COVID: WHO: don't trust antibody testing

The World Health Organization (WHO) assessed the data on immunity post-Covid-12 infection, suggesting that there was “no evidence that people who have recovered from Covid-19 and have antibodies are protected from a second infection” (see https://www.who.int/news-room/commentaries/detail/immunity-passports-in-the-context-of-covid-19 ), countering the claims by some governments that those with antibodies could serve as an “immunity passport” or “risk-free certificate” and return undaunted into the workforce, etc.

Details:

--most who recover from infection do have antibodies

--immunity develops over 1-2 weeks after infection

--BUT, some have very low levels of neutralizing antibodies (in those people, perhaps cellular immunity may be necessary to recover)

--there are no data finding that immunity from prior infection does protect people from subsequent infections

--and the rapid immunogdiagnostic tests need further validation to determine their accuracy and reliability: and there are potentially major consequences if the test is either falsely positive or negative, and that leads to changes in the individual’s behavior

--any antibodies need to be specific to SARS-CoV-2 and not detect antibodies to the 4 common coronaviruses that occur annually and cause simple URIs, or the other 2 known bad ones: SARS-CoV and MERS-CoV

--this is not to say that studies should not be done with these antibodies: they might provide useful information. Just that we should not assume that antibodies confer protection at this point

Commentary:

--despite the current vilification of the WHO by he-who-should-not-be-named, this advisory to me is “spot-on” [this is the same individual who likes to blame others for problems (like non-white immigrants; or in the Covid-19 case, the Chinese)]

--studies have suggested that antibodies do regularly form, with IgG and IgM  detectable in about 80-90% of people around day 16 of infection, then IgG decreasing to detectable in about 70% by day 21 and IgM in the 70-90% range. But antibodies do not occur after all infections: see http://gmodestmedblogs.blogspot.com/2020/04/covid-antibody-testing-and-concerns.html

--this same blog looked at the horribleness of the current antibody tests: Spain found 30% sensitivity, a UK study found 0%. And the fact is that of the >90 tests around, the FDA allows only 4 now.  these were not independently verified: these were validated by the manufacturer but allowed onto the market without formal FDA approval. The FDA utilized the Emergency Use Authorization, intended for use by clinical labs, to authorize the ones they did (see https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-serological-tests ; and https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd)

--and there are really important unknowns:

     --it is likely that the protective antibodies are the neutralizing ones, which appear moreso in those with more severe infections, are more likely to be effective if there is a titer of 1:1024 or higher, and may not be detected at all in some patients (esp in those with milder infections).  In a plasma transfusion study, they required this titer in order to harvest the plasma to give to sick patients (see http://gmodestmedblogs.blogspot.com/2020/04/covid-convalescent-plasma-seems-to-help.html ).  there is no info about neutralizing antibodies in those with asymptomatic infections

    --so far, so good that the genetic variability of the SARS-CoV-2 seems to be minor.  A major change would be disasterous: conceivably even an effective vaccine for our current virus could be less effective with a major genetic shift. or drugs that finally do work might not in the future. [similar to the influenza genetic shifts]

--there are several cases of people going from a positive PCR to negative on a few tests, then to positive. What is happening here? Is there a new infection? Do they have transmissible virus the second time around? Were there false negatives causing the negative tests ( in a Chinese study they confirmed the subsequent positive ones with a different testing kit)

So, there are just so, so many unknowns.  But the bottom line is that there are real concerns about:

-- the quality of the tests (esp the antibody ones)

-- the interpretation of tests: PCR can remain positive for some time after the virus is dead (it assesses viral fragments, not whether the virus is viable). And even viral tissue cultures, though very suggestive of the viability of virus in infecting humans, is still a bit of a leap of faith to assume growth in humans

-- whether we are looking at the right antibodies: the IgG may not be protective. it seems likely to be the neutralizing antibody that matters, and it does not have a clear relationship with IgG. and even neutralizing antibodies are present, there may not be  sufficient titers to matter. and there are no readily available tests that measure the titers of neutralizing antibodies: only IgG, IgM, and both

—and, whether any of these antibodies mean anything when actually tested in humans

But the bottom line, as articulated by WHO: do not assume that if one has antibodies (IgG/IgM), even if there were a really good test,  that they are necessarily protected. The role of antibody testing now is exploratory and needs good studies to see even which ones are useful predictors of immunity

geoff

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