Is increased mortality by multiple exposures to COVID-19 an overseen factor when aiming for herd immunity?

BACKGROUND: Governments across the globe responded with different strategies to the COVID-19 pandemic. While some countries adopted measures, which have been perceived controversial, others pursued a strategy aiming for herd immunity. The latter is even more controversial and has been called unethical by the WHO Director-General. Inevitably, without proper control measures, viral diversity increases and multiple infectious exposures become common, when the pandemic reaches its maximum. This harbors not only a potential threat overseen by simplified theoretical arguments in support of herd immunity, but also deserves attention when assessing response measures to increasing numbers of infection. METHODS AND FINDINGS: We extend the simulation model underlying the pandemic preparedness web interface CovidSim 1.1 (http://covidsim.eu/) to study the hypothetical effect of increased morbidity and mortality due to 'multi-infections', either acquired at by successive infective contacts during the course of one infection or by a single infective contact with a multi-infected individual. The simulations are adjusted to reflect roughly the situation in the USA. We assume a phase of general contact reduction ("lockdown") at the beginning of the epidemic and additional case-isolation measures. We study the hypothetical effects of varying enhancements in morbidity and mortality, different likelihoods of multi-infected individuals to spread multi-infections and different susceptibility to multi-infections in different disease phases. It is demonstrated that multi-infections lead to a slight reduction in the number of infections, as these are more likely to get isolated due to their higher morbidity. However, the latter substantially increases the number of deaths. Furthermore, simulations indicate that a potential second lockdown can substantially decrease the epidemic peak, the number of multi-infections and deaths. CONCLUSIONS: Enhanced morbidity and mortality due to multiple disease exposure is a potential threat in the COVID-19 pandemic that deserves more attention. Particularly it underlines another facet questioning disease management strategies aiming for herd immunity.

The impact of COVID-19 vaccination campaigns accounting for antibody-dependent enhancement.

BACKGROUND: COVID-19 vaccines are approved, vaccination campaigns are launched, and worldwide return to normality seems within close reach. Nevertheless, concerns about the safety of COVID-19 vaccines arose, due to their fast emergency approval. In fact, the problem of antibody-dependent enhancement was raised in the context of COVID-19 vaccines. METHODS AND FINDINGS: We introduce a complex extension of the model underlying the pandemic preparedness tool CovidSim 1.1 (http://covidsim.eu/) to optimize vaccination strategies with regard to the onset of campaigns, vaccination coverage, vaccination schedules, vaccination rates, and efficiency of vaccines. Vaccines are not assumed to immunize perfectly. Some individuals fail to immunize, some reach only partial immunity, and-importantly-some develop antibody-dependent enhancement, which increases the likelihood of developing symptomatic and severe episodes (associated with higher case fatality) upon infection. Only a fraction of the population will be vaccinated, reflecting vaccination hesitancy or contraindications. The model is intended to facilitate decision making by exploring ranges of parameters rather than to be fitted by empirical data. We parameterized the model to reflect the situation in Germany and predict increasing incidence (and prevalence) in early 2021 followed by a decline by summer. Assuming contact reductions (curfews, social distancing, etc.) to be lifted in summer, disease incidence will peak again. Fast vaccine deployment contributes to reduce disease incidence in the first quarter of 2021, and delay the epidemic outbreak after the summer season. Higher vaccination coverage results in a delayed and reduced epidemic peak. A coverage of 75%-80% is necessary to prevent an epidemic peak without further drastic contact reductions. CONCLUSIONS: With the vaccine becoming available, compliance with contact reductions is likely to fade. To prevent further economic damage from COVID-19, high levels of immunization need to be reached before next year's flu season, and vaccination strategies and disease management need to be flexibly adjusted. The predictive model can serve as a refined decision support tool for COVID-19 management.