COVID: age-specific mortality

 A new meta-analysis updated older estimates of age-specific Covid-19 infection fatality rates (see covid fatality rates age-specific EurJEpidem2020 in dropbox, or https://doi.org/10.1007/s10654-020-00698-1 ).

Details:

--27 studies prior to 18Sept2020 from 34 geographical locations were evaluated in this systematic review

--age-specific infection fatality rates (IFRs) were computed using prevalence data and reported fatalities, 4 weeks after the midpoint of each of the studies (to compensate for lags in fatalities and reporting)

--to assess the prevalence of Covid infections, they used 2 approaches: 

    --seroprevalence in the population as determined by antibody screening: including representative population samples, as done in England, France, Ireland, Italy, Netherlands, Portugal, Spain, Geneva, and 4 US locations (Atlanta, Indiana, New York, and Salt Lake City);  and convenience samples (eg blood drawn for other reasons), as done in Belgium, Sweden, Ontario, and 8 US locations (Connecticut, Louisiana, Miami, Minneapolis, Missouri, Philadelphia, San Francisco, and Seattle)

    --comprehensive tracing programs doing extensive "live-virus PCR testing" of everyone with potential contact with an infected individual. they only included contact tracing studies that had strong, consistent public health programs with repeated tests of potentially infected individuals (eg Australia, Lithuania, New Zealand, Korea, and Iceland) [though sometimes PCR will pick up dead virus or viral fragments as well....]

Results:

--there was an exponential increase in IFRs over patient ages (see graph below; there was also a log-linear relationship on a different graph)

    --age 10: 0.002%

    --age 25: 0.01%

    --age 55: 0.4%

    --age 65: 1.4%

    --age 75: 4.6%

    --age 85: 15%

    -- >90yo: 25%

--range of IFRs: 0.5% in Salt Lake City and Geneva to 1.5% in Australia and England to 2.7% in Italy

--90% of the variation in population IFRs from different geographical locations was attributable to age differences and the extent that vulnerable age groups were infected with the virus

--in middle-aged groups, the annualized IFR for Covid was 2 orders of magnitude greater than the risk of fatal automobile accidents, and far more dangerous than influenza

    --age 45-54: automobile fatalities were 0.002% in England and 0.013% in US

    --age 75-84: automobile fatalities were 0.005% in England and 0.017% in US

Commentary:

-- accurate data on IFRs requires broad assessment of SARS-CoV-2 infection rates (prevalence of infection, including those with asymptomatic and mildly symptomatic infections), typically through antibody testing to assess seroprevalence 

    --for example, in New York City (population 8 million), a large seroprevalence study done in April found:

        -- 1.6 million estimated SARS-CoV-2 infections 

        -- 1.1 million symptomatic infections

        -- 220,000 reported cases of Covid-19

        -- 55,000 hospitalized patients

        -- 17,000 fatal outcomes

            --so, the reported Covid-19 mortality of about 10% really was about 1% (ie, if look at fatalities vs total estimated infections, and not fatalities vs reported cases)

            --and, antibody titers may wane over time (especially those targeting non-spike-specific antigens), so even the above numbers are likely underestimates

--the inclusion of the contact tracing component of the prevalence study, as done in several studies, does add another dimension to the seroprevalence data, in that it used the PCR test for the virus. though, per their graph above, the spread of results was pretty similar independent of the method of ascertaining prevalence

--the above study confirmed the well-known finding that age is important, but extends it to show that the actual IFRs were quite consistent between many geographical areas when corrected for age (to the 90th percentile). 

    --so the issue overall is largely independent of the treatments done (which did vary over the timespan of the individual studies done, and in different geographical areas), but the ages of the people infected. 

        --unfortunately, they did not have info on comorbidities, which often do track with age, and this really might be very important: not all 60yo's have the same likely IFR...

    --and those countries where lots of younger people get infected may have a lower overall IFR at that time, but that IFR likely changed dramatically as these younger people go on to infect their older relatives/coworkers/associates.

--and the relative numbers of fatalities by car accidents is 100-200x lower than from Covid. Per the WHO, the case fatality rates of influenza are well below 0.1%

Limitations:

--the SARS-CoV-2 prevalence rates from the different studies were based on different patient samplings: 

    --some had representative samples of the general population, others convenience samples for patients getting lab tests for other reasons; some presented raw data on antibody test results, others adjusted for the sensitivity/specificity of the antibody tests (and the different antibody tests used vary significantly in sensitivity/specificity). [this is general problem with systematic reviews/meta-analyses: putting together studies with differing methodologies to get a combination result]

    --also, prevalence data based on contact tracing is potentially limited by the extent of completeness of the contact tracing

--the data from the different countries was compiled at different times, so they may not be totally consistent (eg, changes in population self-protective strategies, effective medical therapies, local infection rates, etc  over time)

--they did not include other important psychosocial factors, including access to health care, living conditions, housing/food insecurity, etc etc

so, this recent article updates the infection fatality rates for people of different ages infected with SARS-CoV-2 virus.  My concern (and the reason i am doing this blog) is that we (globally) seem to have more inertia over time, being less concerned with aggressive disease prevention (avoiding social contacts, use of personal protective equipment/distancing). The huge increases in the current wave of infections are being met with less fear/anxiety and more complacency (eg more traveling, more time spent with others). This study gives a perspective of how these rates compare to other common problems (car accidents, influenza), suggesting that Covid-related fatality rates should really be seen as unacceptably high (and not some "new normal"). And, this focus on fatality rates does not include the huge burden of longer-term effects from Covid (see http://gmodestmedblogs.blogspot.com/2021/01/covid-longer-term-sequelae-and-new.html )

the advent of highly effective vaccines is a dramatic light at the end of the tunnel, BUT

--getting people vaccinated will take many months. so, we all just need to hunker down a bit longer (but at least now we can see that this viral affliction will abate at some time soon. so, hunkering down now has a more likely end than we thought last March)

--but in order to get the level of herd immunity to protect us all, we need to make sure that people get vaccinated:

    --one of the real pluses of the Moderna vaccine trial is that they really did not exclude many people (though they did exclude pregnancy, and there were not lots of really sicker individuals involved in the study). at this point it does seem that the mRNA vaccines work quite well on a population basis (see http://gmodestmedblogs.blogspot.com/2020/12/covid-moderna-mrna-vaccine-review.html )

    --there are still a fair number of anti-vaxers (those still mired in the non-science of autism etc related adverse effects of vaccinations, often springing from now well-known incorrect associations with MMR vaccines, and, it turns out, MMR vaccines are particularly important given the huge transmissibility of measles virus and the very well-known myriad of really bad potential problems)

        --but, maybe maybe even these anti-vaxers will be open to the vaccine as they see more and more people in their communities having bad infections/bad outcomes?????  recent polling suggests more people are willing to get the vaccine now.

geoff

 

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