A couple of quick hits. I don’t think I mentioned this before, but here is an editorial from the National Academy of Sciences regarding schools being open. They recognize the greater harm that results from not having in-person school. (JAMA Article) You can find the report here–you can buy a paperback, but I believe the full report is also available for download. (NAP Book)
A similar viewpoint is expressed in the prestigious New England Journal of Medicine. (NEJM Article) Here is the quote: “Until these children physically return to school full time, many will lose out on essential educational, social and developmental benefits; neither the economy nor the health care system will be able to return to full strength given parents’ caretaking responsibilities; and profound racial and socioeconomic injustices will be further exacerbated.” The article summarizes everything we have said about children’s low risk, low role in transmission and the pathetically inadequate nature of in-person schooling.
This quick note from the NEJM deals again with the Diamond Princess ship and specifically the 96 asymptomatic cases who were transferred to a hospital in Japan upon docking. Only 11 of these people eventually developed symptoms. The risk of becoming symptomatic increased with age, as did time to clear infection. Most of these 96 people had tests with cycle numbers above 30. The median time to developing symptoms was 4 days after the first PCR test. (NEJM Article)
This is another study comparing saliva tests versus nasal swabs for PCR testing. (NEJM Article) Using 70 inpatients, specimens collected by each method over time were tested. Saliva generally had more RNA copies. There was more variation in RNA levels in nasal specimens. A higher percentage of the saliva samples were positive up to 10 days after diagnosis. They also tested 495 asymptomatic health care workers and found that 13 were positive by saliva compared to 9 by nasal swab. Oh great, just what we need, more low positives. Looking at the supplementary material, we see that a threshold of 38 cycles was used, so high. The inpatients were infected, so as you would expect, for both saliva and nasal swabs, there were relatively low cycle numbers. But among the health care workers, the saliva consistently picked up more virus. For the nasal swabs, a large number were above cycle number of 30. Given the apparently superior and more sensitive performance of saliva, you should be able to use a lower cycle number for that test.
Here are a couple of studies relating to develop of immune response across coronaviruses. The first is yet another paper attempting to identify parts of all the coronavirus strains that are very similar. The authors were doing this to aid in development of a vaccine that could be effective against all strains and future variations. (Medrxiv Paper) They found a number of such regions and found that they appeared to prompt B and T cell responses. Altogether 24 regions or epitopes were found that were highly conserved across CV genomes and that prompted human immune system recognition. From this 16 were identified by further testing as having the highest potential for cross-reactivity and recognition. These regions prompted immune responses from the healthy donors as well as the CV-19 patients, although the pattern differed. Most importantly, they found that memory T cell responses to certain of these common CV regions existed in the healthy donors. A similar finding occurred in regard to B cells. This included some reactivity to regions in the spike protein. Comparing memory of these various cell types with severity of illness, asymptomatic patients had higher levels of memory T cell responses. Maybe Dr. Fauci should read this paper and he would understand what Rand Paul was talking about.
This paper similarly looked at responses to CV-19 genome regions among about 230 patients and 190 people sampled before the epidemic. (Science Article) This paper looked solely at B cell or antibody response. It also found some pre-existing response to one portion of the CV-19 genome. The CV-19 samples included in the study also showed higher antibody reactivity to the first SARS coronavirus, MERS and seasonal CV. The authors identified one particular region that seemed highly cross-reactive in pre-CV-19 donors, near the fusion protein (which aids in penetrating the membrane of a targeted cell). Another interesting general finding was that among hospitalized CV-19 patients there was a generally weaker antibody response to common respiratory viruses.
And finally, as we have suspected, antibody surveys are probably missing a lot of people because of too high a threshold for detection. (Medrxiv Paper) The study comes from Canada and the authors found that lowering the threshold by half increased detection by 16%.