COVID: subsequent positive PCR tests are probably not important

A Korean CDC press release on May 19 analyzed 447 Covid-19 cases that were re-positive (i.e. the PCR went from positive, to negative, then back to positive: a finding in several other but much smaller studies), see https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030&act=view&list_no=367267&nPage=1

 

Details:

-- the Korean CDC, having found many cases of people going from positive to negative PCR and being discharged from isolation, but then turning PCR positive, decided to assess the communicability of SARS-CoV-2 in this group; they had been managing these cases as if they were newly confirmed Covid-19 cases

-- in 3 areas of Korea reporting, between 26% and 49% of the cases tested positive again after negative tests (ie, re-positivity is quite common)

-- 447 re-positive cases were identified; epidemiologic and contact investigation were completed for 285 of them

    -- for these 285 re-positive cases, 790  contacts were identified (351 family members, 439 others)

    -- reasons for retesting:  107 patients (38%) for symptoms (not defined); 170 patients (60%) just for this investigation

    -- but on further questioning: 126 (45%) actually had symptoms present

Results:

-- for 226 patients,  it took 45 days (8-82 days) from initial symptom to testing positive again after discharge from isolation, with a bell-shaped curve; and 14 days (1-37 days) from discharge to a positive test

-- in all re-positive cases and newly confirmed ones, neutralizing antibody was found from the first serum!!! 

-- Of 108 re-positive cases: all had negative viral cell cultures

    --of these 108 patients: 67% female, 10-20% in each 10-year age group from 20-69, symptoms present in 48%, Ct value on PCR: above 30 in 90%

    -- of the 23 who had second serum samples, 96% had neutralizing antibodies

    -- another respiratory virus was also found in 3 of these 108 patients

-- of the 790 contacts tested: a minimum of 14-day monitoring found:

    -- 27 contacts were positive, but 24 had been previously confirmed Covid-19 infection

    -- 3 newly confirmed cases: all had history of contact with the Shincheonji religious group or a confirmed case in their family; viral cultures were negative in 2 of them (3^rd had only indeterminate PCR and they were not able to do a viral culture)

Commentary:

--pretty impressive study suggesting that those having PCR testing after recovery (and a negative interim test) did not have any transmissible virus.

    --it is still not clear from this study that people remaining and continuing to be positive after 14 days or so would have the same findings.

    --but, per the US CDC, replication-competent virus has not been successfully cultured more than 9 days after illness onest, though the PCR can be positive for 6 weeks. this was based on an analysis of several small studies. see http://gmodestmedblogs.blogspot.com/2020/05/covid-updated-cdc-guidelines-for.html

-- it would have been interesting to have a comparative group of patients who remained PCR negative: eg, 45% of those who were re-positive had symptoms. Is that different from those who remained negative??? (we are certainly seeing lots of patients who continue to have symptoms, esp cough and fatigue, weeks after their discharge from the hospital or the home isolation period was completed)

-- it was notable that neutralizing antibodies were found in the first serums of all of the re-positive cases, suggesting pretty strongly that they were not reinfected (though we do not know the titers), and they all also had negative viral cultures [the best guess is that neutralizing antibody is probably the effective one in developing SARS-CoV-2 immunity, based on studies with other viruses; and having neutralizing antibodies is required in convaslescent plasma for it to be transfused from former Covid-19 patients into very sick new cases: see http://gmodestmedblogs.blogspot.com/2020/04/covid-convalescent-plasma-seems-to-help.html . Not all patients with Covid-19, however, develop detectable neutralizing antibodies, perhaps allowing for their being reinfected in the future. Thanks to Anna Wald for making the point that we do not have actual data on the protective effect of neutralizing antibodies with SARS-CoV-2]

-- another useful finding was that the neutralizing antibodies remained positive in second samples of re-positive patients. ie, they seem to last at least awhile

As a result of this study,

-- the Koreans modified their algorithm. they decided that:

    --there was no need for 14 day self-isolation after discharge from formal isolation

    --there was no need for PCR testing if symptoms appear within 14  days of discharge [though there might be cases of reinfection, as suggested below]

    --there was no need to manage re-positives similar to confirmed cases (isolation)

    --there was no need to manage contacts similar to they way they had managed contacts of confirmed cases (quarantine), though they do suggest investigation of contacts of re-positive cases

-- they decided to change the terminology from “re-positive cases” to “ PCR re-detected after discharge from isolation”

some relevant prior blogs:

--the rate of false negative PCRs is very high in the first week, lowest around 5-7 days after exposure, then increases. BUT, there are many documented cases of going from 2 negative PCRs to a positive one later. see http://gmodestmedblogs.blogspot.com/2020/05/covid-false-negative-pcr-results-over.html

--there may also be reinfection, as suggested but not definitive in http://gmodestmedblogs.blogspot.com/2020/05/covid-reinfection-cases-and-risk.html

--for determining infection, the PCR test is the best test in first 8 days, then Ab is better for determining infection later http://gmodestmedblogs.blogspot.com/2020/04/covid-antibody-testing-and-concerns.html 

  

so, a pretty powerful reasonably large study, which basically found that re-positive patients are pretty common, and had no culturable virus. And there was no evidence of viral infection, both from testing the patients or their contacts, which suggests:

--no need to do PCR testing at the end of an infection.  This is reinforced since the CDC in their review found no culturable virus 9 days after the onset of illness

--and perhaps no need for prolonged isolation after maybe 14 days from onset of illness (to give a cushion, since the 9 days is based  on small studies and really should be replicated)

geoff

 

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