COVID-19: effective nonmedical inteventions; other news

a recent mathematical modeling study based on Singapore suggested that quarantine, social/workplace distancing, and school closure were key to decreasing spread of SARS-CoV-2 (see covid nonmed interventions singapore lancetinfdz2020 in dropbox, or doi.org/10.1016/S1473-3099(20)30162-6)

Details:

-- mathematical modeling was based on:

    -- the FluTE influenza epidemic simulation model (accounts for demography, host movement, and social contact rates in workplaces, schools, and homes) to estimate the likelihood of human-to-human transmission of SARS-CoV-2 if local containment fails.

    -- the geographical, demographic, and epidemiologic model of Singapore were used as the synthetic but realistic representation of the Singaporean population at the household and individual levels, using national 2010 census data

    -- assumption that 7.5% of infections are asymptomatic (based on the flu data of 7.5%-22.7%), the mean incubation period was 5.3 days, and the duration of hospital stay after symptom onset was 3.5 days.

    -- assumption that asymptomatic individuals had a 50% decreased likelihood of transmission of the virus as compared to their symptomatic counterparts

    -- median age of the infection for all simulations was 37 years

-- the initial inquiry was based on predictions from the model at 80 days, with 100 initial local cases randomly among the resident population

-- they evaluated different R₀ values of 1.5, 2.0, and 2.5 (the R₀ is the basic reproduction number, representing the communicability of the virus, with an R₀ of 2 meaning that 2 people would likely be infected by a single person). 

-- based on the above, they assessed the following scenarios:

    -- isolation measures for infected individuals and quarantining family members, referred to as “quarantine”. Quarantine was expected to occur one day after symptom onset

         -- the healthcare facility was assumed to have 3000 beds maximum capacity. After full capacity was reached, family members of infected individuals were quarantined at home for 14 days/unable to attend work or school

    -- quarantine plus school closure for 2 weeks

    -- quarantine plus workplace distancing (in which 50% of the workforce was encouraged to work at home for 2 weeks)

    -- quarantine, social closure, and workplace distancing, referred to as “combined intervention”

-- they also did sensitivity analyses reflecting different levels of asymptomatic infections

Results:

-- R₀ = 1.5:

    -- at 80 days, median cumulative number of cases:

        -- baseline: 279,000 infections, 7.4% of the resident population

        -- quarantine: 15,000

        -- school closure (plus quarantine): 10,000

        -- workplace distancing (plus quarantine): 4000

        -- combined intervention: 1800, a reduction of 99.3%

-- R₀ = 2.0:

    -- at 80 days:

        -- baseline: 727,000 infections, 19.3% of the resident population

        -- quarantine: 130,000

        -- school closure: 97,000

        -- workplace distancing: 67,000

        -- combined intervention: 50,000, a reduction of 93.0%

-- R₀ = 2.5:

    -- at 80 days:

        -- baseline: 1,207,000 infections, 32% of the resident population

        -- quarantine: 520,000

        -- school closure: 466,000

        -- workplace distancing: 320,000

        -- combined intervention: 258,000, a reduction of 78.2%

-- when the community asymptomatic infection level increased to 22.7%:

    -- R₀ =  1.5: no intervention 340,000 cases (additional 61K); with quarantine 121,000 cases (additional 106K); with school closure 113,000 cases ( an additional 103K); with work-distancing 73,000 cases (addl 69K); with combined 58,000  (addl 56K)

    -- R₀ =  2.0: no intervention 829,000 cases (addl 102K); with quarantine 540,000 cases (additional 410K); with school closure 443,000 cases ( an additional 103K); with work-distancing 350,000 cases (addl 69K); with combined 361,000  (addl 56K)

    -- R₀ =  2.5: no intervention 1,294,000 cases (addl 77K); with quarantine 1,129,000 cases (additional 609K); with school closure 1,122,000 cases ( an additional 656K); with work-distancing 1,010,000 cases (addl 690K); with combined 991,000  (addl 733K)

Commentary:

-- in Singapore the 1^st case of COVID-19 was on January 23, 2020. As of March 16, patients with COVID-19 were isolated at the hospital they presented to or at the National Center for Infectious Diseases

-- the Singapore Ministry of Health implemented contact tracing to identify people near cases, and dispensed masks to household and public hospital emergency departments.

-- they calculated that school closure was less significant because in the early stage symptomatic children will have higher withdrawal rates from school than symptomatic adults from the workplace. Their model reflected a consistently lower likelihood of contagion in schools (see their Table for details)

--the numbers above are very sensitive (not surprisingly) to the asymptomatic rate and the R₀. we would need to do lots of testing of uninfected people to see what the asymptomatic rate is (though, for now, in the US we are only testing the very symptomatic ones, not even the ones with mild, prodromal symptoms…).

    --the asymptomatic percent in China was on the order of 1-3%; on the Diamond Princess cruise ship it was about 18% (see https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.10.2000180 ) …. 

    -- a recent CDC report from a Washington state skilled nursing facility (not the one documented previously) found a very rapid SARS-CoV-2 transmission rate: following a documented case of symptomatic COVID-19 in a health care worker, 76 of 82 residents were tested. 30% were positive, more than half of them were asymptomatic or presymptomatic when tested (10 of the residents were symptomatic at testing, but 13 residents were asymptomatic, 10 of whom did develop symptoms by 7 days later. (see https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e1.htm )

        --ie: as we know, symptom-based screening will not identify lots of infected people (and the limits on screening in the US is soooo highly problematic. hopefully will change dramatically when we actually have enough testing kits in the hopefully near future). 

        -- and, this report does suggest, but not confirm, that in this elderly population in a skilled nursing facility there was likely SARS-CoV-2 transmission from asymptomatic or minimally symptomatic people

    -- the R₀ of SARS-CoV-2 was extrapolated in China as between 1.4 and 6.49. we’ll see… current guesses are that it will be around the 2.0-2.5 range

--as reported broadly: the only way to really prevent SARS-CoV-2 outbreaks is through rigorous testing and surveillance, with quarantine of cases/contacts

--this analysis argues strongly for quarantining family and close contacts, no matter what the R₀ or the asymptomatic rates are

--limitations of the study: clearly this is mathematically modeling SARS-CoV-2 based on sophisticated models derived from influenza and applied to Singapore, so some of the inherent assumptions may well prove to be inaccurate. We do not have great info on the susceptibility of kids to SARS-CoV-2, or their likelihood of being asymptomatic (though overall they do tend to be less symptomatic)

So, several points:

--the numbers above are really scary. Huge numbers of infections anticipated just in Singapore, with the resultant huge numbers of very sick people and huge mortality. Especially when generalized to the world scale. And especially if the R₀ values and asymptomatic infection rates are on the higher sides

--there is considerable consolation that the likelihood of the social, non-medical interventions above will help. Fortunately, in many areas in the US we are promoting quarantine, schools have been closed, and workplaces have been shut down or transferred to home-based work. Unfortunately, unlike many countries in Europe, we do not have the social infrastructure to help workers who are laid off, have no income, and lose their health insurance. In many European countries, workers continue with 80-90% of their salaries when workplaces close (and, of course, they have universal health coverage anyway).

--we need to have much more preparedness for future inevitable outbreaks of aggressive viruses, since we have already seen several (SARS, MERS, etc) and there still are a large number of coronavirus species, for example, in animals that are likely at least as aggressive as our current SARS-CoV-2, waiting (lurking in the background) for a future attack

OTHER  NEWS:

As an anecdotal aside: there are reports from the ground in New York that many of the sick COVID-19 patients are going into renal failure and requiring emergent dialysis. And a case from Seattle of a patient with signficant mental status changes, but since the csf was non-inflammatory, SARS-CoV-2 PCR was not sent. one of the issues is that in these areas where there are lots of very sick patients with COVID-19, clinicians are so busy taking care of them that it is hard to get very detailed information now.

also, there is now a 5 minute point-of-care test approved by the FDA, per Abbot Labs (see https://abbott.mediaroom.com/2020-03-27-Abbott-Launches-Molecular-Point-of-Care-Test-to-Detect-Novel-Coronavirus-in-as-Little-as-Five-Minutes ). hopefully to be abundantly available soon

    --for example, a couple of patients at the Brigham and Womens Hospital in boston were admitted for surgery (not for infection) only to be found to have SARS-CoV-2 and potentially infecting >100 health care workers (and we do know that a significant source of infection is from infected health care workers). And now lots of workers who had at least 15 minutes of contact are supposed to be furloughed for 2 weeks, which will really deplete those needed to take care of patients (see https://edition.pagesuite.com/popovers/dynamic_article_popover.aspx?artguid=18d69204-c8ac-49d6-ac4b-4a74a066bef7&appid=1165 )

    -- we are so far behind where we need to be: not only in testing all patients admitted and all health care workers (esp with a rapid test), but still for basic supplies: the Brigham has enough N-95 masks for about 2 weeks only.  and the pandemic in Boston is now exploding. the Brigham, as part of the large and powerful Partners HealthCare conglomerate, was able to get a manufacturer to deliver more masks. but they had to go around the usual procedures of trying to buy masks on the open marketplace, only to be outbit by the Feds. but other, less connected and powerful hospitals/health care facilities, are in trouble....

And, the FDA approved a 15-minute antibody test (see https://techcrunch.com/2020/03/27/the-fda-just-okayed-multiple-15-minute-blood-tests-to-screen-for-coronavirus-but-there-are-caveats/ ), which can show old infections, and has important functions:

    --we can find out if people have had SARS-CoV-2 infections in the past; they now can work safely (ie, they seem to have at least short-term immunity)

    --there are promising studies that using convalescent serum from people with past infections may really help treat those with severe current infections (more details tomorrow)

geoff​

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