Correlation between times to SARS-CoV-2 symptom onset and secondary transmission undermines epidemic control efforts.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infections have been associated with substantial presymptomatic transmission, which occurs when the generation interval-the time between infection of an individual with a pathogen and transmission of the pathogen to another individual-is shorter than the incubation period-the time between infection and symptom onset. We collected a dataset of 257 SARS-CoV-2 transmission pairs in Japan during 2020 and jointly estimated the mean incubation period of infectors (4.8 days, 95 % CrI: 4.4-5.1 days), mean generation interval to when they infect others (4.3 days, 95 % credible interval [CrI]: 4.0-4.7 days), and the correlation (Kendall's tau: 0.5, 95 % CrI: 0.4-0.6) between these two epidemiological parameters. Our finding of a positive correlation and mean generation interval shorter than the mean infector incubation period indicates ample infectiousness before symptom onset and suggests that reliance on isolation of symptomatic COVID-19 cases as a focal point of control efforts is insufficient to address the challenges posed by SARS-CoV-2 transmission dynamics.

Transmission Dynamics and Effectiveness of Control Measures during COVID-19 Surge, Taiwan, April-August 2021.

An unprecedented surge of COVID-19 cases in Taiwan in May 2021 led the government to implement strict nationwide control measures beginning May 15. During the surge, the government was able to bring the epidemic under control without a complete lockdown despite the cumulative case count reaching >14,400 and >780 deaths. We investigated the effectiveness of the public health and social measures instituted by the Taiwan government by quantifying the change in the effective reproduction number, which is a summary measure of the ability of the pathogen to spread through the population. The control measures that were instituted reduced the effective reproduction number from 2.0-3.3 to 0.6-0.7. This decrease was correlated with changes in mobility patterns in Taiwan, demonstrating that public compliance, active case finding, and contact tracing were effective measures in preventing further spread of the disease.

Phenomenological and mechanistic models for predicting early transmission data of COVID-19.

Forecasting future epidemics helps inform policy decisions regarding interventions. During the early coronavirus disease 2019 epidemic period in January-February 2020, limited information was available, and it was too challenging to build detailed mechanistic models reflecting population behavior. This study compared the performance of phenomenological and mechanistic models for forecasting epidemics. For the former, we employed the Richards model and the approximate solution of the susceptible-infected-recovered (SIR) model. For the latter, we examined the exponential growth (with lockdown) model and SIR model with lockdown. The phenomenological models yielded higher root mean square error (RMSE) values than the mechanistic models. When using the numbers from reported data for February 1 and 5, the Richards model had the highest RMSE, whereas when using the February 9 data, the SIR approximation model was the highest. The exponential model with a lockdown effect had the lowest RMSE, except when using the February 9 data. Once interventions or other factors that influence transmission patterns are identified, they should be additionally taken into account to improve forecasting.

Age dependence of the natural history of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): an analysis of Diamond Princess data.

BACKGROUND: Following an outbreak of coronavirus disease 2019 (COVID-19) on the cruise ship Diamond Princess, passengers and crew were followed-up to determine prognosis. This study examined the epidemiological determinants of COVID-19 natural history using these follow-up data. METHODS: Infection status, diagnosis, clinical symptoms and prognosis were analysed for all passengers and crew members on the Diamond Princess. In addition, the risk of infection associated with exposure within cabin rooms, as well as the risks of various clinical manifestations of disease, along with their epidemiological determinants, were analysed. RESULTS: The adjusted odds ratio (aOR) of infection for individuals tested by polymerase chain reaction on or after 12 February 2020 compared with individuals tested before this date was 0.53 [95% confidence interval (CI) 0.39-0.72], reflecting decreased transmission during onboard quarantine. Among infected individuals, older age was associated with elevated odds of symptomatic illness (aOR 1.01, 95% CI 1.00-1.02), severe disease (aOR 1.08, 95% CI 1.05-1.12) and death (aOR 1.12, 95% CI 1.05-1.21). CONCLUSIONS: Severe COVID-19 disease, death and symptomatic illness were more frequent among older individuals on the Diamond Princess. Older elderly cases (age ≥80 years) had the highest risks of severe disease and death. Inter-room transmission was prevented successfully by the onboard quarantine.

Not all fun and games: Potential incidence of SARS-CoV-2 infections during the Tokyo 2020 Olympic Games.

The Tokyo 2020 Olympic and Paralympic Games represent the most diverse international mass gathering event held since the start of the coronavirus disease 2019 (COVID-19) pandemic. Postponed to summer 2021, the rescheduled Games were set to be held amidst what would become the highest-ever levels of COVID-19 transmission in the host city of Tokyo. At the same time, the Delta variant of concern was gaining traction as the dominant viral strain and Japan had yet to exceed fifteen percent of its population fully vaccinated against COVID-19. To quantify the potential number of secondary cases that might arise during the Olympic Games, we performed a scenario analysis using a multitype branching process model. We considered the different contributions to transmission of Games accredited individuals, the general Tokyo population, and domestic spectators. In doing so, we demonstrate how transmission might evolve in these different groups over time, cautioning against any loosening of infection prevention protocols and supporting the decision to ban all spectators. If prevention measures were well observed, we estimated that the number of new cases among Games accredited individuals would approach zero by the end of the Games. However, if transmission was not controlled our model indicated hundreds of Games accredited individuals would become infected and daily incidence in Tokyo would reach upwards of 4,000 cases. Had domestic spectators been allowed (at 50% venue capacity), we estimated that over 250 spectators might have arrived infected to Tokyo venues, potentially generating more than 300 additional secondary infections while in Tokyo/at the Games. We also found the number of cases with infection directly attributable to hypothetical exposure during the Games was highly sensitive to the local epidemic dynamics. Therefore, reducing and maintaining transmission levels below epidemic levels using public health measures would be necessary to prevent cross-group transmission.

Estimation of the Actual Incidence of Coronavirus Disease (COVID-19) in Emergent Hotspots: The Example of Hokkaido, Japan during February-March 2020.

Following the first report of the coronavirus disease 2019 (COVID-19) in Sapporo city, Hokkaido Prefecture, Japan, on 14 February 2020, a surge of cases was observed in Hokkaido during February and March. As of 6 March, 90 cases were diagnosed in Hokkaido. Unfortunately, many infected persons may not have been recognized due to having mild or no symptoms during the initial months of the outbreak. We therefore aimed to predict the actual number of COVID-19 cases in (i) Hokkaido Prefecture and (ii) Sapporo city using data on cases diagnosed outside these areas. Two statistical frameworks involving a balance equation and an extrapolated linear regression model with a negative binomial link were used for deriving both estimates, respectively. The estimated cumulative incidence in Hokkaido as of 27 February was 2,297 cases (95% confidence interval (CI): 382-7091) based on data on travelers outbound from Hokkaido. The cumulative incidence in Sapporo city as of 28 February was estimated at 2233 cases (95% CI: 0-4893) based on the count of confirmed cases within Hokkaido. Both approaches resulted in similar estimates, indicating a higher incidence of infections in Hokkaido than were detected by the surveillance system. This quantification of the gap between detected and estimated cases helped to inform the public health response at the beginning of the pandemic and provided insight into the possible scope of undetected transmission for future assessments.

Localized end-of-outbreak determination for coronavirus disease 2019 (COVID-19): examples from clusters in Japan.

OBJECTIVES: End-of-outbreak declarations are an important component of outbreak response because they indicate that public health and social interventions may be relaxed or lapsed. Our study aimed to assess end-of-outbreak probabilities for clusters of coronavirus disease 2019 (COVID-19) cases detected during the first wave of the COVID-19 pandemic in Japan. METHODS: A statistical model for end-of-outbreak determination, which accounted for reporting delays for new cases, was computed. Four clusters, representing different social contexts and time points during the first wave of the epidemic, were selected and their end-of-outbreak probabilities were evaluated. RESULTS: The speed of end-of-outbreak determination was most closely tied to outbreak size. Notably, accounting underascertainment of cases led to later end-of-outbreak determinations. In addition, end-of-outbreak determination was closely related to estimates of case dispersionk and the effective reproduction number Re. Increasing local transmission (Re>1) leads to greater uncertainty in the probability estimates. CONCLUSIONS: When public health measures are effective, lowerRe (less transmission on average) and larger k (lower risk of superspreading) will be in effect, and end-of-outbreak determinations can be declared with greater confidence. The application of end-of-outbreak probabilities can help distinguish between local extinction and low levels of transmission, and communicating these end-of-outbreak probabilities can help inform public health decision making with regard to the appropriate use of resources.

Containment, Contact Tracing and Asymptomatic Transmission of Novel Coronavirus Disease (COVID-19): A Modelling Study.

When a novel infectious disease emerges, enhanced contact tracing and isolation are implemented to prevent a major epidemic, and indeed, they have been successful for the control of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which have been greatly reduced without causing a global pandemic. Considering that asymptomatic and pre-symptomatic infections are substantial for the novel coronavirus disease (COVID-19), the feasibility of preventing the major epidemic has been questioned. Using a two-type branching process model, the present study assesses the feasibility of containing COVID-19 by computing the probability of a major epidemic. We show that if there is a substantial number of asymptomatic transmissions, cutting chains of transmission by means of contact tracing and case isolation would be very challenging without additional interventions, and in particular, untraced cases contribute to lowering the feasibility of containment. Even if isolation of symptomatic cases is conducted swiftly after symptom onset, only secondary transmissions after the symptom onset can be prevented.

Communicating the Risk of Death from Novel Coronavirus Disease (COVID-19).

To understand the severity of infection for a given disease, it is common epidemiological practice to estimate the case fatality risk, defined as the risk of death among cases. However, there are three technical obstacles that should be addressed to appropriately measure this risk. First, division of the cumulative number of deaths by that of cases tends to underestimate the actual risk because deaths that will occur have not yet observed, and so the delay in time from illness onset to death must be addressed. Second, the observed dataset of reported cases represents only a proportion of all infected individuals and there can be a substantial number of asymptomatic and mildly infected individuals who are never diagnosed. Third, ascertainment bias and risk of death among all those infected would be smaller when estimated using shorter virus detection windows and less sensitive diagnostic laboratory tests. In the ongoing COVID-19 epidemic, health authorities must cope with the uncertainty in the risk of death from COVID-19, and high-risk individuals should be identified using approaches that can address the abovementioned three problems. Although COVID-19 involves mostly mild infections among the majority of the general population, the risk of death among young adults is higher than that of seasonal influenza, and elderly with underlying comorbidities require additional care.

Serial interval of novel coronavirus (COVID-19) infections.

OBJECTIVE: To estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs. METHODS: We collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We subjectively ranked the credibility of the data and performed analyses on both the full dataset (n = 28) and a subset of pairs with highest certainty in reporting (n = 18). In addition, we adjust for right truncation of the data as the epidemic is still in its growth phase. RESULTS: Accounting for right truncation and analyzing all pairs, we estimated the median serial interval at 4.0 days (95% credible interval [CrI]: 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI: 3.5, 5.9). CONCLUSIONS: The serial interval of COVID-19 is close to or shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset. The COVID-19 serial interval is also shorter than the serial interval of severe acute respiratory syndrome (SARS), indicating that calculations made using the SARS serial interval may introduce bias.

Epidemiological Identification of A Novel Pathogen in Real Time: Analysis of the Atypical Pneumonia Outbreak in Wuhan, China, 2019-2020.

Virological tests have now shown conclusively that a novel coronavirus is causing the 2019-2020 atypical pneumonia outbreak in Wuhan, China. We demonstrate that non-virological descriptive characteristics could have determined that the outbreak is caused by a novel pathogen in advance of virological testing. Characteristics of the ongoing outbreak were collected in real time from two medical social media sites. These were compared against characteristics of eleven pathogens that have previously caused cases of atypical pneumonia. The probability that the current outbreak is due to "Disease X" (i.e., previously unknown etiology) as opposed to one of the known pathogens was inferred, and this estimate was updated as the outbreak continued. The probability (expressed as a percentage) that Disease X is driving the outbreak was assessed as over 29% on 31 December 2019, one week before virus identification. After some specific pathogens were ruled out by laboratory tests on 5 January 2020, the inferred probability of Disease X was over 49%. We showed quantitatively that the emerging outbreak of atypical pneumonia cases is consistent with causation by a novel pathogen. The proposed approach, which uses only routinely observed non-virological data, can aid ongoing risk assessments in advance of virological test results becoming available.

Assessing the Impact of Reduced Travel on Exportation Dynamics of Novel Coronavirus Infection (COVID-19).

The impact of the drastic reduction in travel volume within mainland China in January and February 2020 was quantified with respect to reports of novel coronavirus (COVID-19) infections outside China. Data on confirmed cases diagnosed outside China were analyzed using statistical models to estimate the impact of travel reduction on three epidemiological outcome measures: (i) the number of exported cases, (ii) the probability of a major epidemic, and (iii) the time delay to a major epidemic. From 28 January to 7 February 2020, we estimated that 226 exported cases (95% confidence interval: 86,449) were prevented, corresponding to a 70.4% reduction in incidence compared to the counterfactual scenario. The reduced probability of a major epidemic ranged from 7% to 20% in Japan, which resulted in a median time delay to a major epidemic of two days. Depending on the scenario, the estimated delay may be less than one day. As the delay is small, the decision to control travel volume through restrictions on freedom of movement should be balanced between the resulting estimated epidemiological impact and predicted economic fallout.

The Rate of Underascertainment of Novel Coronavirus (2019-nCoV) Infection: Estimation Using Japanese Passengers Data on Evacuation Flights.

From 29 to 31 January 2020, a total of 565 Japanese citizens were evacuated from Wuhan, China on three chartered flights. All passengers were screened upon arrival in Japan for symptoms consistent with novel coronavirus (2019-nCoV) infection and tested for presence of the virus. Assuming that the mean detection window of the virus can be informed by the mean serial interval (estimated at 7.5 days), the ascertainment rate of infection was estimated at 9.2% (95% confidence interval: 5.0, 20.0). This indicates that the incidence of infection in Wuhan can be estimated at 20,767 infected individuals, including those with asymptomatic and mildly symptomatic infections. The infection fatality risk (IFR)-the actual risk of death among all infected individuals-is therefore 0.3% to 0.6%, which may be comparable to Asian influenza pandemic of 1957-1958.

The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020.

A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred.

Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data.

The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2-14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3-4 days without truncation and at 5-9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.

Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases.

The exported cases of 2019 novel coronavirus (COVID-19) infection that were confirmed outside China provide an opportunity to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in mainland China. Knowledge of the cCFR is critical to characterize the severity and understand the pandemic potential of COVID-19 in the early stage of the epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number-the average number of secondary cases generated by a single primary case in a naïve population. We modeled epidemic growth either from a single index case with illness onset on 8 December, 2019 (Scenario 1), or using the growth rate fitted along with the other parameters (Scenario 2) based on data from 20 exported cases reported by 24 January 2020. The cumulative incidence in China by 24 January was estimated at 6924 cases (95% confidence interval [CI]: 4885, 9211) and 19,289 cases (95% CI: 10,901, 30,158), respectively. The latest estimated values of the cCFR were 5.3% (95% CI: 3.5%, 7.5%) for Scenario 1 and 8.4% (95% CI: 5.3%, 12.3%) for Scenario 2. The basic reproduction number was estimated to be 2.1 (95% CI: 2.0, 2.2) and 3.2 (95% CI: 2.7, 3.7) for Scenarios 1 and 2, respectively. Based on these results, we argued that the current COVID-19 epidemic has a substantial potential for causing a pandemic. The proposed approach provides insights in early risk assessment using publicly available data.

Initial Cluster of Novel Coronavirus (2019-nCoV) Infections in Wuhan, China Is Consistent with Substantial Human-to-Human Transmission.

Reanalysis of the epidemic curve from the initial cluster of cases with novel coronavirus (2019-nCoV) in December 2019 indicates substantial human-to-human transmission. It is possible that the common exposure history at a seafood market in Wuhan originated from the human-to-human transmission events within the market, and the early, strong emphasis that market exposure indicated animal-to-human transmission was potentially the result of observer bias. To support the hypothesis of zoonotic origin of 2019-nCoV stemming from the Huanan seafood market, the index case should have had exposure history related to the market and the virus should have been identified from animals sold at the market. As these requirements remain unmet, zoonotic spillover at the market must not be overemphasized.