25 Sept COVIDology 74 Immmunology and vaccine politics

Dear colleagues,

Happy to be back home. We just escaped Switzerland and France, before the “red zone” hits it.

1. The news of the day: type 1 interferon antibodies in more than 10 % of seriously ill patients with almost all men (X-linked trait) and half over 65.  In addition, 3.5 % of critically ill COVID  patients harbored mutations in 8 of the interferon 1 genes.  The as-yet unexplained aspect is why these patients apparently had not been particularly prone to serious complications of other viral infections (including flu). In attachment the editorial comment. I could not yet find the full papers.    

2. A very intriguing study by Pierce et al compares immune responses in pediatric and adult patients in a COVID ward in New York.  As expected, the young patients had a better outcome, but remarkably both antibody (neutralizing and phagocytosis-inducing) as wezll as T cell responses against spike were higher in adults.  Also there was no difference in pre-existing antibodies to other coronaviruses according to age or outcome.  The authors point to serum levels of IFN-g and IL-17A as potentially important markers, because they were higher in younger patients and those with lower neutralizing antibodies, but when one looks at Fig 2 p. 10, it is evident that those cytokines, like many others are highest in the most severe groups of patients. Unfortunately, no data on type 1 interferon

Taken together also with previous literature, it becomes evident that the innate, rather than adaptive immune responses are important to protect against severe disease. There is as yet also no convincing evidence that memory responses due to cross-reactivity with previous common coronaviruses has an important role in pathogenesis or protection.  These observations, of course, do not mean that inducing specific B and T cell immunity by vaccination would not protect against infection.   

3. After having taken a short holiday, I come back in a country, where the underlying logic of the policy on COVID prevention is difficult to follow.   It can be worse, as is shown in this article of the NYT: apparently the CDC first warned against airborne transmission, but then retracted the statement on the same day….  https://www.nytimes.com/2020/09/21/health/coronavirus-cdc-aerosols.html?utm_source=Nature+Briefing&utm_campaign=5a4e4d6162-briefing-dy-20200922&utm_medium=email&utm_term=0_c9dfd39373-5a4e4d6162-44799709 . 

4. Manaus in Brazil seems to offer a view on the death toll of herd immunity.  Despite some measures taken COVID spread very widely in this 2 million people city.  The preprint in medRxiv suggests that in total up to 66 % of the population has been infected, before the infection waned.  This was based on serology (antibody) studies).  The total death toll was over 3.000 (Fig S5 p. 25).  The overall infection fatality rate was estimated at about 0.225% (p. 8). (I failed to find the number of confirmed infections, hence could not calculate the case fatality rate).   The fatality rate was mitigated by the (young) population structure (Fig S1A p. 21), since the age-adjusted infection fatality rate increased to  about 6 % in the 80+ group   (Fig S1B).

5. Two papers on the politics of vaccine:

• A UK initiative to challenge young volunteers

My question: how could you defend this trial ethically in the absence of specific curative treatment?

• How WHO envisions to distribute vaccines through COVAX:

WHO’s “fair allocation mechanism” proposes distributing vaccine in two phases. In the first phase, all countries would receive vaccine proportional to their population; initially enough vaccine to immunize 3% of their population, with the first doses going to frontline workers in health care and social care. Then, additional vaccine would be delivered until 20% of a nation’s population is covered. WHO envisages that these doses would be used to immunize those at the highest risk from COVID-19: elderly people and those with comorbidities.

In the second phase, vaccine to cover additional people would be delivered to countries based on how urgently immunizations are needed. The framework suggests two criteria should be used to decide priority:

• how fast the virus is spreading (the effective reproduction number) and whether other pathogens such as influenza or measles are spreading at the same time; and
• how vulnerable a country’s health system is, based on metrics such as the occupancy of beds in hospitals and intensive care units