Drowning in Coronavirus Research, Part 84

A number of you have asked for more explanation about PCR testing.  Some readers have given some good explanations in the comment section.  I am torn between being too technical and not being clear, and there are limits to my own technical understanding.  Here is a pretty good explanation of the basics of PCR testing.  (PCR Article)   While it refers to copying a gene, you can design a PCR test to target any sequence of DNA or RNA or even proteins.  When you are testing a sample to see if it has certain DNA or in the case of a virus, RNA, the formula for crossing a threshhold for a positive result would take into account the number of primer pieces you started with and the number of cycles it took for you to reach the threshhold.  The current controversy around PCR testing, and you may have seen that now large numbers of false positives are being found in college athlete or student testing, is that if the number of cycles to cross the threshhold is very high, it indicates a very low amount of virus, and there is a much higher likelihood of a false positive.  There also is a separate issue with “human error” with the tests, in terms of how the sample is obtained, potential contamination and other problems.  Nothing conspiratorial either way about this, in fact it is quite common for there to be issues with many diagnostic tests.

This paper raises the question of whether antibody prevalence tests are up to the job of identifying people who have been infected.  (BMJ Article)   Issues include the fact that antibody testing alone doesn’t capture the full adaptive immune response–research shows that many people with low antibody levels have strong T cell responses; use of assays that only target antibodies to limited regions of the virus; assays that are capable of detecting low levels of antibodies; and looking for the wrong types of antibodies, especially not looking for those present in mucosal tissues.

This study examined issues around understanding timing of transmission of disease, particularly by those individuals who are non-symptomatic.  (Medrxiv Paper)   The incubation period, or time from infection to symptoms, was estimated at an average of 5.7 days.  The time from the development of symptoms in an index case to development of symptoms in a second person they infected was an average of 4 to 5 days.  The time from infection in an index case to infection in the secondary case was estimated at 5.5 days.  Time from symptoms in the index case to transmission to a secondary case, which is the hardest to determine, was estimated at less than a day.  Transmission was said to be centered around and peak at the day of symptom onset in a primary case, with any transmission likely limited to 5 days before and after symptom onset.  Presymptomatic transmission was estimated to be  40% of all transmissions.  Not clear if this includes asymptomatic people, or if the authors thought they were a limited source of any transmission.  They noted that there is substantial uncertainty in what it takes to be “infectious”.  A person’s likelihood of transmitting is also influenced by behavior changes–a person who thinks they may be sick will probably limit contacts.  My inference is that if transmission peaks at symptom development and you never have symptoms, you aren’t going to be responsible for many secondary cases.

Yet another piece of research on the immune response in patients.  (Medrxiv Paper)   From China, the researchers examined the adaptive immune response from 10 asymptomatic patients and 49 patients with mild, moderate or severe disease.  In general the response was quite different.  For asymptomatics, antibody and related B cell development was quite low, but there was a very vigorous T cell response.  Those with more serious illness had a strong antibody and B cell response, but a limited virus specific helper and killer T cell development.  This has implications for surveys to determine infection levels and potentially vaccine development.

At least in Minnesota, the new hot bugaboo used by the state for terrorization purposes is the threat of long-term health consequences to people who are infected.  First of all, this could only be an issue for people with severe disease, which is an increasingly small percentage of all infections.  Secondly, given how long the epidemic has been going on for, what is meant by long-term?  This study finds that after two to three months most supposedly long-term lung and heart complications from the disease are in fact resolving.  (EA Study)   86 patients were studied for an extended period.  All had severe disease and almost all had serious pre-existing conditions.  Half were smokers.  These long-term effects are no different than those suffered by some flu patients, for example.  And they are clearly rare.

This article further discusses the issue of long-term damage from CV-19.   (LS Article)

This article suggests that the severe damage in CV-19 disease may be related to an inflammatory biochemical pathway called the kinin system.  (BK Article)   (BK Study)   Aside from giving us a better understanding of the mechanisms of the disease, this may mean that certain existing drugs that target the pathway could ameliorate symptoms and effects.