06.21261707v1.full.pdf

930.  Among 198 residents in a long term care home, stronger immune responses were mounted following Moderna than Pfizer, with higher levels of total and neutralizing antibodies after Moderna.
https://www.medrxiv.org/content/10.1101/2021.08.06.21261721v1

931. More great epidemiological work from the UK: the REACT study evaluates population-level info to reveal where, how, and which variant of Scov2 is spreading. We have no similar effort here.  The CDC’s cohort studies are small, narrow, and occasional.  We are still not investigating breakthrough cases unless they result in severe disease or death.  This website is worth perusing–it's a treasure trove of real time data.  One new data point: Delta infections cause longer viral shedding than prior variants.
https://www.imperial.ac.uk/medicine/research-and-impact/groups/react-study/real-time-assessment-of-community-transmission-findings/

932.  Viral loads decline more rapidly in vaccinated (mRNA) vs. unvaccinated people infected with Delta.  Vaccinated reached a Ct value of 30 on day 9 post-diagnosis vs. day 15 for unvaccinated.  If we use Ct as a surrogate for infectiousness with the assumption that a Ct value of 30 or more means viral titers have dropped low enough to make the disease no longer transmissible, we should consider amending our current quarantine instructions as follows: 10 days for vaccinated; 16 days for unvaccinated (from on set of illness covid-19-science-news-and-research-weekly-briefings-august-16-2021.html or date of positive test).
https://www.medrxiv.org/content/10.1101/2021.07.28.21261295v1

933.  Neither infection nor mRNA vaccination causes any harm to eggs or ovarian follicles.
https://academic.oup.com/humrep/advancearticle/doi/10.1093/humrep/deab182/6345462?searchresult=1

934.  As Delta rips through Florida (one in every five cases in the country is currently taking place in Florida), the Governor of that state has issued an executive order banning mask mandates for kids in schools and threatening to withhold teacher salaries if schools require masking.  The CDC, the American Academy of Pediatrics, and other major health organizations and leading experts are all in agreement that masking is critical for safety as the case rates among kids rises exponentially due to Delta.  Now, >800 doctors sign a letter criticizing what is clearly a political–not rational, science-based–anti-masking position.
https://www.independent.co.uk/news/world/americas/us-politics/ron-desantis-florida-doctor-petition-b1901724.html

935.  The WHO is conducting a clinical trial in 52 countries to study 3 anti-inflammatory drugs as potential treatments for hospitalized C19 patients: artesunate, imatinib and infliximab.  The primary endpoint will be death.  This will be part of the Solidarity PLUS trial.  Artesunate is already used for malaria, imatinib for certain cancers, and infliximab for autoimmune diseases such as Crohn's Disease and RA.  The original Solidarity trial last year found that all 4 treatments evaluated - remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon - had little or no effectiveness against C19.  Unfortunately, they did not include colchicine which has shown a strong signal from the data that it could prevent hospitalizations....  
https://www.who.int/news/item/11-08-2021-who-s-solidarity-clinical-trial-enters-a-new-phase-with-three-new-candidate-drugs

936.  HHS Secretary Xavier Becerra announced  today that vaccinations will be mandated for its workforce.  This will include employees of NIH and will affect > 25,000 employees, contractors, trainees, and volunteers whose duties put them in contact or potential contact with patients at an HHS medical or clinical research facility.  This comes on the heels of the Pentagon announcement earlier this week that by mid-September all 1.3 million military members would have to get vaccinated.  The U.S. Department of Veterans Affairs also announced a similar move last month and various airlines are moving in the same direction.  
https://www.politico.com/news/2021/08/12/hhs-mandates-covid-19-vaccinations-for-health-care-workforce-504138

​937. From NEJM: Confronting the catastrophe of long-covid/PCS.  C19 is not the first microorganism to cause long-term clinical sequelae but, perhaps because it is so much more widespread or perhaps because Scov2 enters cells through ACE2 and ACE2 is so ubiquitous, it is doing so at a much higher prevalence rate.  How will we deal with what looks very much like ME/CFS on a widespread scale?  Will we continue to marginalize these patients or treat their debilities as purely psychogenic?  My take: We will need more longitudinal studies like the one from the UK biobank showing a consistent pattern of gray matter destruction among C19 infected patients to help validate the suffering of long-haulers if they are going to be taken seriously by many healthcare providers.  If we do not do this, their care and management will be overseen by allied providers and fringe providers who are less well trained and less well equipped to take care of them.  
​file:///Users/gregoryberkoff/Downloads/Long%20code.pdf

939.  According to Shane Crotty at La Jolla Institute for Allergy and Immunology, after each exposure to a pathogen, the immune system conducts a kind of cost/benefit analysis on how robust and how durable post-infection immunity should be.  [My thought: The two-shot regimen is superior to the single dose regimen in part because the second exposure informs the immune system that the pathogen (or spike protein antigen) in question is highly prevalent.  We now know that the ideal spacing between doses for Pfizer is 8 weeks (see #901 from a previous briefing) and this could be one reason why Moderna, whose second shot is given at 4 weeks, is holding up better than Pfizer, whose second shot is at three weeks.]  Shane Crotty: A third exposure some months later via a booster is likely to make the immune response not only bigger (about twice the level of neutralizing antibodies is seen following the booster compared to that following the second dose of a two shot regimen) but also more durable as it informs the immune system that the pathogen (the spike protein) is prevalent and durable in the environment.  What's the best way to understand the relative roles of circulating antibody levels, memory B cells, and T cells?  Circulating neutralizing antibody levels are the line of defense that protects against infection.  With sufficient exposure, the virus will colonize in the mucous membranes of the nose, throat, mouth, and nasopharynx.  High levels of circulating neutralizing antibodies can quickly attack those (technically external) cells and stop the colonization from penetrating into the interior to cause an infection.  This, in my opinion, is the chief argument in favor of booster shots.  Memory B and T cells, on the other hand, form the primary arsenal of defenses once infection has occurred.  When the virus breaks through the epithelial level to enter the body's interior, helper T cells alert memory B cells and plasma cells to produce antibodies while killer T cells destroy infected cells and viruses contained therein.  This cell-mediated response takes a few days to mount, however, and with Delta replicating more quickly with a shorter incubation time, many breakthrough infections are symptomatic.  So far, we have seen that antibodies wane some months after infection or vaccination but T and B cells persist.  The durability of immune cells is what ensures that most vaccinated people will not progress to severe illness if they get infected; the waning of antibody titers over time means that months after primary vaccination or primary infection, the risk of breakthrough infections and reinfections increases.  If our focus is exclusively on the viral phase of C19, we do not need boosters yet.  If, however, we are also focused on the post-viral phase, then we need boosters to increase circulating antibody levels to help prevent infections.  Notice how Carlos Del Rio has to evade direct questions from Bob Wachter about what is clearly a need for boosters among those of us who got vaccinated half a year ago.  The focus is exclusively on the viral phase, as though the very subject of long-covid/PCS or the growing impressive data showing brain injury among those with even mild or asymptomatic infection, are taboo.  
https://www.youtube.com/watch?v=-sQsIETW47Q&ab_channel=UCSFSchoolofMedicine

940.  After a third shot (using Moderna) patients with organ transplants had a 71% neutralizing antibody protection against Scov2 compared with 13% among those who received the standard two dose regimen followed by placebo.  https://www.nejm.org/doi/full/10.1056/NEJMc2111462?query=featured_home941.  Elderly patients who waited 11-12 weeks for their second shot developed triple the antibody response compared to those who took the second shot at three weeks (Pfizer). 
https://www.medrxiv.org/content/10.1101/2021.05.15.21257017v1

942.  FDA approves boosters for limited group of immunocompromized patients under EUA, ahead of the CDC.  It looks like it will be a standard dose of either mRNA vaccine.  They are expected to give full certification of the vaccines (at least Pfizer and Janssen) in the next two weeks.  This would allow physicians to make their own decisions about when, which, how much, and to whom to give booster shots.  As yet, there is not guidance on timing in relation to other vaccines but I anticipate the recommendation will be to give at least a 30 days window.  
​https://www.nytimes.com/2021/08/12/us/covid-vaccine-booster-pfizer-moderna.html