Pandemic-stage propagation dynamics in South Africa suggest pre-existing cross-reactive protection against severe Covid-19 (preprint)

Early in the Covid-19 outbreak, it was speculated that pre-existing cross-reactive immunity from prior BCG vaccination or exposure to common cold human coronaviruses might confer some protection against Covid-19. Following a year of circulation of SARS-CoV-2 through the world, epidemiological dynamics allow a test of this hypothesis. A dynamic epidemiological model was fitted to the Covid-19 attributed ‘excess deaths’ in South Africa, a country with a long-standing BCG vaccination program and where social-economic circumstances potentially result in frequent exposure to common cold coronaviruses. We show that Covid-19 propagation dynamics in South Africa are consistent with an initially fully susceptible population (no prior cross-immunity protecting against infection), but this requires assuming values of the infection fatality rate (IFR) below or at the lower plausible range (0.31 to 0.53) of internationally reported values. This suggests that some form of pre-existing protection against severe Covid-19 may exist in South Africa. The observed disease propagation dynamics can be explained by both long-lasting immunity and various scenarios of reinfection in the presence of the more transmissible B.1.351 variant, which is also relatively resistant to antibodies induced by infections of prototype SARS-CoV-2. All scenarios of reinfection also require assuming a low IFR in order to replicate the observed attributes of the outbreak.

South African COVID-19 Epidemic Dynamics Are Consistent with Widespread Cross-Immunity (preprint)

The progression of the Covid-19 pandemic in South Africa, as measured by the number of deaths in excess of the seasonally-expected mortality, is inconsistent with infectivity and fatality rates estimated elsewhere in the world.A compartment model applied in prognostic and inverse mode was used to explore the combinations of key parameters that could account for the outbreak timing and magnitude of Covid-19 mortality in the Western Cape Province in South Africa, where information on reported cases and deaths are most reliable.If it is assumed that the entire population is susceptible, the total number of deaths by October 2020, after six months of propagation, is far lower than expected for fatality and infection rates in the plausible range. The unimodal infection peak, followed by a substantial decline coinciding with the relaxation of non-pharmacological interventions, suggests that herd immunity has been reached, but serological tests for exposure indicate that too few people have been infected for this to be the case. We show that the number of excess deaths, timing of the peak infection and proportion of the population infected can all be explained by assuming 30-40% pre-existing cross-immunity in the population.The dynamics of Covid-19 in South Africa cannot be explained under the assumption of a fully susceptible population. Rather than postulating, against the evidence, that the coronavirus exhibits fundamentally low infectivity or morbidity rates in South Africa, we point out that wide-spread, pre-existing cross-reactive immunity to SARS-CoV-2, could explain the observations. If this is the case, the likelihood of a large second wave is low if those infected do not rapidly lose immunity.Funding Statement: The salaries of Engelbrecht and Scholes are funded by the University of the Witwatersrand. Otherwise, no dedicated source of funding supported this research, and neither author received funding from any source to write the paper.Declaration of Interests: The authors have nothing to disclose.

Winter is Coming: A Southern Hemisphere Perspective of the Environmental Drivers of SARS-CoV-2 and the Potential Seasonality of COVID-19 (preprint)

SARS-CoV-2 virus infections in humans were first reported in December 2019, the boreal winter. The resulting COVID-19 pandemic was declared by the WHO in March 2020. By July 2020 COVID-19 is present in 213 countries and territories, with over 12 million confirmed cases and over half a million attributed deaths. Knowledge of other viral respiratory diseases suggests that the transmission of SARS-CoV-2 could be modulated by seasonally-varying environmental factors such as temperature and humidity. Many studies on the environmental sensitivity of COVID-19 are appearing online, and some have been published in peer-reviewed journals. Initially, these studies raised the hypothesis that climatic conditions would subdue the viral transmission rate in places entering the boreal summer and that southern hemisphere countries would experience enhanced disease. For the latter, the COVID-19 peak would coincide with the peak of the influenza season, increasing misdiagnosis and placing an additional burden on health systems. In this review, we assess the evidence that environmental drivers are a significant factor in the trajectory of the COVID-19 pandemic, globally and regionally. We critically assessed 42 peer-reviewed and 80 preprint publications that met qualifying criteria. Since the disease has been prevalent for only half a year in the northern, and a quarter of a year in the southern hemisphere, datasets capturing a full seasonal cycle in one locality are not yet available. Analyses based on space-for-time substitutions, i.e. using data from climatically distinct locations as a surrogate for seasonal progression, have been inconclusive. The reported studies present a strong northern bias. Socio-economic conditions peculiar to the ‘Global South’ have been omitted as confounding variables, thereby weakening evidence of environmental signals. We explore why research to date has failed to show convincing evidence for environmental modulation of COVID-19, and discuss directions for future research. We conclude that the evidence thus far suggests a weak modulation effect, currently overwhelmed by the scale and rate of the spread of COVID-19. Seasonally-modulated transmission, if it exists, will be more evident in 2021 and subsequent years.