COVID: presymptomatic transmission in nursing home; test EARLY

Another study reinforced the urgency of testing people for SARS-CoV-2 in the asymptomatic or early symptomatic period: a detailed study of SARS-C0V-2 transmission in a skilled nursing facility in Washington state (see covid asx transmission nurs home nejm2020 in dropbox, or DOI: 10.1056/NEJMoa2008457)

Details:

-- this was the 2^nd nursing home affected by SARS-CoV-2 in King County, Washington: a skilled nursing facility with 116 beds

-- nursing staff assessed nursing home residents (NHRs) twice daily for possible signs and symptoms of Covid-19, including oral temperatures and screening for cough, shortness of breath, sore throat, or any other respiratory symptom. Healthcare personnel were also assessed for these at the beginning of each shift.

-- March 1, one day after this intervention started, one healthcare worker was positive while working in a unit of the nursing home while symptomatic 3 days previously.

-- March 5, the facility was informed that one of their residents were hospitalized with Covid-19; on March 6 all visitors were restricted and communal activities canceled. all healthcare staff entering symptomatic residence rooms used extensive PPE’s

Results:

-- of the 89 nursing home residents (NHRs ) in the facility where the 1^st NHRt had a positive Covid: 64% had a positive test for SARS-CoV-2

    -- 76 of these NHRs participated in the 1^st point-prevalence survey on March 13

        -- 48 (63%) tested positive either initially or on subsequent surveys

            -- 17 (35%) reported typical symptoms, 4 (8%) reported only atypical symptoms, and 27 (56%) reported no new symptoms or changes in their chronic symptoms at the time of testing

            -- of the 27 patients classified as asymptomatic: 15 had no symptoms and 12 reported stable chronic symptoms

            -- 15 (56%) of the nursing residents who were asymptomatic at the time of testing had documented cognitive impairment (a similar percent to those who reported being symptomatic)

        -- 7 days after their positive test: 24 of the 27 asymptomatic NHRs (89%) had onset of symptoms and were recategorized has presymptomatic

        -- median time to symptom onset was 4 days

        -- most common symptoms were fever (71%), cough (54%) and malaise (42%)

-- viral growth on tissue culture was found for specimens obtained from 10 of the 16 residents with typical symptoms, 3 of 4 with atypical symptoms, and 17 of 24 who are presymptomatic, and one of 3 who remained asymptomatic (ie: viral viability was NOT related to stage of infection)

-- there was no correlation between PCR viral load and the number of days from the 1^st evidence of typical symptoms, and viral loads were consistently found to be positive in people were tested before typical symptom onset (of note, as with all of the SARS-CoV-2 viral load analyses, they measured the cycle threshold values, Ct , which are effectively the inverse of viral load, with a cutpoint of less than 40 being considered significant) 

-- viable virus was isolated from specimens collected 6 days before to 9 days after their 1^st evidence of typical symptoms

-- the doubling time for transmission of the virus was 3.4 days, vs 5.5 days in the local community

-- the outcomes in the patients were poor: by April 3, 11 of 57 residents were admitted to the hospital/3 in intensive care/and 15 had died (26%)

-- at the time of 1^st point prevalence testing on Marh 13, 11 of 138 full-time staff members (8%) tested positive for SARS-CoV-2; by March 26, 55 the staff had reported symptoms, 51 had been tested, and 26 (19%) were positive

-- all of the genetic sequences were identical or highly similar to those in previous analysis at the nursing home, suggesting the source of the virus was spread within the nursing home

Commentary:

-- this was a pretty remarkable study, in terms of displaying the rapid development of a systematic program for enforcing an aggressive protocol, testing lots of people and documenting in a granular way the evolution of the SARS-CoV-2 virus and its viability/likely transmissability [though, as per yesterday's blog http://gmodestmedblogs.blogspot.com/2020/04/covid-superiority-of-contact-tracing.html , it would have been great to test every health care worker and NHR regularly]

-- it is not surprising that the doubling time was so high in a nursing home, given the close contact with other residents as well as staff. Other studies have shown very high rates of Covid-19 in nursing home residents (and also lots of severe disease in this vulnerble population)

-- below is a figure from the article, showing that there was viable virus between 6 days before symptoms to 9 days afterwards, that there was no particular relationship between those with positive viral cultures and their viral loads  (this is inverse of Ct), including in those who were presymptomatic: ie people can have likely transmissible virus well before symptoms start and independent of the viral load on PCR (the caveat here is that viral growth on tissue culture is not necessarily translatable to human infection, though it’s pretty suggestive)

-- by their timetable of viral positivity it is highly likely that transmission from asymptomatic residents “contributed to the rapid and extensive spread of infection to other residents and staff”

-- a related issue, also from King County, found that 65% of health care personnel with Covid-19 worked when they were symptomatic, and 17% of symptomatic health care personnel initially had mild, nonspecific symptoms and no fever, cough, shortness of breath, or sore throat

   -- This all suggests that there has to be routine testing for healthcare workers. And for several reasons:

       -- many be may be asymptomatic and still have the ability to transmit the virus to others

       -- many may have symptoms that do not fit the criteria of our usual perception of Covid-19 (e.g. see blog on anosmia:http://gmodestmedblogs.blogspot.com/2020/04/covid-anosmia-extremely-common.html), and may ignore them and continue working with transmissable virus but nonspecific mild symptoms

       -- and some healthcare workers may also feel that they do not want to be a burden on other staff by not working if they are somewhat symptomatic, or perhaps lose their sick/vacation time by missing work

       -- but the bottom line is that sole reliance on symptom-based strategies in health care workers are probably ineffective in excluding workers from the workplace and preventing their transmitting virus to other workers and patients

-- limitations to the overall generalizability of the study include the fact that this was a nursing home population, with people living in close quarters, with a high incidence of cognitive dysfunction. The strengths of the study is the level of meticulous documentation.

So, this study adds strongly to the blog from yesterday (http://gmodestmedblogs.blogspot.com/2020/04/covid-superiority-of-contact-tracing.html) highlighting the fact that this SARS-CoV-2 virus is pretty sneaky:

-- the virus is shed at very high titers and seems to be viable almost a week prior to people becoming symptomatic

-- and, as per some other smaller studies (eg see http://gmodestmedblogs.blogspot.com/2020/03/covid-19-update-31120.html from 6 weeks ago), the viral loads as well as the culturable virus decreases after about the 1^st week of symptoms (though, per other studies including the blog from yesterday, patients are often sick for 3 weeks or more: ie, we are missing the boat on finding transmissible virus when we wait to test people who are "classically" sick with the virus for many days)

So the clear bottom line: if we want to rid ourselves of this virus, we need to do vigorous testing of people at risk, including those living in confined areas or with lots of social contact (e.g. as in homeless people in Boston per below, or the nursing home studies, or prison studies), or those with personal contact with patients having SARS-CoV-2, or health care workers or first responders, or those living in an area with a high level of virus positivity. Finding these people who are positive gives us a chance to enforce higher levels of quarantine/social isolation (as done in China and other countries). Our current strategy of testing basically only symptomatic patients is fundamentally flawed, leads to a false sense that we are testing the right people (creating the impression that asymptomatic or minimally symptomatic patients are not infectious) and is missing the largest group of highly infectious  people who will keep spreading the virus...

see http://gmodestmedblogs.blogspot.com/2020/04/covid-remdesivir-may-help-asymptomatic.html for a pretty scary study on high rate of SARS-CoV-2 in asymptomatic homeless people

geoff

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