COVID: asymptomatic infections, and ???viral persistence

2 recent articles suggest that asymptomatic SARS-CoV-2 infection is quite common

-------------------------------------

In a replication of the Shakleton Antarctic exploration, a cruise ship meandered through his excursion route, this time hampered by rampant SARS-CoV-2 infection (though i believe that Shakleton was not exactly on a cruise ship.  interesting that both adventures did not go exactly as planned...). but the scientific plus of this SARS-CoV-2 study is that all passengers and crew members were tested by PCR for the virus, so it is a study of an all-inclusive group (see covid asx carrier ship thorax2020 in dropbox or doi:10.1136/thoraxjnl-2020-215091)

Details:

--217 passengers and crew on a cruise ship, 128 (59%) tested positive for SARS-CoV-2: 128 passengers and 95 crew

--the trip started in Argentina for a 21-day excursion of the Antarctic Peninsua, departing mid-March

--all pateints and crew were screened for Covid-19 symptoms and body temperatures prior to boarding. and none had been through high Covid-19 hotspots (eg China, Macau, Hong Kong, Taiwan, Japan, South Korea or Iran) in prior 3 weeks

--there were multiple hand hygiene stations onboard

--all passengers and crew had regular body temperature reviews

--on day 3 of the trip, the cruise course was altered because of travel restrictions, abandoning South Georgia island

--on day 8: first recorded fever in a passenger, leading to isolation protocols, passengers being confined to cabins, full PPE for those having contact with febrile patients, and N95 masks by all with contact with anyone in their cabins (meals were delivered 3/d to cabins, and cabins were not cleaned)

--on day 10: fevers in 3 crew; day 11 in 2 passengers and 1 crew; day 12 in 3 passengers; 3 more on day 14

--8 people were medically evacuated to a hosptial in Uruguay for impending respiratory failure, including one of the 2 ship physicians

--on day 20 all passengers and crew had SARS-CoV-2 testing done

--from departure in mid-March and for next 28 days, the ship had no outside human contact and remained in a totally isolated environment

Results:

--24 (19%) of the 128 people were symptomatic

--8 (6%) required medical attention

--4 (3%) were intubated and ventilated

--1 (0.8%) died

--and, 104 (81%) were asymptomatic

Commentary:

--this study was remarkable by its thoroughness. it is not explicitly stated, but it seems that they followed the asymptomatic people long enough to see if they became symptomatic (the typical incubation period is about 5 days)

--these numbers of asymptomatic patients is staggering. and, as we know:

    --people have transmissible SARS-CoV-2 in the asymptomatic state

    --there are clearly specific characteristics of cruise ships that lend to higher transmission rates (close quarters, high levels of contact, social anti-distancing), and this huge reservoir of positive asymptomatic people could well be a reservoir for the continuing SARS-CoV-2 infections on the ship

    --however, we do not know specifically if those who remain asymptomatic (vs those who are just presymptomatic) transmit the virus as regularly as symptomatic people, or for how long their virus is transmissible (though see next article)

--they did rapid SARS-CoV-2 testing  on the the initial 6 febrile patients and all were negative, suggesting the unreliability of their rapid test (and confirming other studies finding high rates of false-negatives: http://gmodestmedblogs.blogspot.com/2020/05/covid-false-negative-pcr-results-over.html )

--the Diamond Princess cruise ship reported very early in the pandemic that 18% of those getting SARS-CoV-2 remained asymptomatic: see https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.10.2000180

--so, one inescapable conclusion: cruise ships should be avoided.....   and, as a corollary to that, probably not a great idea to make large investments in the stock of cruise ship companies

------------------------------------------------------------------------------

A Chinese study from Wuhan compared the clinical characteristics of people with asymptomatic vs symptomatic SARS-CoV-2 (see covid asx china jama2020 in dropbox, or doi:10.1001/jamanetworkopen.2020.10182)

Details:

--all consecutive hospitalized pateints with confirmed Covid-19 were enrolled

--they were from 26 clusters with confimred history of exposure to the Hunan seafood market or had close contact with another patient who had been hospitalized for Covid-19; they were all confirmed to have SARS-CoV-2 infection by PCR, from 12/24/19 to 2/24/2000

--78 close contacts were identified from the 26 clusters, all with confirmed SARS-CoV-2. and all were hospitalized and monitored for symptoms daily

    --close contacts with other potential exposure history were excluded

    --routine chest CT and nasopharyngeal swabs for SARS-CoV-2 were done on these close contacts

    --a second chest CT was done 4-6 days later, then 6-7 days after the second one. more often if clinically indicated

--the date of the initial exposure was recorded to determine the incubation period

Results:

--33 patients (42%) were asymptomatic and 45 (58%) symptomatic

--asymptomatic patients were:

    --younger: 37 vs 56 yo

    --more often women: 67% vs 31%

    --less liver injuries (increased ALT or AST): 13% vs 20%

    --higher CD4 count: 719 vs 474

    --faster lung recovery on CT: 9 vs 15 days

    --shorter viral shedding per nasopharyngel swab: PCR 8 vs 19 days

    --more stable PCR testing: fluctuating results in 12% vs 33%

Commentary:

--and, another study finding a pretty high rate of asymptomatic patients.

--the higher CD4 counts in asymptomatics suggests less immune injury (SARS-CoV-2 can infect T cells: see http://gmodestmedblogs.blogspot.com/2020/04/covid-new-nih-guidelines-t-cells-having.html )

    --for example, in Wuhan, of 452 patients with Covid-19, those with more severe disease had higher inflammatory cytokines (TNF-a, IL-6, etc) and lower helper T-cells (CD3+ CD4+) of 285 in severe vs 421 in nonsevere Covid-19 (normal 550-1440): see covid  T cells lower CID2020 in dropbox, or DOI: 10.1093/cid/ciaa248 

    --though, there was a rather disturbing article recently in the basic science literature suggesting that SARS-CoV-2 (but not SARS-CoV, the virus causing SARS 20 years ago) is associated with target cell membrane changes that may limit cytotoxic T-lymphocyte (CTL) responses: this decreased CTL elimination of the virus could be by downregulating  MHC-1 (major histocompatability complex class 1 molecule) expression on cell surfaces, decreasing antigen presentation, and potentially reducing recognition of virus-infected cells.

         --and this could have profound effects on viral persistence, future immunity, or vaccine efficacy. As also happens with HIV, which has a similar effect on MHC expression, as reported in https://www.scmp.com/news/china/science/article/3086177/coronavirus-uses-same-strategy-hiv-dodge-immune-response-chinese , and in the pre-publication article: https://www.biorxiv.org/content/10.1101/2020.05.24.111823v1.full.pdf . Also,some herpes viruses similarly can suppress MHC expression, and may be a factor in their becoming chronic infections. though at this point we do not have evidence of chronic SARS-CoV-2 infection as with these other infections. 

        --and, does this ???prolonged viral persistence have any relationship to the fact that the PCR for SARS-CoV-2 can remain at high titer for up to months after the virus seems to be nontransmissible??  is there a place that the virus is lurking but dormant (and nonculturable in the blood or other sites assessed) that is stimulating the "viral load" picked up by PCR, with the potential for virus to re-emerge?? perhaps over time, or if anything disrupts the individual's immune function? and are these dormant sites inaccessible for decisive therapy or potentially for vaccine effectiveness???  there seem to me to be several unsavorable possibilities...

so,

--good news that these asymptomatic patients seemed to shed the virus for less time than symptomatics (ie, it does not seem that they are continually shedding the virus, one reasonable concern), though they were checking PCRs, which do seem to be increasingly unreliable over time (http://gmodestmedblogs.blogspot.com/search?q=covid+false+negative%5C ). would be great to have further studies using viral cultures as well as PCR

--but, again, these asymptomatic patients can have transmissible virus, which really becomes a concern since asymptomatic SARS-CoV-2 seems to be relatively common, and the viral vectors (asymptomatic people), who typically do not realize they have the virus, are less likely to take the aggressive isolation methods needed to prevent transmission, and may well sustain a continuing viral pool spreading Covid-19 in the community...

geoff

 

If you would like to be on the regular email list for upcoming blogs, please contact me at gmodest@uphams.org

 

to get access to all of the blogs:

1. go to http://gmodestmedblogs.blogspot.com/ to see them in reverse chronological order

2. click on 3 parallel lines top left, if you want to see blogs by category, then click on "labels" and choose a category​

3. or you can just click on the magnifying glass on top right, then  type in a name in the search box and get all the blogs with that name in them

 

please feel free to circulate this to others. also, if you send me their emails, i can add them to the list