COVID: updated CDC guidelines for isolation of covid-positive

The CDC just released a new document on discontinuing isolation for persons with Covid -19  (see https://www.cdc.gov/coronavirus/2019-ncov/community/strategy-discontinue-isolation.html ).  [some of my comments embedded in their points in square brackets]

Formal recommendation: for persons recovering from Covid-19 illness, they should remain in isolation for at least 10 days [was 7 days] after illness onset and at least 3 days after recovery, defined as resolution of fever without the use of fever-reducing medications and with progressive improvement or resolution of other symptoms [of note, they do not mention cough or shortness of breath specifically as in prior documents or the ones noted below, making it a little unclear what symptoms they are talking about: for example, many patients seem to have persistent fatigue for several weeks; does this remarkably common symptom need to show progressive improvement or resolution??]

-- They also do recommend a test-based strategy if feasible (i.e. 2 PCR tests that are negative and done at least 24 hours apart) or a symptom-based strategy with more stringent requirements [though not defined by them] when there is a low tolerance towards continued viral shedding: e.g. in people who pose a risk of transmitting infection to vulnerable individuals, people residing in congregant living facilities (e.g. correctional detention facilities, retirement communities, ships), and people who are immunocompromised who might have prolonged viral shedding

Details:

-- PCR-measured viral load in upper respiratory symptoms declines after the onset of illness

-- at this time, replication-competent virus has not been successfully cultured more than 9 days after illness onset [of note, they quote several studies, all of which are really small, including the Munich study: see covid munich early virol assessment Nature2020 in dropbox , or https://doi.org/10.1038/s41586-020-2196-x], or prior blog http://gmodestmedblogs.blogspot.com/2020/03/covid-19-update-31120.html , as well as a nursing home study (see http://gmodestmedblogs.blogspot.com/2020/04/covid-presymptomatic-transmission-in.html ) which found viable virus on tissue culture independent of having symptoms (typical or atypical). also, my oft-repeated caveat that viability in a tissue culture may not reflect viability in the human body]

-- also, as per the Munich study, as the likelihood of isolating replication-competent virus decreases, anti-SARS-CoV-2 IgM and IgG can be detected in increasing number of persons recovering from infection [though we do not have documentation that these antibodies are protective]

-- they cite unpublished data finding that attempts to culture virus from upper respiratory specimens have been largely unsuccessful when the PCR is in the low but detectable ranges [it would be great to actually see this data]

-- in general, following recovery from clinical illness, many patients no longer have detectable PCR in their upper respiratory specimens, and those with detectable RNA by PCR 3 days after recovery are generally in the range at which replication-competent virus has not been readily isolated [again, would be great to see this unpublished data]

-- no clear correlation between the length of illness and duration of post-recovery shedding of detectable viral RNA in upper respiratory symptoms [though there have been data suggesting that those with more severe infections are more likely to have higher neutralizing antibody levels, which might be quite important]

-- infectious virus is not been cultured from urine or reliably cultured from feces in several studies

Commentary:

-- it is important to note that the above recommendations are based on a few studies with very small numbers of patients, as well as unpublished data with unknown numbers of people or study quality

-- one Chinese study of 56 patients found that the PCR can be positive for up to 6 weeks after infection; the CDC does note that “it remains unknown whether these PCR positive samples represent the presence of infectious virus”, a comment which does belie the strength of their recommendations above [ie, we really don't have the data we need for strong recommendations: the CDC is trying to make their best guess here based on very limited data. and their recommendations, though strong and reasonably clear, are filled with caveats in the text itself such as this one]

    -- and, very small studies have suggested that viral culture is negative after 8 to 10 days [again, I would be hesitant to extrapolate too much from these very small studies, and the presence of positive PCR six weeks later is quite concerning; PCR can remain positive when there is nonviable virus, but it seems a stretch to me to say that nonviable viral fragments would be detectable 4½ weeks after that 10-day interval when purported viability “approaches zero”, per the CDC]

-- they do appropriately note that the virus is most transmissible very early in the infection, a very important point in terms of our testing and contact tracing (see http://gmodestmedblogs.blogspot.com/2020/04/covid-superiority-of-contact-tracing.html )

-- this recommendation does increase the recommended isolation from 7 to 10 days, based on the small studies above.

-- And, they do note that in situations where there is an especially low tolerance for post-recovery SARS-CoV-2 transmission, that employers or local public health authorities may choose a more stringent recommendation  [not specified, but seems reasonable to leave it to public health authorities. but employers?? do they all really understand the clinical studies??]. And that “no policy decision will result in 100% certainty that all recovered individuals are no longer infectious”

-- they also do have the contradictory caveat that “Ct values (ie PCR viral loads) should not be used to define infectiousness or to demonstrate the absence of risk for transmission” (which does seem contradict their recommendation of having 2 negative PCR tests in those who are at high risk or healthcare workers, though a couple of negative PCRs probably does decrease the likelihood of transmission. but there are several cases of people having even 2 negative PCRs and then having a positive one...)

So, I do think that at this time it is appropriate to extend the 7 to 10 day isolation post-infection. I am still somewhat concerned about the possibility of continued viral transmission, pending larger studies. My approach at this point is to suggest to people that after the 10-day period, they should be particularly aggressive in continuing isolation to the extent they can for the next 2 weeks

    -- with at least increased social distancing

    -- wearing a mask at home to decrease their touching their nose or mouth and potentially spreading virus onto surfaces (which another person could then touch)

    -- and frequent handwashing

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This document also has links to other current documents:

 For ending home isolation for immunocompromised patients https://www.cdc.gov/coronavirus/2019-ncov/hcp/ending-isolation.html )

-- they recommend home isolation until resolution of fever without the use of fever-reducing medications, and improvement in respiratory symptoms (e.g. cough and shortness of breath), and 2 consecutive upper respiratory swab specimens collected at least 24 hours apart (though this test-based strategy is optional, and one could follow the symptom-based strategy as below)

Criteria for return to work for healthcare personnel with suspected or confirmed Covid-19 (see https://www.cdc.gov/coronavirus/2019-ncov/hcp/return-to-work.html 0

-- they recommend exclusion to work based on:

    -- symptom-based strategy: at least 3 days have passed since recovery, defined as resolution of fever without the use of fever-reducing medications and improvement in respiratory symptoms (e.g. cough and shortness of breath) and at least 10 days of past since symptoms 1^st appeared

    -- test-based strategy: resolution of fever without the use of fever-reducing medications and improvement in respiratory symptoms (e.g. cough, shortness of breath) and negative results of FDA Emergency Use Authorized Covid 19 assay for detecting SARS-CoV-2 from at least 2 consecutive respiratory specimens collected at least 24 hours apart

-- and for healthcare workers with laboratory confirmed Covid-19 but no symptoms:

    -- 10 days have passed since the date of their positive Covid diagnostic test, assuming they have not developed symptoms (if symptoms develop, you can use either of the above 2 strategies)

    -- or test-based strategy of at least 2 consecutive negative respiratory specimens collected at least 24 hours apart

    -- There is a strong caveat here that it is possible that viral shedding could be longer or shorter than the 10 days after 1^st positive test, and individuals with asymptomatic infection may have prolonged detectable RNA [there are very limited data on this]

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BUT, THE REALLY GOOD NEWS:  the White House has decided that it is now time to phase out the coronavirus task force (see https://www.nytimes.com/2020/05/05/us/politics/coronavirus-task-force-trump.html?referringSource=articleShare  ), with our public health guru vice president Pence noting "it really is all a reflection of the tremendous progress we've made as a country". i just wish he specified which country. and our other public-health guru, Jared Kushner, will oversee the development of the vaccine.....

geoff

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