Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period

Abstract

It is urgent to understand the future of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) transmission. We used estimates of seasonality, immunity, and cross-immunity for betacoronaviruses OC43 and HKU1 from time series data from the USA to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained since a resurgence in contagion could be possible as late as 2024.

The ongoing severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) pandemic has caused nearly 500,000 detected cases of coronavirus disease 2019 (COVID-19) illness and claimed over 20,000 lives worldwide as of 26 Mar 2020 (1). Experience from China, Italy, and the United States demonstrates that COVID-19 can overwhelm even the healthcare capacities of well-resourced nations (2–4). With no pharmaceutical treatments available, interventions have focused on contact tracing, quarantine, and social distancing. The required intensity, duration, and urgency of these responses will depend both on how the initial pandemic wave unfolds and on the subsequent transmission dynamics of SARS-CoV-2. During the initial pandemic wave, many countries have adopted social distancing measures, and some, like China, are gradually lifting them after achieving adequate control of transmission. However, to mitigate the possibility of resurgences of infection, prolonged or intermittent periods of social distancing may be required. After the initial pandemic wave, SARS-CoV-2 might follow its closest genetic relative, SARS-CoV-1, and be eradicated by intensive public health measures after causing a brief but intense epidemic (5). Increasingly, public health authorities consider this scenario unlikely (6). Alternatively, the transmission of SARS-CoV-2 could resemble that of pandemic influenza by circulating seasonally after causing an initial global wave of infection (7). Such a scenario could reflect the previous emergence of known human coronaviruses from zoonotic origins e.g. human coronavirus (HCoV) OC43 (8). Distinguishing between these scenarios is key for formulating an effective, sustained public health response to SARS-CoV-2.

The pandemic and post-pandemic transmission dynamics of SARS-CoV-2 will depend on factors including the degree of seasonal variation in transmission, the duration of immunity, and the degree of cross-immunity between SARS-CoV-2 and other coronaviruses, as well as the intensity and timing of control measures. SARS-CoV-2 belongs to the betacoronavirus genus, which includes the SARS-CoV-1 coronavirus, MERS coronavirus, and two other human coronaviruses, HCoV-OC43 and HCoV-HKU1. The SARS-CoV-1 and MERS coronaviruses cause severe illness with approximate case fatality rates of 9 and 36% respectively, but the transmission of both has remained limited (9). HCoV-OC43 and HCoV-HKU1 infections may be asymptomatic or associated with mild to moderate upper respiratory tract illness; these HCoVs are considered the second most common cause of the common cold (9). HCoV-OC43 and HCoV-HKU1 cause annual wintertime outbreaks of respiratory illness in temperate regions (10, 11), suggesting that wintertime climate and host behaviors may facilitate transmission, as is true for influenza (12–14). Immunity to HCoV-OC43 and HCoV-HKU1 appears to wane appreciably within one year (15), while SARS-CoV-1 infection can induce longer-lasting immunity (16). The betacoronaviruses can induce immune responses against one another: SARS-CoV-1 infection can generate neutralizing antibodies against HCoV-OC43 (16) and HCoV-OC43 infection can generate cross-reactive antibodies against SARS-CoV-1 (17). While investigations into the spectrum of illness caused by SARS-CoV-2 are ongoing, recent evidence indicates the majority of cases experience mild to moderate illness with more limited occurrence of severe lower respiratory infection (18). Current COVID-19 case fatality rates are estimated to lie between 0.6% and 3.5% (19, 20), suggesting lower severity than SARS-CoV-1 and MERS but higher severity than HCoV-OC43 and HCoV-HKU1. The high infectiousness near the start of often mild symptoms makes SARS-CoV-2 considerably harder to control with case-based interventions such as intensive testing, isolation and tracing, compared to SARS-CoV-1 and MERS coronaviruses (21).

Intensive testing and case-based interventions have so far formed the centerpiece of control efforts in some places, such as Singapore and Hong Kong (22). Many other countries are adopting measures termed “social distancing” or “physical distancing,” closing schools and workplaces and limiting the sizes of gatherings. The goal of these strategies is to reduce the peak intensity of the epidemic (“flatten the curve”) (22), reducing the risk of overwhelming health systems and buying time to develop treatments and vaccines. For social distancing to have reversed the epidemic in China, the effective reproduction number must have declined by at least 50-60%, assuming a baseline R0 between 2 and 2.5 (22). Through intensive control measures, Shenzhen was able to reduce the effective reproduction number by an estimated 85% (23). However, it is unclear how well these declines in R0 might generalize to other settings: recent data from Seattle suggests that the basic reproduction number has only declined to about 1.4, or by about 30-45% assuming a baseline R0 between 2 and 2.5 (24). Furthermore, social distancing measures may need to last for months to effectively control transmission and mitigate the possibility of resurgence (25).

A key metric for the success of social distancing interventions is whether critical care capacities are exceeded. Modeling studies (26) and experience from the Wuhan outbreak (2) indicate that critical care capacities even in high-income countries can be exceeded many times over if distancing measures are not implemented quickly or strongly enough. To alleviate these problems, approaches to increase critical care capacity have included rapid construction or repurposing of hospital facilities and consideration of increased manufacturing and distribution of ventilators (27–30). Treatments that reduce the proportion of infections that lead to severe illness could have a similar effect of reducing burden on healthcare systems.

This paper identifies viral, environmental, and immunologic factors which in combination will determine the dynamics of SARS-CoV-2. We integrate our findings in a mathematical model to project potential scenarios for SARS-CoV-2 transmission through the pandemic and post-pandemic periods and identify key data still needed to determine which scenarios are likely to play out. Then, using the model, we assess the duration and intensity of social distancing measures that might be needed to maintain control of SARS-CoV-2 in the coming months under both existing and expanded critical care capacities.

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14 April 2020

Stephen M. Kissler, Christine Tedijanto, Edward Goldstein, Yonatan H. Grad, Marc Lipsitch

https://science.sciencemag.org/content/early/2020/04/14/science.abb5793.full