Insights into COVID-19 epidemiology and control from temporal changes in serial interval distributions in Hong Kong

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to predict the effective reproductive number "Rt", a measure of transmissibility. However, serial interval distributions may change as an epidemic progresses rather than remaining constant. Here we show that serial intervals in Hong Kong varied over time, closely associated with the temporal variation in COVID-19 case profiles and public health and social measures that were implemented in response to surges in community transmission. Quantification of the variation over time in serial intervals led to improved estimation of Rt, and provided additional insights into the impact of public health measures on transmission of infections. One-Sentence SummaryReal-time estimates of serial interval distributions can improve assessment of COVID-19 transmission dynamics and control.

Inferring time-varying generation time, serial interval and incubation period distributions for COVID-19

BackgroundThe generation time distribution, reflecting the time between successive infections in transmission chains, is one of the fundamental epidemiological parameters for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution, reflecting the time between illness onsets of infector and infectee. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. MethodsWe analyzed data on observed incubation period and serial interval distributions in China, during January and February 2020, under different sampling approaches, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures. ResultsWe analyzed data on a total of 2989 confirmed cases for COVID-19 during January 1 to February 29, 2020 in Mainland China. During the study period, the empirical forward serial interval decreased from a mean of 8.90 days to 2.68 days. The estimated mean backward incubation period of infectors increased from 3.77 days to 9.61 days, and the mean forward incubation period of infectees also increased from 5.39 days to 7.21 days. The estimated mean forward generation time decreased from 7.27 days (95% confidence interval: 6.42, 8.07) to 4.21 days (95% confidence interval: 3.70, 4.74) days by January 29. We used simulations to examine the sensitivity of our modelling approach to a number of assumptions and alternative dynamics. ConclusionsThe proposed method can provide more reliable estimation of the temporal variation in the generation time distribution, enabling proper assessment of transmission dynamics.

The risk of SARS-CoV-2 Omicron variant emergence in low and middle-income countries (LMICs)

We estimated the probability of undetected emergence of the SARS-CoV-2 Omicron variant in 25 low and middle-income countries (LMICs) prior to December 5, 2021. In nine countries, the risk exceeds 50%; in Turkey, Pakistan and the Philippines, it exceeds 99%. Risks are generally lower in the Americas than Europe or Asia.

Superspreading of SARS-CoV-2 infections: A Systematic Review and Meta-analysis

Superspreading in transmission is a feature of SARS-CoV-2 transmission. We conducted a systematic review and meta-analysis on globally reported dispersion parameters of SARS-CoV-2. The pooled estimate was 0.55 (95% CI: 0.30, 0.79). The study location and method were found to be important drivers for its diversity.

International risk of SARS-CoV-2 Omicron variant importations originating in South Africa

Omicron, a fast-spreading SARS-CoV-2 variant of concern reported to the World Health Organization on November 24, 2021, has raised international alarm. We estimated there is at least 50% chance that Omicron had been introduced by travelers from South Africa into all of the 30 countries studied by November 27, 2021.

SARS-CoV-2 Transmission Potential and Policy Changes in South Carolina, February 2020 - January 2021

IntroductionWe aimed to examine how public health policies influenced the dynamics of COVID-19 time-varying reproductive number (Rt) in South Carolina from February 26, 2020 to January 1, 2021. MethodsCOVID-19 case series (March 6, 2020 - January 10, 2021) were shifted by 9 days to approximate the infection date. We analyzed the effects of state and county policies on Rt using EpiEstim. We performed linear regression to evaluate if per-capita cumulative case count varies across counties with different population size. ResultsRt shifted from 2-3 in March to <1 during April and May. Rt rose over the summer and stayed between 1.4 and 0.7. The introduction of statewide mask mandates was associated with a decline in Rt (-15.3%; 95% CrI, -13.6%, -16.8%), and school re-opening, an increase by 12.3% (95% CrI, 10.1%, 14.4%). Less densely populated counties had higher attack rate (p<0.0001). ConclusionThe Rt dynamics over time indicated that public health interventions substantially slowed COVID-19 transmission in South Carolina, while their relaxation may have promoted further transmission. Policies encouraging people to stay home, such as closing non-essential businesses, were associated with Rt reduction, while policies that encouraged more movement, such as re-opening schools, were associated with Rt increase.

The impacts of COVID-19 vaccine timing, number of doses, and risk prioritization on mortality in the US

As COVID-19 vaccination begins worldwide, policymakers face critical trade-offs. Using a mathematical model of COVID-19 transmission, we find that timing of the rollout is expected to have a substantially greater impact on mortality than risk-based prioritization and uptake and that prioritizing first doses over second doses may be life saving.

International risk of the new variant COVID-19 importations originating in the United Kingdom

A fast-spreading SARS-CoV-2 variant identified in the United Kingdom in December 2020 has raised international alarm. We estimate that, in all 15 countries analyzed, there is at least a 50% chance the variant was imported by travelers from the United Kingdom by December 7th.

Projecting the combined healthcare burden of seasonal influenza and COVID-19

The overlapping 2020-2021 influenza season and COVID-19 pandemic may overwhelm hospitals throughout the Northern Hemisphere. Using a mathematical model, we project that COVID-19 burden will dwarf that of influenza. If non-pharmacological mitigation efforts fail, increasing influenza vaccination coverage by 30% points would avert 54 hospitalizations per 100,000 people.

Design of COVID-19 Staged Alert Systems to Ensure Healthcare Capacity with Minimal Closures

Community mitigation strategies to combat COVID-19, ranging from healthy hygiene to shelter-in-place orders, exact substantial socioeconomic costs. Judicious implementation and relaxation of restrictions amplify their public health benefits while reducing costs. We derive optimal strategies for toggling between mitigation stages using daily COVID-19 hospital admissions. With public compliance, the policy triggers ensure adequate intensive care unit capacity with high probability while minimizing the duration of strict mitigation measures. In comparison, we show that other sensible COVID-19 staging policies, including Frances ICU-based thresholds and a widely adopted indicator for reopening schools and businesses, require overly restrictive measures or trigger strict stages too late to avert catastrophic surges. As cities worldwide face future pandemic waves, our findings provide a robust strategy for tracking COVID-19 hospital admissions as an early indicator of hospital surges and enacting staged measures to ensure integrity of the health system, safety of the health workforce, and public confidence.

Projected COVID-19 epidemic in the United States in the context of the effectiveness of a potential vaccine and implications for social distancing and face mask use

BackgroundMultiple candidates of COVID-19 vaccines have entered Phase III clinical trials in the United States (US). There is growing optimism that social distancing restrictions and face mask requirements could be eased with widespread vaccine adoption soon. MethodsWe developed a dynamic compartmental model of COVID-19 transmission for the four most severely affected states (New York, Texas, Florida, and California). We evaluated the vaccine effectiveness and coverage required to suppress the COVID-19 epidemic in scenarios when social contact was to return to pre-pandemic levels and face mask use was reduced. Daily and cumulative COVID-19 infection and death cases were obtained from the Johns Hopkins University Coronavirus resource center and used for model calibration. ResultsWithout a vaccine, the spread of COVID-19 could be suppressed in these states by maintaining strict social distancing measures and face mask use levels. But relaxing social distancing restrictions to the pre-pandemic level without changing the current face mask use would lead to a new COVID-19 outbreak, resulting in 0.8-4 million infections and 15,000-240,000 deaths across these four states over the next 12 months. In this scenario, introducing a vaccine would partially offset this negative impact even if the vaccine effectiveness and coverage are relatively low. However, if face mask use is reduced by 50%, a vaccine that is only 50% effective (weak vaccine) would require coverage of 55-94% to suppress the epidemic in these states. A vaccine that is 80% effective (moderate vaccine) would only require 32-57% coverage to suppress the epidemic. In contrast, if face mask usage stops completely, a weak vaccine would not suppress the epidemic, and further major outbreaks would occur. A moderate vaccine with coverage of 48-78% or a strong vaccine (100% effective) with coverage of 33-58% would be required to suppress the epidemic. Delaying vaccination rollout for 1-2 months would not substantially alter the epidemic trend if the current interventions are maintained. ConclusionsThe degree to which the US population can relax social distancing restrictions and face mask use will depend greatly on the effectiveness and coverage of a potential COVID-19 vaccine if future epidemics are to be prevented. Only a highly effective vaccine will enable the US population to return to life as it was before the pandemic.

The impact of asymptomatic COVID-19 infections on future pandemic waves

Letter textThe prevalence of asymptomatic COVID-19 infections is largely unknown and may determine the course of future pandemic waves and the effectiveness of interventions. Using an epidemiological model fit to COVID-19 hospitalization counts from New York City, New York and Austin, Texas, we found that the undocumented attack rate in the first pandemic wave depends on the proportion of asymptomatic infections but not on the infectiousness of such individuals. Based on a recent report that 22.7% of New Yorkers are seropositive for SARS-CoV-2, we estimate that 56% (95% CI: 53-59%) of COVID-19 infections are asymptomatic. Given uncertainty in the case hospitalization rate, however, the asymptomatic proportion could be as low as 20% or as high as 80%. We find that at most 1.26% of the Austin population was infected by April 27, 2020 and conclude that immunity from undetected infections is unlikely to slow future pandemic spread in most US cities in the summer of 2020.

CoVID-19 in Singapore: Impact of Contact Tracing and Self-awareness on Healthcare Demand

BackgroundA great concern around the globe now is to mitigate the COVID-19 pandemic via contact tracing. Analyzing the control strategies during the first five months of 2020 in Singapore is important to estimate the effectiveness of contacting tracing measures. MethodsWe developed a mathematical model to simulate the COVID-19 epidemic in Singapore, with local cases stratified into 5 categories according to the conditions of contact tracing and self-awareness. Key parameters of each category were estimated from local surveillance data. We also simulated a set of possible scenarios to predict the effects of contact tracing and self-awareness for the following month. FindingsDuring January 23 - March 16, 2020, the success probabilities of contact tracing and self-awareness were estimated to be 31% (95% CI 28%-33%) and 54% (95% CI 51%-57%), respectively. During March 17 - April 7, 2020, several social distancing measures (e.g., limiting mass gathering) were introduced in Singapore, which, however, were estimated with minor contribution to reduce the non-tracing reproduction number per local case (R{iota},2). If contact tracing and self-awareness cannot be further improved, we predict that the COVID-19 epidemic will continue to spread in Singapore if R{iota},2 [≥] 1.5. ConclusionContact tracing and self-awareness can mitigate the COVID-19 transmission, and can be one of the key strategies to ensure a sustainable reopening after lifting the lockdown. SummaryWe evaluate the efficiency of contact tracing and self-awareness in Singapores early-stage control of COVID-19. Then use a branching model to simulate and evaluate the possible prospective outcomes of Singapores COVID-19 control in different scenarios.

Cocooning is essential to relaxing social distancing

As the first wave of COVID-19 recedes, policymakers are contemplating the relaxation of shelter-in-place orders. Using a model capturing high-risk populations and transmission rates estimated from hospitalization data, we find that postponing relaxation will only delay a second wave and cocooning vulnerable populations is needed to prevent overwhelming medical surges.

COVID-19: How to Relax Social Distancing If You Must

Following the April 16, 2020 release of the Opening Up America Again guidelines for relaxing COVID-19 social distancing policies, local leaders are concerned about future pandemic waves and lack robust strategies for tracking and suppressing transmission. Here, we present a framework for monitoring COVID-19 hospitalization data to project risks and trigger shelter-in-place orders to prevent overwhelming healthcare surges while minimizing the duration of costly lockdowns. Assuming the relaxation of social distancing increases the risk of infection ten-fold, the optimal strategy for Austin, Texas--the fastest-growing large city in the US--will trigger a total of 135 [90% prediction interval: 126-141] days of sheltering, allow schools to open in the fall, and result in an expected 2929 deaths [90% prediction interval: 2837-3026] by September 2021, which is 29% the annual mortality rate. In the months ahead, policy makers are likely to face difficult choices and the extent of public restraint and cocooning of vulnerable populations may save or cost thousands of lives.

Using the COVID-19 to influenza ratio to estimate the numbers of symptomatic COVID-19 cases in Wuhan prior to the lockdown

A recent study tested 45 throat swabs taken from adults over age 30 who sought outpatient care at one of two central Wuhan hospitals for influenza-like-illness between December 30, 2019 and January 19, 2020. Although none were confirmed COVID-19 cases, nine retrospectively tested positive for the virus. Using the fact that Wuhan has 393 other hospitals, we extrapolate the total number of undetected cases of symptomatic COVID-19 in adults during this period. we estimate that there were 5,558 [95% CI: 2,761-9,864] adults with symptomatic COVID-19 infections in Wuhan between December 30th and January 19th, 2020.

COVID-19 serial interval estimates based on confirmed cases in public reports from 86 Chinese cities

As a novel coronavirus (COVID-19) continues to spread widely and claim lives worldwide, its transmission characteristics remain uncertain. Here, we present and analyze the serial intervals-the time period between the onset of symptoms in an index (infector) case and the onset of symptoms in a secondary (infectee) case-of 339 confirmed cases of COVID-19 identified from 264 cities in mainland China prior to February 19, 2020. Here, we provide the complete dataset in both English and Chinese to support further COVID-19 research and modeling efforts.

Proactive social distancing mitigates COVID-19 outbreaks within a month across 58 mainland China cities

In early 2020, cities across China enacted strict social distancing measures to contain emerging coronavirus (COVID-19) outbreaks. We estimated the speed with which these measures contained community transmission in each of 58 Chinese cities. On average, containment was achieved 7.83 days (SD 6.79 days) after the implementation of social distancing interventions, with an average reduction in the reproduction number (Rt) of 54.3% (SD 17.6%) over that time period. A single day delay in the implementation of social distancing led to a 2.41 (95% CI: 0.97, 3.86) day delay in containment. Swift social distancing interventions may thus achieve rapid containment of newly emerging COVID-19 outbreaks.

Impact of Social Distancing Measures on COVID-19 Healthcare Demand in Central Texas

BackgroundA novel coronavirus (SARS-CoV-2) emerged in Wuhan, China in late 2019 and rapidly spread worldwide. In the absence of effective antiviral drugs and vaccines, well-targeted social distancing measures are essential for mitigating the COVID-19 pandemic, reducing strain on local health systems, and preventing mortality. Here, we provide a quantitative assessment of the efficacy of social distancing to slow COVID-19 transmission and reduce hospital surge, depending on the timing and extent of the measures imposed for a metropolitan region and its health care systems. Methods and FindingsWe built a granular mathematical model of COVID-19 transmission that incorporated age-specific and risk-stratified heterogeneity, estimates for the transmission, and severity of COVID-19 using current best evidence. We performed thousands of stochastic simulations of COVID-19 transmission in the Austin-Round Rock Metropolitan Area to project the impact of school closures coupled with social distancing measures that were estimated to reduce non-household contacts by 0%, 25%, 50%, 75% or 90%. We compare early versus late implementation and estimate the number of COVID-19 hospitalizations, ICU patients, ventilator needs and deaths through mid-August, 2020. We queried local emergency services and hospital systems to estimate total hospital bed, ICU, and ventilator capacity for the region. We expected COVID-19 hospital beds and ICU requirements would surpass local capacity by mid-May if no intervention was taken. Assuming a four-day epidemic doubling time, school closures alone would be expected to reduce peak hospitalizations by only 18% and cumulative deaths by less than 3%. Immediate social distancing measures that reduced non-household contacts by over 75%, such as stay-at-home orders and closing of non-essential businesses, would be required to ensure that COVID-19 cases do not overwhelm local hospital surge capacity. Peak ICU bed demand prior to mid August 2020 would be expected to be reduced from 2,121 (95% CI: 2,018-2,208) with no intervention to 698 (95% CI: 204-1,100) with 75% social distancing and 136 (95% CI: 38-308) with 90% social distancing; current ICU bed capacity was estimated at 680. A two-week delay in implementation of such measures is projected to accelerate a local ICU bed shortage by four weeks. ConclusionsSchool closures alone hardly impact the epidemic curve. Immediate social distancing measures that reduce non-household contacts by over 75% were required to ensure that COVID-19 cases do not overwhelm local hospital surge capacity. These findings helped inform the Stay Home-Work Safe order enacted by the city of Austin, Texas on March 24, 2020 as a means of mitigating the emerging COVID-19 epidemic.

Hundreds of severe pediatric COVID-19 infections in Wuhan prior to the lockdown

Before January 22, 2020, only one pediatric case of COVID-19 was reported in mainland China1,2. However, a retrospective surveillance study3 identified six children who had been hospitalized for COVID-19 in one of three central Wuhan hospitals between January 7th and January 15th. Given that Wuhan has over 395 other hospitals, there may have been far more severe pediatric cases than reported.