COVID: kids as vectors; school closure effects

Are kids important vectors of SARS-CoV-2 to others? There was a recent study suggesting this was not an important means of viral spread, but 2 recent ones suggest the opposite, one assessing SARS-
CoV-2 viral loads in kids and the other the effect of school closures on Covid-19 incidence and mortality. 

of note, this blog happened to occur just after the Trump campaign had a video kicked off facebook (no mean feat) that claimed that children were immune to the coronavirus!!!!!  see https://www.nytimes.com/2020/08/05/technology/trump-facebook-coronavirus-video.html?campaign_id=9&emc=edit_nn_20200806&instance_id=21016&nl=the-morning&regi_id=96969620&segment_id=35387&te=1&user_id=9c29d7c2cb929bcf778e5e0423eca07b .  pretty shocking (i will refrain, unusually, from my usual expletives here)

 

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A recent Letter to the Editor found that younger kids actually had significantly higher SARS-CoV-2 viral loads than older kids or adults (see covid kids high viral load jama2020 in dropbox, or doi:10.1001/jamapediatrics.2020.3651. 

 

Details: 

--145 patients with mild-to-moderate Covid-19 illness were assessed within 1 week of symptom onset, from a pediatric tertiary medical center in Chicago 

    -- 46 children <5yo; 51 aged 5-17; 48 adults aged 18-65 

 

Results: 

--PCR cycle thresholds (the inverse of viral loads: the lower the Ct, the higher the viral load; below 40 being considered significant), noting median Ct values and interquartile ranges: 

    --age <5: 6.5 (4.8-12.0) 

    --age 5-18: 11.1 (6.3-15.7) 

    --age 18-65: 11.0 (6.9-17.5) 

 

Commentary: 

--they found an impressively higher viral load in kids <5yo, with no difference between kids 5-17 and adults, which translates to 10-fold to 100-fold more virus in the upper respiratory tract of those <5yo

--this study measured PCR cycle thresholds (the inverse of viral loads), and this does not necessarily reflect transmissible virus. However, there is a correlation in kids between higher PCR-based viral loads and culturable virus (this is also still a lab and not clinical finding, though very likely represents viable virus in people) 

--of course, one of the larger challenges with little kids is how to ensure social distancing, use of masks, avoiding the social interactions with other kids (perhaps in day care or school), all of which do function well in preventing SARS-CoV-2 transmission in general

--it is unclear how to piece this all together in a coherent model: 

    -- studies have found lower ACE-2 levels in the nasal mucosa of kids (ACE-2 being the receptors for SARS-CoV-2, allowing for cellular entry), with that finding being cited as the reason that kids may have less severe infections. 

    -- so, the higher viral load in the young ones does not seem to translate into more severe infections. Is this because there are fewer ACE2 receptors leading to less intracellular virus, less illness, and more virus around to be quantified by PCR??   

    -- but, the higher viral load would still likely make the virus even more communicable to others (and, by the way, there has been documentation of viral shedding in asymptomatic kids) 

--one conclusion is that young children might be a very important target for vaccination (esp with the combo of high viral loads and harder to self-isolate) and hopefully will be included in the vaccination studies, ongoing and future vaccination 

 

  

Another article did sophisticated mathematical modeling to assess the differences between states doing early vs late school closings on Covid-19 incidence and mortality (see covid school closures dec spread jama2020 in dropbox, or doi:10.1001/jama.2020.14348) 

 

Details: 

-- a population-based study of all 50 US states, conducted between March 9 and May 7, comparing the progression of the population-based incidence of Covid-19 infection and Covid-related deaths in states with varying times to school closure, for children in grades K-12 

-- data on daily Covid-19 incidence and mortality were from the Johns Hopkins University School of Public Health 

-- for each state, they considered the following four nonschool-related nonpharmaceutical interventions: stay-at-home or shelter-in-place orders, nonessential business closure, restaurant and bar closure, prohibition of gatherings of more than 10 people 

    -- 39 states enacted all 4 nonpharmaceutical interventions 

    -- states with the highest cumulative incidence of Covid-19 cases enacted multiple nonpharmaceutical interventions over shorter periods of time 

-- given differences in SARS-CoV-2 testing, they included an assessment of the daily cumulative number of tests per 1000 residents 

-- they also assessed : 

    --the urban population density of the states, the percentage of the states’ populations with obesity, the percentage of people 15 yo or younger, the percentage of those aged over 65, and  the number of nursing home residents per 1000 population 

    --the CDC social vulnerability index (socioeconomic status, household composition, disability status, race and ethnicity, English language proficiency, housing type, transportation access) 

 

--baseline Covid-19 cumulative incidence in states at the time of school closure ranged from 0 to 14.75 cases /100,000 population 

--median time from school closure to the last enacted nonpharmaceutical intervention was 12 days 

  

Results: 

--Covid-19 incidence, in their adjusted analysis (the relative change varied significantly by testing rate per thousand residents, percentage of states population aged 65 or older, number of nursing home residents per thousand population, and urban density) 

    --baseline overall relative change in Covid incidence was 220% per week,or 265% per week in adjusted model 

    -- after school closings, the overall combined composite relative weekly change was 10% (1%-18%) [this composite change is a combination of changes related to school closures and nonschool-related changes] 

    -- school closures were associated  with a 62% (49%-71%) reduction in Covid-19 cases 

   -- the absolute effects over a 26 day period after school closure (assuming there would be linear growth): 638.7 cases per 100,000 that would have occurred had the schools remained open, 214.8 cases per 100,000 estimated in the school closure model, creating a difference of 423.9 cases per 100,000 likely prevented by school closures

-- results stratified by incidence of Covid-19: 

    -- the states that closed early, when the cumulative incidence of Covid was lowest, had a 72% (62%-79%) reduction in Covid cases, vs the states that were slowest  to close having the highest cumulative incidence of Covid, a 49% (33%-62%) reduction  

    -- school closings in areas with the lowest quartile of Covid incidence vs the highest quartile: 128.7 fewer cases per 100,000 population over 26 days and 1.5 fewer deaths per 100,000 population over 16 days 

  

-- Covid-related mortality, in the adjusted analysis: 

    -- baseline mortality increased 186% per week

    -- combined composite relative weekly change in mortality after school closure: 2% (-8% to 14%) 

    -- by examining only school closure: relative decrease per week in mortality was 58% (46%-67%) 

    -- this relative change was highest in states with the lowest cumulative Covid-19 incidence at the time of school closure, 64% decrease (52%-73%) vs 53% (40%-63%) in those schools that closed later 

    -- this relative change in mortality by school closure varied significantly by restaurant/bar closure and urban density 

    -- the absolute effects associated with school closure during the 16 day period after school closure (assuming linear growth) was 19.4 deaths per 100,000 that would have occurred if schools remained opened 

        -- compared with the 6.8 deaths per 100,000 estimated for the school closure model, the absolute difference associated with school closure was 12.6 deaths per 100,000 likely prevented

  

--these numbers, when extrapolated to the 322.2 million people in the country, translate to 1.37 million fewer cases of Covid-19 over a 26-day period and 40,600 fewer deaths over a 16-day period 

  

Commentary: 

--US states closed K-12 schools and children in daycare centers in March, over a 10 day period. Colleges soon followed. School closings also occurred in 192 other countries, affecting more than 90% of the world’s students (1.6 billion) 

-- this study found that school closures were associated  with a 62% reduction in Covid-19 cases, and a 58% reduction in Covid-associated mortality 

    -- it is important to remember that these were relative changes; changes in the absolute same number of cases in a low incidence state vs high incidence state will be represented by hugely different relative risks 

-- several earlier studies have found a demonstrated association between school closure and reduced transmission of influenza 

--a couple of very recent findings related to school reopening: 

    --an Indiana school opened but then closed within the first day after a kid tested positive for coronavirus: https://www.nytimes.com/2020/08/01/us/schools-reopening-indiana-coronavirus.html , and schools will now be closed in Indiana through the end of the year for grades K-12 (https://www.indystar.com/story/news/education/2020/04/02/coronavirus-indiana-schools-closed-through-end-academic-year/5110846002/ ) 

    --Israel did a great job early in decreasing covid-19 cases, but then re-opened schools rather quickly with disastrous results: see https://www.nytimes.com/2020/08/04/world/middleeast/coronavirus-israel-schools-reopen.html?referringSource=articleShare 

 

Limitations of the study 

--the study was based on available observational data, with uncertainties about non-measured differences (eg, in hand-washing, proper use of masks, use of distancing and masks inside houses, etc)

--it is hard to quantify some of the effects of messaging: those schools that shut down later may well have been in areas of the country where local governmental leaders minimized the gravity of the situation with Covid-19 and may have been dismissive not only of use of PPE and social distancing, but also the appropriateness of these and other extremely important disease preventing measures, leading to perhaps subtle and unmeasured differences in actual viral exposure between states 

    --in fact, the sheer complexity of the study design, adjusting for many diverse differences in states (testing capacity, who was tested, population density and distribution, health status, social vulnerability) all leads to more appropriate data, but the complexity of the mathematical modeling adds to the potential of aggregate errors in their data 

-- there also might be considerable differences in the definition of Covid-19 cases (perhaps related to the intensity of testing, and the criteria for testing: eg, some states limited testing to hospitalized patients), as well as Covid-related deaths (coding deaths is likely a problem everywhere, but perhaps more common in states that were less interested/consistent in identifying Covid as a cause of mortality) 

 

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and, there was an impressive editorial accompanying the article (see covid school closure edit jama2020 in dropbox,or doi:10.1001/jama.2020.13092), elaborating on some of the consequences of school closings, which I will incorporate into my overall conclusions below

 

 

so, many thoughts on the diverse information above: 

--it seems pretty clear, in the aggregate of studies, that kids are likely an important vector for coronavirus transmission. And, schools seem to be an important place where social interactions and lack of aggressive nonpharmaceutical interventions likely furthered the spread of the virus there, which can then brought home to others 

--we do know that there is a strong relationship between education, income and life expectancy: 

    -- some of the harms of school closures:  economic analyses suggest that school disruptions from war and teacher strikes are associated with projected annual income loss of 2 to 3% over the course of the affected students’ lifetimes; current economic models suggest that Covid-19 is estimated to diminish future earnings by $2.5 trillion!!! 

--schools also serve many other social functions: they are an essential source of meals and nutrition for kids in K-12 as well as behavioral supports, physical activity, social interaction, supports for students with special needs, and other vital resources for healthy development 

 

--we do not know the optimal duration of school closings, what the appropriate markers are for when to reopen, if there are more important nonpharmaceutical interventions that should be incorporated (especially in younger kids in school) and what combination of interventions are most effective. 

    --and we do not know the most effective way that schools should be re-opened in order to preserve the huge benefits of schools yet assure reasonably low public health risk. For example, given that classes should be less crowded to decrease viral spread, should kids themselves be stratified (some kids need the structure of the classroom more than others who are better self-learners with less hands-on teaching)?? or should the school sessions themselves be reconfigured for 1/2 day of in-school and 1/2 day of teleschooling fall all?? or... 

 

--and school closures are associated with profound effects on parents'/guardians' productivity: it is estimated that a 12-week school closing in the US would result in $128 billion in lost productivity 

--and, school closures are very likely to exacerbate the already huge inequities in our current system (given the already big differences in resources available to schools and families), including: 

    -- kids in less well-resourced neighborhoods have more limited access to computers and the Internet, and help at home to use these resources well (especially important for the younger kids), and have more need for the other school-based services 

--and, I think that we, as medical people, may overemphasize the medical implications of this virus, in light of its highly evolved state to infect maximal numbers of people and wreak general havoc from both the potentially dire short-term effects as well as the documented longer-term effects (more and more are being identified: cardiac, neuro, psych…). it is impossible now to balance well the quite profound downsides of school closures along with the huge public health threat

 

-- though, as a society, I think the virus does provide us with an opportunity (?imperative) to evaluate the really profound social effects of the virus, which are more profound in the US than in many other countries, since we have such a minimal social safety net: 

    --the effects of kids being out of school and without daycare (for the young ones) or just needing attention at home, making it hard for their caretakers to work  even if their workplaces are functioning

    --for those "furloughed", the effects of lost wages on the livelihood of the majority of Americans who do not have adequate savings to provide for their essential daily needs 

    --the effects of lost health insurance (since most get health care through the antiquated system of employer-based insurance), especially an issue in the many states with inadequate Medicaid programs to provide coverage (esp those that did not accept the Medicaid expansion from Obamacare). And, meds are dramatically overpriced, especially for the uninsured (eg see http://gmodestmedblogs.blogspot.com/2018/12/high-insulin-cost-leads-to-underuse.html) 

--so, the issue now, it seems to me, is how to use this current disasterous coronavirus situation to try to deal with the underlying social issue of baseline inequities: inadequate basic systems to support the most vulnerable population, which really is the vast majority of people in the US (given that most people live within 1-2 paychecks of being able to support themselves/families). and this includes fixing the broken health care system that does not provide quality care to all, in the mix of the many social problems...

geoff

 

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