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As of May 2022, there have been 524,134,255 cases of COVID around the world. Over 6 million COVID deaths have been reported, sometimes referred to as six million excess deaths. Average daily cases can fluctuate greatly from place to place and some of that comes from challenges and lags in reporting probable cases or reporting probable deaths.
This makes it no surprise that for several years now, we have been inundated by reports summarizing incidence and mortality data for COVID-19 on both the national and global levels. This has left many wondering “Is COVID the new plague, and what do the death statistics tell us?”
During 541-542 C.E. Yersinia pestis, the bacterium that causes bubonic plague spread out from China into the Byzantine Empire. Few were spared, and an estimated 25 to 100 million Europeans went on to die during repeated waves of infection that struck the region over the next 200 years. As many as 5,000 plague deaths per day were recorded in the city of Constantinople. This “Justinian Plague” is named for Emperor Justinian, who managed to survive an attack of the illness (less-fortunate victims included Pope Pelagius II and Wighard, Archbishop of Canterbury).
In recent years, much has been written regarding the risk of the spread of infectious diseases related to global warming. There is some evidence that the Justinian plague was the product of global cooling. Five years before the pandemic, emissions from a volcano may have significantly lowered atmospheric temperature, resulting in the migration of rodents deprived of food. Fleas, which spread plague from rodents to humans, cannot efficiently digest their blood meals at low temperatures, causing them to vomit as they attempt to feed again – injecting contaminated material into their hosts. The Justinian plague largely spared the Arabian Peninsula, thus nourishing the rise of Islam and Arab armies, which quickly conquered large areas of a devastated Europe.
From 1347 to 1351, a second plague pandemic – The Black Death – killed 75 to 200 million humans – an estimated ten-to-sixty percent of the European population. Once again, the disease originated in Asia, entering through Sicily on Genoese galleys, and reaching Venice in 1348. The irony of a pestilence from China spreading through northern Italy is obvious in light of current events. Just as the Justinian Plague claimed the life of Bishop Wighard, the Black Death killed two Archbishops of Canterbury in a single year – Thomas Bradwardine and John de Ufford. Just as the Justinian Plague altered the future of Europe, the Black Death may well have paved a path to the Renaissance.
For now, there is little similarity between COVID-19 and Bubonic plague; but the current massive disruption of society will undoubtedly have consequences for human civilization in years to come. 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 can be both misleading and inaccurate.
As of February 29, 2020, 2837 from 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%. 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.
Later, as of March 12, 2020, 126,258 cases of COVID-19 had been reported worldwide; and 4,368 died of the disease – a case-fatality ratio (CFR) of 3.6%. This figure varies widely from country to country.
Indeed, The CFR in Mainland China is 3.9% – vs. 3.2% of all other countries combined. Only 1.0% of infected passengers aboard the Diamond Princess cruise ship died of the disease. Among countries reporting more than 500 cases to date, the CFR (in descending order) is Italy 6.6%, Iran 4.3%, Spain 2.8%, United States 2.8%, Japan 2.5%, France 2.1%, United Kingdom 1.7%, South Korea 0.8%, Netherlands 0.8% and Switzerland 0.7%. Fatal infection is notably rare among the Scandinavian countries: Sweden 0.2%, Norway 0%, Denmark 0%. Finland, which has experienced 109 cases, has reported zero mortality.
The CFR in each country is primarily determined by how the disease is identified, defined, and reported. The quality, training, professionalism, and available resources available Health-Care workers will also influence case-finding and treatment, as will Demographic and cultural differences related to age, nutrition, access to local health facilities, lifestyle, and exposure to animals. We’d suspect that much of this variation in CFR for COVID-19 is related to the very definition of “cases.” The death of an infected patient will be obvious and easily documented, while asymptomatic or relatively minor infections could remain undocumented. Indeed, the total number of “cases” used to calculate CFR might only represent those cases who are sufficiently ill to seek medical care. The patient with a mild febrile illness will not be “counted.”
These questions can be easily solved using a standard serological survey in relevant communities. Such a survey should include a questionnaire regarding recent symptoms, exposure, occupation, etc. Suppose a large proportion of the general population is seropositive toward the SARS-2 virus. We might conclude that the disease is less dangerous than current statistics seem to indicate.
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 the quality of care, and genetic and nutritional factors might also explain higher fatality rates among Chinese patients. Indeed, several of the patients who died of COVID-19 outside Mainland China have also been Chinese Nationals.
A fundamental error in all of this could be related to “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 actual case-fatality rate decreases from 3.4% to 0.34%. A seroprevalence survey in the general population could quickly determine the true impact of this disease.
Beyond the search for vaccines and effective antiviral agents, a comprehensive serological survey of populations in affected areas will immediately remedy much of the uncertainty regarding COVID-19. Tested individuals should be questioned regarding recent travel, occupational contact, and relevant symptoms which may have occurred during the preceding two months.
Details of an antibody assay for SARS-CoV-2 infection were reported in the Journal of Medical Virology.  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.
If a high background seroprevalence rate exists among people in Wuhan (or China), COVID-19 becomes a little more threatening than other “new strains of flu” that we deal with each year. The impact of future SARS-CoV-2 seroprevalence surveys will largely depend on the quality of the test itself, the duration of immunity and protective role of the antibody, and the possible emergence of newer strains of coronavirus, and other factors. Additional seroprevalence data will play a key role in planning our response to this pandemic.
Remember that “reported cases” cannot be equated with “total cases” without including individuals with asymptomatic sub-clinical infections that do not seek medical care. If a large segment of the population is seropositive, we might conclude that the actual case-fatality ratio of COVID-19 is lower than official data might suggest. A seroprevalence study reported this week provides solid evidence that this is the case.