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COVID-19: What is the Denominator

Since the 1st cases of infection by SARS-CoV-2 were reported in China, we have all been confronted by death and case-fatality statistics, which are both misleading and inaccurate. As of this morning, 2837 from a total of 83 774 reported cases of COVID-19 were fatal. Public Health professionals, the lay public, and politicians will conclude that this disease carries a “mortality rate” of 3.4%. Relatively few realize that “only” 1.4% of patients treated outside of Mainland China have died of COVID-19: 0.7% of passengers on the Diamond Princess cruise ship, 0.5% of patients in South Korea, etc.

One explanation for these discrepant case-fatality statistics is related to demography. Patients reported by official sources have a higher mean age and prevalence of underlying chronic disease than the general Chinese population (or international travelers). Case-definition, variation in quality of care, genetic and nutritional factors might also explain higher fatality rates among Chinese patients. Indeed, several of the patients who died of COVID-19 outside of Mainland China have also been Chinese Nationals.

A fundamental error in all of this could be related to the term, “reported cases.” How many infections in China are asymptomatic or sub-clinical? If, for example, only one-in-10 individuals who acquire infection by SARS-CoV-2 are sufficiently ill to visit a clinic or hospital, the true case-fatality rate decreases from 3.4% to 0.34% A seroprevalence survey in the general population could easily determine the true impact of this disease.

This week, details of an antibody assay for SARS-CoV-2 infection were reported in Journal of Medical Virology. [1] The authors state that the procedure detects both IgM and IgG antibodies within 15 minutes, with a test sensitivity and specificity of 88.86% and 90.63%, respectively.

Beyond the search for vaccines and effective anti-viral agents, an immediate remedy for much of the uncertainty regarding COVID-19 will be a comprehensive serological survey of populations in affected areas. Tested individuals should be questioned regarding recent travel, occupational contact, and relevant symptoms which may have occurred during the preceding 2 months.

If a high background sero-prevalence rate exists among people in Wuhan (or China as a whole) COVID-19 becomes little more threatening than other “new strains of flu” that we deal with each year.

References:
1. Li S, Yi Y, Lou X, et al. 2020. Development and Clinical Application of a Rapid IgM‐IgG Combined Antibody Test for SARS‐CoV‐2 Infection Diagnosis. J Med Virol (ahead of print) PMID: 32104917 DOI: 10.1002/jmv.25727.

 

Note featured on ProMED

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