Medium-term scenarios of COVID-19 as a function of immune uncertainties and chronic disease (preprint)

As the SARS-CoV-2 trajectory continues, the longer-term immuno-epidemiology of COVID-19, the dynamics of Long COVID, and the impact of escape variants are important outstanding questions. We examine these remaining uncertainties with a simple modelling framework that accounts for multiple (antigenic) exposures via infection or vaccination. If immunity (to infection or Long COVID) accumulates rapidly with the valency of exposure, we find that infection levels and the burden of Long COVID are markedly reduced in the medium term. More pessimistic assumptions on host adaptive immune responses illustrate that the longer term burden of COVID-19 may be elevated for years to come. However, we also find that these outcomes could be mitigated by the eventual introduction of a vaccine eliciting robust (i.e. durable, transmission-blocking and/or 'evolution-proof') immunity. Overall, our work stresses the wide range of future scenarios that still remain, the importance of collecting real world epidemiological data to identify likely outcomes, and the crucial need for the development of a highly effective transmission-blocking, durable, and broadly-protective vaccine.

Vaccine nationalism and the dynamics and control of SARS-CoV-2 (preprint)

Vaccines provide powerful tools to mitigate the enormous public health and economic costs that the ongoing SARS-CoV-2 pandemic continues to exert globally, yet vaccine distribution remains unequal between countries. To examine the potential epidemiological and evolutionary impacts of 'vaccine nationalism', we extend previous models to include simple scenarios of stockpiling. In general, we find that stockpiling vaccines by countries with high availability leads to large increases in infections in countries with low vaccine availability, the magnitude of which depends on the strength and duration of natural and vaccinal immunity. Additionally, a number of subtleties arise when the populations and transmission rates in each country differ depending on evolutionary assumptions and vaccine availability. Furthermore, the movement of infected individuals between countries combined with the possibility of increases in viral transmissibility may greatly magnify local and combined infection numbers, suggesting that countries with high vaccine availability must invest in surveillance strategies to prevent case importation. Dose-sharing is likely a high-return strategy because equitable allocation brings non-linear benefits and also alleviates costs of surveillance (e.g. border testing, genomic surveillance) in settings where doses are sufficient to maintain cases at low numbers. Across a range of immunological scenarios, we find that vaccine sharing is also a powerful tool to decrease the potential for antigenic evolution, especially if infections after the waning of natural immunity contribute most to evolutionary potential. Overall, our results stress the importance of equitable global vaccine distribution.

Assessing the influence of climate on future wintertime SARS-CoV-2 outbreaks (preprint)

High susceptibility has limited the role of the climate in the SARS-CoV-2 pandemic to date. However, understanding a possible future effect of climate, as susceptibility declines and the northern-hemisphere winter approaches, is an important open question. Here we use an epidemiological model, constrained by observations, to assess the sensitivity of future SARS-CoV-2 disease trajectories to local climate conditions. We find this sensitivity depends on both the susceptibility of the population and the efficacy of non-pharmaceutical controls (NPIs) in reducing transmission. Assuming high susceptibility, more stringent NPIs may be required to minimize outbreak risk in the winter months. Our results imply a role for meteorological forecasts in projecting outbreak severity, however, reducing uncertainty in epidemiological parameters will likely have a greater impact on generating accurate predictions and reflects the strong leverage of NPIs on future outbreak severity.

High variation expected in the pace and burden of SARS-CoV-2 outbreaks across sub-Saharan Africa (preprint)

A surprising feature of the SARS-CoV-2 pandemic to date is the low burdens reported in sub-Saharan Africa (SSA) countries relative to other global regions. Potential explanations (e.g., warmer environments [1], younger populations [2,3,4]) have yet to be framed within a comprehensive analysis accounting for factors that may offset the effects of climate and demography. Here, we synthesize factors hypothesized to shape the pace of this pandemic and its burden as it moves across SSA, encompassing demographic, comorbidity, climatic, healthcare and intervention capacity, and human mobility dimensions of risk. We find large scale diversity in probable drivers, such that outcomes are likely to be highly variable among SSA countries. While simulation shows that extensive climatic variation among SSA population centers has little effect on early outbreak trajectories, heterogeneity in connectivity is likely to play a large role in shaping the pace of viral spread. The prolonged, asynchronous outbreaks expected in weakly connected settings may result in extended stress to health systems. In addition, the observed variability in comorbidities and access to care will likely modulate the severity of infection: We show that even small shifts in the infection fatality ratio towards younger ages, which are likely in high risk settings, can eliminate the protective effect of younger populations. We highlight countries with elevated risk of slow pace, high burden outbreaks. Empirical data on the spatial extent of outbreaks within SSA countries, their patterns in severity over age, and the relationship between epidemic pace and health system disruptions are urgently needed to guide efforts to mitigate the high burden scenarios explored here.

Immuno-epidemiological life-history and the dynamics of SARS-CoV-2 over the next five years (preprint)

Uncertainty in the immune response to SARS-CoV-2 may have implications for future outbreaks. We use simple epidemiological models to explore estimates for the magnitude and timing of future Covid-19 cases given different impacts of the adaptive immune response to SARS-CoV-2 as well as its interaction with vaccines and nonpharmaceutical interventions. We find that variations in the immune response to primary SARS-CoV-2 infections and a potential vaccine can lead to dramatically different immunity landscapes and burdens of critically severe cases, ranging from sustained epidemics to near elimination. Our findings illustrate likely complexities in future Covid-19 dynamics, and highlight the importance of immunological characterization beyond the measurement of active infections for adequately characterizing the immune landscape generated by SARS-CoV-2 infections.

The impact of COVID-19 non-pharmaceutical interventions on the future dynamics of endemic infections (preprint)

Non-pharmaceutical interventions (NPIs) have been employed to reduce the transmission of SARS-CoV-2, yet these measures are already having similar effects on other directly-transmitted, endemic diseases. Disruptions to the seasonal transmission patterns of these diseases may have consequences for the timing and severity of future outbreaks. Here we consider the implications of SARS-CoV-2 NPIs for two endemic infections circulating in the United States of America (USA): respiratory syncytial virus (RSV) and seasonal influenza. Using laboratory surveillance data from 2020, we estimate that RSV transmission declined by at least 20% in the USA at the start of the NPI period. We simulate future trajectories of both RSV and influenza, using an epidemic model. As susceptibility increases over the NPI period, we find that substantial outbreaks of RSV may occur in future years, with peak outbreaks likely occurring in the winter of 2021-2022. Results for influenza broadly echo this picture, but are more uncertain; future outbreaks are likely dependent on the transmissibility and evolutionary dynamics of circulating strains.

Susceptible supply limits the role of climate in the COVID-19 pandemic (preprint)

Preliminary evidence suggests that climate may modulate the transmission of SARS-CoV-2. Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic probing different scenarios of climate-dependence based on known coronavirus biology. We find that while variations in humidity may be important for endemic infections, during the pandemic stage of an emerging pathogen such as SARS-CoV-2 climate may drive only modest changes to pandemic size and duration. Our results suggest that, in the absence of effective control measures, significant cases in the coming months are likely to occur in more humid (warmer) climates, irrespective of the climate-dependence of transmission and that summer temperatures will not substantially limit pandemic growth.