COVID: asymptomatic people have high viral load

 A recent Korean study found a high rate of people with asymptomatic SARS-CoV-2 (36%), long-term PCR positivity (many over 3 weeks), and similar viral loads to those who were symptomatic (see covid asx korea jamintmed2020 in dropbox, or doi:10.1001/jamainternmed.2020.3862). 

 

Details:

-- 303 symptomatic and asymptomatic patients with SARS-CoV-2 infection between March 6-March 26 who had been isolated in a community treatment center in Korea because they were SARS-CoV-2 positive

-- median age 25, 66% women, 4% had comorbidities (ten had hypertension, one cancer, one asthma)

    -- though not statistically significant (especially given the small numbers), it may be notable that only 2 of the patients who were asymptomatic had comorbidities (whereas 10 of the symptomatic ones did)

-- median time from diagnosis to isolation was 6 days

-- most common symptoms in the symptomatic group were cough (56%), rhinorrhea (46%) and sputum production (30%)

-- repeated PCR tests were done from the upper respiratory tract (nasopharynx and oropharynx swabs) and lower respiratory tract (sputum)

    -- release from the treatment center required negative PCR results and a negative conversion was considered when both upper and lower respiratory tract specimens were negative

-- testing was performed on days 8, 9, 15, and 16 of isolation; further testing was done at physician discretion.

Results:

-- symptom status:

    -- symptomatic: 193 patients (64%) at time of isolation

    -- asymptomatic: 110 patients (36%)

        -- presymptomatic: 21 (19%) of the asymptomatic ones developed symptoms during isolation, median interval of time from detection of SARS-CoV-2 to symptom onset was 15 days (interquartile range: 13-20 days)

-- time to a negative PCR, at day 14 and day 21 from diagnosis:

    -- symptomatic: 30% at day 14 and 70% at day 21 (ie 30% had a positive PCR at day 21)

    -- asymptomatic (including presymptomatic): 34% at day 14, and 75% at day 21 (ie 25% had a positive PCR at day 21)

-- median time from diagnosis to 1^st negative conversion:

    -- symptomatic: 19.5 days

    -- asymptomatic: 17 days

         -- statistically nonsignificant difference, P=0.07

-- PCR Ct values (the inverse of viral load) from lower respiratory tract specimens: decreased more slowly in asymptomatic patients (but only for the PCR targeting the RdRp gene and not either the envelope gene or N gene) and in general the Ct values were quite similar at around 38 (<40 being significant) for all

 

Commentary:

-- a huge outbreak in a religious group in Korea led to massive testing and active contact tracing, and subsequent isolation of both asymptomatic and symptomatic patients in community treatment centers

-- though the study found that asymptomatic people are quite similar to symptomatic ones both in terms of their SARS-CoV2 viral loads and duration of PCR positivity, we do not know with certainty that these asymptomatic patients had viable transmissible virus. 

    --PCR viral loads are important markers of viral persistence and, if esp above a certain threshold, potential transmissibility in many other infectious diseases, such as HIV and Hep C. but are we looking at the correct PCR target with SARS-CoV-2???

    -- It is also certainly conceivable that those who remain asymptomatic have fundamental differences in certain aspects of their immunologic response to the virus, and this conceivably might translate to differences in viral transmissibility even with similar levels of viral detection. It is clear that there have been documented asymptomatic viral transmissions, though it is unclear how often these really occur in the population. For example, the difference in the rate in comorbidities (higher in those with asymptomatic infection), though not statistically significant, does suggest that symptomatic patients may be different.

    -- that being said, this study does raise the huge issue that without widespread SARS-CoV-2 testing, there is the strong potential that asymptomatic infected people will serve as a continuing reservoir for the spread of the virus.

    -- And, without such testing, our chances of eliminating the virus through sporadic social distancing, mask use, and restoration of normal activities (workplace, school, bars, beaches, etc.) will likely be limited, with asymptomatic people being a source of long-term continued viral spreading.

    -- Which also means that this virus is going to be around a long time, unless there is both a safe and effective vaccine available, and a large percentage of people are willing to be vaccinated (helping achieve herd immunity)

-- this study found that the vast majority of people (81%) who were initially asymptomatic remained so during a median of 24 days from diagnosis

-- the length of time that people continue to have a positive PCR was significantly more than the standard 14 day quarantine advocated, with 30% of symptomatic and 25% of asymptomatic patients being positive at day 21. Again, it is not clear that the virus is viable/transmissible for that long. But a real concern...

 

Limitations:

--there are real limitations of PCR testing, and specifically many false negatives (see http://gmodestmedblogs.blogspot.com/2020/05/covid-false-negative-pcr-results-over.html). So, there are likely many asymptomatic patients with SARS-CoV2 who are missed by the PCR testing. Of course, it is not clear what the false negatives in asymptomatic people means. Is it problems with the test? Is it suboptimal PCR targets? Is it the viral load (and perhaps a low viral load may mean less transmissibility)?  But very likely that there will be some transmissible virus from those who screen negative, as has been documented in some cases

--the big issue: how often do people with positive PCRs have viable, transmissible virus?  Would be great to have had viral cultures done in a series such as this one, at least getting us closer to see if the virus was alive and dangerous (though, as mentioned before, cultures are still lab tests and do not necessarily reflect viral viability in real people)

--these were young, healthy people in one site, so that might limit generalizability

 

So, a few take-aways:

--asymptomatic infection seems to be pretty common (also see http://gmodestmedblogs.blogspot.com/2020/07/covid-asymptomatic-infections-in.html, http://gmodestmedblogs.blogspot.com/2020/04/covid-asymptomatic-homeless-patients-in.html,  and http://gmodestmedblogs.blogspot.com/2020/06/covid-seroprevalence-10x-higher-than.html )

--PCR is still positive in many people >21 days after infection. Still unclear how often the virus is transmissible then

--our assumption at this point, i think, should be that asymptomatic people, even those who remain asymptomatic (ie are not just presymptomatic), are a potential source of transmitting SARS-CoV-2. And this should be part of the equation in opening up bars, beaches, workplaces, schools.  

    --This could mean more aggressive testing to include all, not just those with symptoms.

    -- and, having universal precautions (like with HIV of old): assume everyone is positive, keep distance of at least 6 feet and perhaps much more (see http://gmodestmedblogs.blogspot.com/2020/08/covid-transmission-and-distancing.html ), use masks (with the understanding that the virus may hang out in the air for up to 3 hours: so masks should be worn regularly and not just when passing someone on the street), and really reinforcing these issues when at home as well (where those going outside might unwittingly bring back virus, and the virus may hang out for a long time in the stagnant air inside and infect those remaining quarantined at home)

geoff

 

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