The interactions of SARS-CoV-2 with cocirculating pathogens: Epidemiological implications and current knowledge gaps.

Despite the availability of effective vaccines, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that cocirculation with other pathogens and resulting multiepidemics (of, for example, COVID-19 and influenza) may become increasingly frequent. To better forecast and control the risk of such multiepidemics, it is essential to elucidate the potential interactions of SARS-CoV-2 with other pathogens; these interactions, however, remain poorly defined. Here, we aimed to review the current body of evidence about SARS-CoV-2 interactions. Our review is structured in four parts. To study pathogen interactions in a systematic and comprehensive way, we first developed a general framework to capture their major components: sign (either negative for antagonistic interactions or positive for synergistic interactions), strength (i.e., magnitude of the interaction), symmetry (describing whether the interaction depends on the order of infection of interacting pathogens), duration (describing whether the interaction is short-lived or long-lived), and mechanism (e.g., whether interaction modifies susceptibility to infection, transmissibility of infection, or severity of disease). Second, we reviewed the experimental evidence from animal models about SARS-CoV-2 interactions. Of the 14 studies identified, 11 focused on the outcomes of coinfection with nonattenuated influenza A viruses (IAVs), and 3 with other pathogens. The 11 studies on IAV used different designs and animal models (ferrets, hamsters, and mice) but generally demonstrated that coinfection increased disease severity compared with either monoinfection. By contrast, the effect of coinfection on the viral load of either virus was variable and inconsistent across studies. Third, we reviewed the epidemiological evidence about SARS-CoV-2 interactions in human populations. Although numerous studies were identified, only a few were specifically designed to infer interaction, and many were prone to multiple biases, including confounding. Nevertheless, their results suggested that influenza and pneumococcal conjugate vaccinations were associated with a reduced risk of SARS-CoV-2 infection. Finally, fourth, we formulated simple transmission models of SARS-CoV-2 cocirculation with an epidemic viral pathogen or an endemic bacterial pathogen, showing how they can naturally incorporate the proposed framework. More generally, we argue that such models, when designed with an integrative and multidisciplinary perspective, will be invaluable tools to resolve the substantial uncertainties that remain about SARS-CoV-2 interactions.

Analysis of non-pharmaceutical interventions and their impacts on COVID-19 in Kerala.

In the absence of an effective vaccine or drug therapy, non-pharmaceutical interventions are the only option for control of the outbreak of the coronavirus disease 2019, a pandemic with global implications. Each of the over 200 countries affected has followed its own path in dealing with the crisis, making it difficult to evaluate the effectiveness of measures implemented, either individually, or collectively. In this paper we analyse the case of the south Indian state of Kerala, which received much attention in the international media for its actions in containing the spread of the disease in the early months of the pandemic, but later succumbed to a second wave. We use a model to study the trajectory of the disease in the state during the first four months of the outbreak. We then use the model for a retrospective analysis of measures taken to combat the spread of the disease, to evaluate their impact. Because of the differences in the trajectory of the outbreak in Kerala, we argue that it is a model worthy of a place in the discussion on how the world might best handle this and other, future, pandemics.

The pitfalls of inferring virus-virus interactions from co-detection prevalence data: application to influenza and SARS-CoV-2.

There is growing experimental evidence that many respiratory viruses-including influenza and SARS-CoV-2-can interact, such that their epidemiological dynamics may not be independent. To assess these interactions, standard statistical tests of independence suggest that the prevalence ratio-defined as the ratio of co-infection prevalence to the product of single-infection prevalences-should equal unity for non-interacting pathogens. As a result, earlier epidemiological studies aimed to estimate the prevalence ratio from co-detection prevalence data, under the assumption that deviations from unity implied interaction. To examine the validity of this assumption, we designed a simulation study that built on a broadly applicable epidemiological model of co-circulation of two emerging or seasonal respiratory viruses. By focusing on the pair influenza-SARS-CoV-2, we first demonstrate that the prevalence ratio systematically underestimates the strength of interaction, and can even misclassify antagonistic or synergistic interactions that persist after clearance of infection. In a global sensitivity analysis, we further identify properties of viral infection-such as a high reproduction number or a short infectious period-that blur the interaction inferred from the prevalence ratio. Altogether, our results suggest that ecological or epidemiological studies based on co-detection prevalence data provide a poor guide to assess interactions among respiratory viruses.