Although SSEs appear to be difficult to predict and therefore difficult to prevent, understanding the pathogen, host, environmental, and behavioral drivers of SSEs can inform strategies for SSE prevention and control (19,20) (Table). The potential impact of these factors has been analyzed (5). We summarize the evidence for multiple pathogens to facilitate a more generalized approach that can be applied to the current COVID-19 pandemic.

Pathogen-specific factors include binding sites (29), environmental persistence, virulence, and infectious dose. Strains of some organisms might be more readily transmissible than other strains of the same species (21,22). Mutation can potentially lead to increased infectivity (6); one preliminary report suggested that SARS-CoV-2 might have 2 distinct genetic subtypes, with the less lethal form becoming more dominant as a result of treating and isolating infected persons (30). Monitoring for genetic adaptation, both by whole-genome sequencing and epidemiologic investigation, will determine whether transmissibility of SARS-CoV-2 is evolving and whether variants of the virus are more readily transmitted.

Host factors include duration of infection (prolonged carriage), location and burden of infection (e.g., laryngeal or cavitary tuberculosis), and symptomatology (e.g., transmission of influenza during the prodromal phase) (23). All SARS superspreaders were symptomatic. The potential for and extent of transmission of COVID-19 from asymptomatic infected persons has not yet been fully characterized, although probable asymptomatic transmission has been documented in at least 1 family cluster (31). Epidemiologic analysis is required to understand the proportion of COVID-19 transmission which occurs before symptom onset, whether children are effective transmitters, and to identify host factors that might be associated with increased infectivity (32).

Environmental factors include population density and the availability and use of infection prevention and control measures in healthcare facilities. SARS and MERS had relatively low rates of person-to-person transmission but caused explosive outbreaks in healthcare settings (28). Rapid person-to-person transmission of COVID-19 appears likely to have occurred in healthcare settings, on a cruise ship, and in a church (3). In a study of 110 case-patients from 11 clusters in Japan, all clusters were associated with closed environments, including fitness centers, shared eating environments, and hospitals; the odds for transmission from a primary case-patient were 18.7 times higher than in open-air environments (H. Nishiura et al., unpub. data, https://doi.org/10.1101/2020.02.28.20029272). SARS-CoV-2 is present in stool (33); ensuring cleanliness of toilets and other potentially contaminated surfaces is needed, and measures to prevent aerosolization from plumbing, as might have occurred in the Amoy Garden outbreak of SARS (24), might need to be implemented. Evidence of environmental contamination by SARS-CoV-2 through respiratory droplets and fecal shedding highlights the need for effective decontamination efforts and strict adherence to environmental hygiene, which are pertinent to prevention and control of transmission, including SSEs (34).

Behavioral factors include cough hygiene, social customs, health-seeking behavior, and adherence to public health guidance. The risk for SSEs varies widely on the basis of cultural and socioeconomic context. In Sierra Leone, 1 traditional funeral was associated with 28 laboratory-confirmed cases of Ebola (26,35). Perceptions of risk can influence behavior and the likelihood of SSEs. Underestimation of risk in healthcare facilities resulted in transmission that prolonged the Ebola outbreak in Guinea (27). During the MERS outbreak in South Korea, doctor shopping (visiting multiple healthcare facilities after symptoms developed) was associated with SSEs (36). For control of COVID-19, behavioral recommendations for the general population to wash hands, cover coughs, and minimize exposing others, as well as rigorous infection control for healthcare workers, are needed.

Response factors include the timely and effective implementation of prevention and control measures within the community and in healthcare settings. These factors can reduce outbreak duration and decrease the reproductive number, thereby reducing the number of persons infected. Because delay of diagnosis is the most common cause of SSEs (16), timeliness is critical to prevent or limit their extent (20). Rapid identification and isolation of cases will reduce transmission; where necessary, large-scale NPIs should also be implemented in affected areas within 1 week (37). Effective case isolation and contact tracing might be sufficient to control a cluster of COVID-19, but the probability of control will decrease with delays in patient isolation from symptom onset (38).

SSE prevention and mitigation depends, first and foremost, on quickly recognizing and understanding these events. This recognition and understanding enables implementation of control measures specific to the incident and identification of measures, which can reduce the risk for future SSEs. During the SARS epidemic, rapid quarantine and isolation reduced outbreak extent and speed (19), and the lack of early detection was the primary cause of a hospital MERS outbreak in South Korea (39). An analysis of available data from Hong Kong, Vietnam, Singapore, and Canada found that delaying SARS control measures by just a week could have tripled the size of the epidemic (7). A modeling study of control interventions and SSEs in South Korea found that timely interventions (within 1 week), including a government announcement of affected hospitals, reduced the size and duration of MERS transmission (28).

Healthcare facilities are critical for prevention and control of SSEs. Targeted control measures include rapid identification and isolation of all potentially infectious patients, including a high index of suspicion for transmissible diseases, and implementation of universal infection control procedures in all areas of all facilities (20,40). Because individual superspreaders can only be identified retrospectively, universal implementation of triage procedures, rapid diagnosis and isolation, administrative controls (e.g., flow patterns and procedures for patients, visitors, and staff), and engineering controls (e.g., isolation rooms, partitions to protect against respiratory droplets, ventilation systems) are all necessary (28). Meticulous infection control is especially needed when performing procedures such as bronchoscopy, intubation, suctioning, sputum induction, and nebulizer therapies, which can enable what would normally be a droplet-transmitted infection to become aerosolized and therefore able to be more widely disseminated. If these types of procedures are needed, they should be performed by using strict infection control procedures and, when possible, in airborne infection isolation units.

SSEs in healthcare settings can be associated with increased illness and death because many infections occur among patients with underlying conditions, which can delay diagnosis and exacerbate pathologic changes (41,42). Most tuberculosis is spread by patients who have not yet been given a diagnosis, rather than by failure to effectively isolate these patients (43). Risk factors for SSEs of SARS among 86 wards in Guangzhou, China, and 38 wards in Hong Kong were related to inadequate infection prevention and control, including insufficient availability of washing and changing facilities for staff, performing resuscitation on the ward, staff working while experiencing symptoms, and use of oxygen therapy or positive pressure ventilation (25). One patient in China who had only abdominal symptoms was not initially suspected of having COVID-19 and was admitted to a surgical ward; >10 healthcare workers and >4 patients were presumed to have been infected by this patient (3). It is essential that healthcare facilities implement infection control guidelines for COVID-19 rigorously. It is also essential that any nosocomial transmission is analyzed to identify the modes of spread, which will inform best strategies for prevention.

SSEs also occur in settings other than healthcare settings (44). The SARS outbreak in Hong Kong was characterized by 2 SSEs responsible for >400 infections (45); 1 guest at the Metropole Hotel was the index case for 4 national and international clusters (46). Community-wide NPIs, including risk communication to the public on social distancing, hand and respiratory hygiene, and criteria for either self-isolation or safer presentation to the hospital, can limit community transmission. During the SARS outbreak, effective communication appears to have reduced time from symptom onset to hospital admission and decreased the number of persons with whom patients had contact before isolation (25). The combination of facility-based and population-based interventions ended SARS transmission (19,47).

A study modeling the impact of interventions in Wuhan found that, although early identification and isolation reduced the number of infections somewhat, integrated implementation of NPIs decreased the number of cases rapidly and substantially and drove the reproductive number to <1 (C. Wang et al., unpub. data, https://doi.org/10.1101/2020.03.03.20030593). If NPIs had been implemented 2 weeks earlier, an estimated 86% of cases might have been prevented (48). For COVID-19, broad infection prevention and control measures include cough and hand hygiene, self-isolation by staying home if sick, and avoiding infection during care-seeking and caregiving.

COVID-19 has already killed more persons than SARS and MERS combined. Both of these coronavirus infections were fueled by SSEs. Understanding transmission dynamics associated with SSEs and their control during other coronavirus outbreaks can help inform current public health approaches to SARS-CoV-2. Anticipated heterogeneity in transmission should be used to plan disease control programs and risk-stratify populations for public health interventions. Countries should develop and implement protocols for implementation of rapid identification, diagnosis, and isolation of patients; effective infection prevention and control practices in healthcare facilities; and timely and relevant risk communication. Such measures can mitigate the impact of SSEs, which have been major drivers of recent epidemics.

Because delay in diagnosis and failure to rapidly implement isolation and response measures have fueled previous SSEs, countries should have plans and operational capacities in place during the containment phase of the response for immediate investigation and implementation of control measures. During the later mitigation phase, when surveillance and laboratory resources are limited, surveillance and focused response efforts should prioritize environments and settings at high risk for SSEs, including closed environments such as healthcare facilities, nursing homes, prisons, homeless shelters, schools, and sites of mass gatherings while community-wide NPIs are implemented more broadly.

Targeted and rapidly implemented public health interventions to prevent and mitigate SSEs are critical for early interruption of transmission during the containment phase and to reduce the effect on the disruption of healthcare services and society during the mitigation phase. Because of the societal and cultural underpinnings of behavioral and environmental factors including the local acceptability of adoption of NPIs, early engagement of communities, including an in-depth understanding of knowledge, attitudes, and practices relevant to the pandemic will be critical to response efforts during all phases.