August 26th, 2021

August 9, 2021 Weekly C19 Briefing summary: 

Local and national case rates continue to climb with 2,750 cases in one day (yesterday); vaccination protects against getting infected, lowering risk of catching C19 by 3-10x depending on the source; the FDA is expected to approve booster shots and certify Pfizer and Janssen very soon; herd immunity now estimated to be 90% of population immunized; the case rate among children is going up very fast; review of what we know about children and C19 and what we should be recommending; review of the new VOCs coming after Delta; the concept of 'leaky vaccines' is validated through a very well done new study.  

906.  There were 2,754 new cases yesterday in San Diego with a weekly average of more than 1,400/day.  This is almost certainly a significant undercount since Delta can cause a clinical picture that looks just like allergies or a cold with runny nose, sneezing, sore throat, and many people assume they have something that they "get all the time" or their doctors assume they have a cold.
https://www.nytimes.com/interactive/2021/us/san-diego-california-covid-cases.html 

907.  Although the MA team has doing PCR testing for some time, with new team members, I thought it would be good to review the technique for performing the swab which can make the difference between a positive test and a false negative test.  The key is to advance the swab along the floor of the nose toward the throat, not upward toward the brain.  Joyce, please make sure the entire team knows how to do this properly.  
https://www.youtube.com/watch?v=J7lLZEZ6u_w&ab_channel=NebraskaMedicineNebraskaMedicalCenter


908.  Vaccinated are 3x less likely to get infected than unvaccinated by the most current estimate from the REACT1 Study, in this paper from Imperial College London:
https://spiral.imperial.ac.uk/bitstream/10044/1/90800/2/react1_r13_final_preprint_final.pdf

909.  But 8x less likely to get infected according to Covid Tracker (Johns Hopkins University). 
https://www.covidtracker.com/

910.  And about 10x less likely to get infected according to the SDCDPH COVID-19 Watch. 
https://www.sandiegocounty.gov/content/dam/sdc/hhsa/programs/phs/Epidemiology/COVID-19%20Watch.pdf

911.  Two-thirds of people with mild or moderate viral periods (non-hospitalized) are still symptomatic 30-60 days after OOS: fatigue, SOB, and brain fog were the most common symptoms.  Yet another name for the syndrome is introduced in this paper as well: post-acute sequelae of SARS-CoV-2 or PASC.  
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254347

912.  The latest update on booster shots is that the FDA will likely approve them for immunocompromised under EUA in the next couple of weeks.  The FDA is also expected to approve Pfizer certification by the beginning of September.  If that happens, providers will be able to prescribe extra shots to whomever they think needs them.  
https://www.nytimes.com/2021/08/06/health/covid-booster-shot-immunocompromised.html?searchResultPosition=2

913. What is the number to reach herd immunity?  Because Delta is twice as transmissible as the D614G ancestral strain, the estimated threshold for herd immunity has been increased from 67% to 90%, according to the Infectious Diseases Society of America. 
https://www.idsociety.org/multimedia/videos/idsa-media-briefing-vaccines-the-delta-variant-and-chasing-herd-immunity/

914.  A booster dose of Novavax provided 4x the overall antibody levels and 6x greater functional ACE-2 binding inhibition antibodies against Delta than that observed shortly after the primary 2-dose vaccination series.  

https://ir.novavax.com/2021-08-05-Novavax-Announces-COVID-19-Vaccine-Booster-Data-Demonstrating-Four-Fold-Increase-in-Neutralizing-Antibody-Levels-Versus-Peak-Responses-After-Primary-Vaccination

915.  In the last week of July, children represented 19% of C19 cases in the US, representing a 25% jump from the prior average.  Cases among children doubled in the last week of July compared to the previous week.  This is likely due to Delta which is more transmissible, according to the American Academy of Pediatrics who recommends two things: children should return to school and they should be required to wear masks.  
https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/covid-19-planning-considerations-return-to-in-person-education-in-schools/

Moderate Dive: Kids and C19 (Summary of the CDC data and guidance)

I. Kids 5 and older can catch it and spread it, just like adults:

In the US through March 2021, the estimated cumulative rates of infections and symptomatic illness in children ages 5-17 years were comparable to infection and symptomatic illness rates in adults ages 18-49 and higher than rates in adults ages 50 and older.  Rates of infection and symptomatic illness in 0-4YOs are roughly half of those in 5-17YOs, but comparable to those in adults 65 and older.  Children and adolescents can spread Scov2 when they are asymptomatic, presymptomatic, mildly symptomatic, moderately symptomatic, or very sick, just like adults. 

II. In-person learning is a good idea.  But it's less of a good idea when community transmission is very high and not a good idea without layered risk mitigation measures:

A study comparing C19 hospitalizations between counties with in-person learning and those without in-person learning found no effect of in-person school on hospitalization rates when baseline county hospitalization rates were low or moderate.  However, this changes when the community transmission rate goes up and significant secondary transmission has occurred in school settings when prevention strategies are not implemented or are not followed.  In Israel, a school was closed less than two weeks after reopening when two students initiated an outbreak of 153 infections among students and 25 among staff members, from among 1,161 students and 151 staff members that were tested.  Importantly, prevention strategies were not adhered to–specifically, they lifted the masking mandate.   The majority of cases that are acquired in the community and are brought into a school setting result in limited spread inside schools when multiple layered prevention strategies are in place and most studies have shown success in limiting transmission in schools have required that staff and students wear masks.  Inconsistent mask use likely contributed to school-based outbreaks.  


III. What about distancing and hand-washing?

Distancing is less important with data showing that 1M separation between kids in school was not a higher risk than 6 feet.  The recommendation to distance 6 feet was based on a (now understood to be false) assumption that Scov2, like colds and flu, spreads by direct and fomite transmission vectors.  Where did the CDC get such an idea?  It wasn't from the C19 data but from data on prior common respiratory infections which commonly are spread through touch and droplets from sneezing and coughing up phlegm.  Because C19 is a dry respiratory disease (that for a year and a half did not manifest with productive cough or runny stuffy nose), transmission has been primarily through virus-containing aerosols (airborne transmission).  My addition: Now, however, with Delta, we are starting to see a new presentation in which C19 in many people looks very much like seasonal allergy or a cold.  This could finally make all of that hand washing and surface sanitizing something more than 'hygiene theater.'  Let's do it all and add every reasonable layer of protection at our disposal.  

916.https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/transmission_k_12_schools.html

 IV.  If kids are highly unlikely to wind up with severe illness from C19, why vaccinate them or make them wear masks?  

917.  One reason is that they, like adults, seem to be getting PCS/long-covid at a fairly high rate.  Difficulty concentrating, problems with memory, and fatigue are among the most common problems and these things have profound consequences for academics and athletics in the near term.  There is as yet no way to know what contracting C19 will mean down the road for children and one could make the case, based on the data so far, that they have the most to lose if the damage (to brain tissue, for example) caused by infections turns out to be permanent.    
https://www.nytimes.com/2021/08/08/health/long-covid-kids.html

918 - 925.  Delta Plus, Lambda (the VOI formerly known as C.37), and B.1.621 

As noted in previous briefings, Delta has shown a pattern of spreading very fast, peaking, and then declining sharply irrespective of vaccination rates.  Time to the peak seems to be about 2 months.  That puts us just about a month away from the peak here in the US.  What comes next?  Likely another brief lull.  And then?  Infections due to Delta dropped suddenly after the peak in India and the UK but never went away.  Now we are seeing Delta rising again in the UK, where they have stopped masking and staying flat at a fairly high rate in India.  My crystal ball says we should probably expect the peak in September, followed by a drop in cases but not to pre-Delta levels, followed by a resurgence if we do not reinstitute universal masking and get significantly more people vaccinated (including boosters for those of us who were vaccinated early).  

Another possibility is that we could see Delta quickly replaced by another new VOC.  Delta Plus is a contender, as it is genotypically the same virus as Delta with one additional mutation in the RBD that is thought to enhance its ability to bind even more tightly to ACE2.  India has declared Delta Plus as its own VOC but the WHO and CDC have not yet done so.  It is not know how prevalent Delta Plus is in the US but it has been estimated to be higher here than anywhere else.  However, such estimates are specious since neither the US nor India are doing widespread genomic sequencing.   

Another candidate is Lambda.  A new study from Japan indicates that a unique 7-amino-acid deletion mutation in the N-terminal domain of Lambda's spike is responsible for evasion from neutralizing antibodies and may make this VOI significantly more resistant to vaccine-induced immunity and natural immunity from prior infections.  These findings mirror those of a study released a few weeks ago from Chile.  According to the GISAID Initiative, there have been 1037 documented cases of Lambda so far in the US.  

According to the WHO, Lambda (formerly designated as C.37) has been identified in over 80% of infections in Peru since April.  The variant was first identified in Peru in August 2020.  The WHO declared the Lambda a VOI (not a VOC) on June 14 because it became a dominant variant in large areas of South America but it has not been established yet whether or not it spread more quickly than the D614G 'wild type' strain, is more virulent, or has significantly better immune evasion.  In January, it made up 1% of the genomically sequenced cases in Lima; by March, it was 50%, and by April, it was 80%.  But its numbers appear to be waning now.  Higher viral titers and better ACE-2 binding capacity are likely factors driving increased transmissibility and this is one way a VOC can outcompete other strains.  But as we move closer to herd immunity, competition might shift toward selecting variants that have more immune escape.  This, of course, is the dreaded outcome.  If Lambda's immune evasion ability is significantly better than that of Delta, we could need an entirely new vaccine and have to start the herculean task of worldwide vaccination all over again.  

A third candidate for the next wave is B.1.621 –a variant first identified in Colombia early this year that has become dominant there but has not yet earned its own Greek letter designation.  The European CDC has listed it as a VOI.  It carries several key mutations, including E484K, N501Y and D614G, that have been linked with increased transmissibility and immune evasion.  Early reports have shown B.1.621 to have seeded in Florida.  Again, because of low levels of genomic sequencing, it is hard to know how prevalent it is there (or elsewhere in the US).  

Leaky vaccines

926.  The concept of leaky vaccines has been around for a while.  Essentially, the idea is that if a vaccine helps the host to not get very sick but does not prevent the host from passing the virus to others, intelligent mutation can occur as a result of the virus being exposed to immune cells and antibodies.  The term 'leaky vaccine' can also be replaced with 'imperfect vaccine' as it is meant to distinguish it from a 'perfect vaccine.'  Perfect vaccines are so-named because they mimic the perfect immunity that humans naturally develop after having certain childhood disease.  When a vaccine works perfectly, as do the childhood vaccines for smallpox, polio, mumps, rubella and measles, it prevents vaccinated individuals from not just from getting sick but also from transmitting the virus to others.  Delta, which emerged because of too low vaccination rates, can now bypass imperfect vaccine-induced immunity at a fairly high rate and vaccinated people (and those with prior infections) can now catch C19, get sick, and pass it on, improving the virus' ability to mutate intelligently to become (evolutionarily) fitter.  This is the first controlled study to validate the leaky vaccine theory, demonstrating how the virus can become more virulent through this process.  But it would probably be more advantageous to Scov2 to improve its fitness by mutating toward better immune evasion and/or transmission.  That's exactly what we're seeing.  
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002198