[Latent period and incubation period with associated factors of COVID-19 caused by Omicron variant].

Objective: To estimate the latent period and incubation period of Omicron variant infections and analyze associated factors. Methods: From January 1 to June 30, 2022, 467 infections and 335 symptomatic infections in five local Omicron variant outbreaks in China were selected as the study subjects. The latent period and incubation period were estimated by using log-normal distribution and gamma distribution models, and the associated factors were analyzed by using the accelerated failure time model (AFT). Results: The median (Q1, Q3) age of 467 Omicron infections including 253 males (54.18%) was 26 (20, 39) years old. There were 132 asymptomatic infections (28.27%) and 335 (71.73%) symptomatic infections. The mean latent period of 467 Omicron infections was 2.65 (95%CI: 2.53-2.78) days, and 98% of infections were positive for nucleic acid test within 6.37 (95%CI: 5.86-6.82) days after infection. The mean incubation period of 335 symptomatic infections was 3.40 (95%CI: 3.25-3.57) days, and 97% of them developed clinical symptoms within 6.80 (95%CI: 6.34-7.22) days after infection. The results of the AFT model analysis showed that compared with the group aged 18-49 years old, the latent period [exp(ß)=1.36 (95%CI: 1.16-1.60), P<0.001] and incubation period [exp(ß)=1.24 (95%CI: 1.07-1.45), P=0.006] of infections aged 0-17 years old were prolonged. The latent period [exp(ß)=1.38 (95%CI: 1.17-1.63), P<0.001] and the incubation period [exp(ß)=1.26 (95%CI: 1.06-1.48), P=0.007] of infections aged 50 years old and above were also prolonged. Conclusion: The latent period and incubation period of most Omicron infections are within 7 days, and age may be a influencing factor of the latent period and incubation period.

Estimate the incubation period of coronavirus 2019 (COVID-19).

COVID-19 is an infectious disease that presents unprecedented challenges to society. Accurately estimating the incubation period of the coronavirus is critical for effective prevention and control. However, the exact incubation period remains unclear, as COVID-19 symptoms can appear in as little as 2 days or as long as 14 days or more after exposure. Accurate estimation requires original chain-of-infection data, which may not be fully available from the original outbreak in Wuhan, China. In this study, we estimated the incubation period of COVID-19 by leveraging well-documented and epidemiologically informative chain-of-infection data collected from 10 regions outside the original Wuhan areas prior to February 10, 2020. We employed a proposed Monte Carlo simulation approach and nonparametric methods to estimate the incubation period of COVID-19. We also utilized manifold learning and related statistical analysis to uncover incubation relationships between different age and gender groups. Our findings revealed that the incubation period of COVID-19 did not follow general distributions such as lognormal, Weibull, or Gamma. Using proposed Monte Carlo simulations and nonparametric bootstrap methods, we estimated the mean and median incubation periods as 5.84 (95% CI, 5.42-6.25 days) and 5.01 days (95% CI 4.00-6.00 days), respectively. We also found that the incubation periods of groups with ages greater than or equal to 40 years and less than 40 years demonstrated a statistically significant difference. The former group had a longer incubation period and a larger variance than the latter, suggesting the need for different quarantine times or medical intervention strategies. Our machine-learning results further demonstrated that the two age groups were linearly separable, consistent with previous statistical analyses. Additionally, our results indicated that the incubation period difference between males and females was not statistically significant.

SARS-CoV-2 incubation period across variants of concern, individual factors, and circumstances of infection in France: a case series analysis from the ComCor study.

BACKGROUND: The incubation period of SARS-CoV-2 has been estimated for the known variants of concern. However, differences in study designs and settings make comparing variants difficult. We aimed to estimate the incubation period for each variant of concern compared with the historical strain within a unique and large study to identify individual factors and circumstances associated with its duration. METHODS: In this case series analysis, we included participants (aged ≥18 years) of the ComCor case-control study in France who had a SARS-CoV-2 diagnosis between Oct 27, 2020, and Feb 4, 2022. Eligible participants were those who had the historical strain or a variant of concern during a single encounter with a known index case who was symptomatic and for whom the incubation period could be established, those who reported doing a reverse-transcription-PCR (RT-PCR) test, and those who were symptomatic by study completion. Sociodemographic and clinical characteristics, exposure information, circumstances of infection, and COVID-19 vaccination details were obtained via an online questionnaire, and variants were established through variant typing after RT-PCR testing or by matching the time that a positive test was reported with the predominance of a specific variant. We used multivariable linear regression to identify factors associated with the duration of the incubation period (defined as the number of days from contact with the index case to symptom onset). FINDINGS: 20 413 participants were eligible for inclusion in this study. Mean incubation period varied across variants: 4·96 days (95% CI 4·90-5·02) for alpha (B.1.1.7), 5·18 days (4·93-5·43) for beta (B.1.351) and gamma (P.1), 4·43 days (4·36-4·49) for delta (B.1.617.2), and 3·61 days (3·55-3·68) for omicron (B.1.1.529) compared with 4·61 days (4·56-4·66) for the historical strain. Participants with omicron had a shorter incubation period than participants with the historical strain (-0·9 days, 95% CI -1·0 to -0·7). The incubation period increased with age (participants aged ≥70 years had an incubation period 0·4 days [0·2 to 0·6] longer than participants aged 18-29 years), in female participants (by 0·1 days, 0·0 to 0·2), and in those who wore a mask during contact with the index case (by 0·2 days, 0·1 to 0·4), and was reduced in those for whom the index case was symptomatic (-0·1 days, -0·2 to -0·1). These data were robust to sensitivity analyses correcting for an over-reporting of incubation periods of 7 days. INTERPRETATION: SARS-CoV-2 incubation period is notably reduced in omicron cases compared with all other variants of concern, in young people, after transmission from a symptomatic index case, after transmission to a maskless secondary case, and (to a lesser extent) in men. These findings can inform future COVID-19 contact-tracing strategies and modelling. FUNDING: Institut Pasteur, the French National Agency for AIDS Research-Emerging Infectious Diseases, Fondation de France, the INCEPTION project, and the Integrative Biology of Emerging Infectious Diseases project.

Serial Intervals and Incubation Periods of SARS-CoV-2 Omicron and Delta Variants, Singapore.

We compared serial intervals and incubation periods for SARS-CoV-2 Omicron BA.1 and BA.2 subvariants and Delta variants in Singapore. Median incubation period was 3 days for BA.1 versus 4 days for Delta. Serial interval was 2 days for BA.1 and 3 days for BA.2 but 4 days for Delta.

Comparing the incubation period, serial interval, and infectiousness profile between SARS-CoV-2 Omicron and Delta variants.

In January 2022, the SARS-CoV-2 Omicron variants initiated major outbreaks and dominated the transmissions in Hong Kong, displacing an earlier outbreak seeded by the Delta variants. To provide insight into the transmission potential of the emerging variants, we aimed to compare the epidemiological characteristics of the Omicron and Delta variants. We analyzed the line-list clinical and contact tracing data of the SARS-CoV-2 confirmed cases in Hong Kong. Transmission pairs were constructed based on the individual contact history. We fitted bias-controlled models to the data to estimate the serial interval, incubation period and infectiousness profile of the two variants. Viral load data were extracted and fitted to the random effect models to investigate the potential risk modifiers for the clinical viral shedding course. Totally 14 401 confirmed cases were reported between January 1 and February 15, 2022. The estimated mean serial interval (4.4 days vs. 5.8 days) and incubation period (3.4 days vs. 3.8 days) were shorter for the Omicron than the Delta variants. A larger proportion of presymptomatic transmission was observed for the Omicron (62%) compared to the Delta variants (48%). The Omicron cases had higher mean viral load over an infection course than the Delta cases, with the elder cases appearing more infectious than the younger cases for both variants. The epidemiological features of Omicron variants were likely an obstacle to contact tracing measures, imposed as a major intervention in settings like Hong Kong. Continuously monitoring the epidemiological feature for any emerging SARS-CoV-2 variants in the future is needed to assist officials in planning measures for COVID-19 control.

[Study of incubation period of infection with 2019-nCoV Omicron variant BA.5.1.3].

Objective: To study the incubation period of the infection with 2019-nCoV Omicron variant BA.5.1.3. Methods: Based on the epidemiological survey data of 315 COVID-19 cases and the characteristics of interval censored data structure, log-normal distribution and Gamma distribution were used to estimate the incubation. Bayes estimation was performed for the parameters of each distribution function using discrete time Markov chain Monte Carlo algorithm. Results: The mean age of the 315 COVID-19 cases was (42.01±16.54) years, and men accounted for 30.16%. A total of 156 cases with mean age of (41.65±16.32) years reported the times when symptoms occurred. The log-normal distribution and Gamma distribution indicated that the M (Q1, Q3) of the incubation period from exposure to symptom onset was 2.53 (1.86, 3.44) days and 2.64 (1.91, 3.52) days, respectively, and the M (Q1, Q3) of the incubation period from exposure to the first positive nucleic acid detection was 2.45 (1.76, 3.40) days and 2.57 (1.81, 3.52) days, respectively. Conclusions: The incubation period by Bayes estimation based on log-normal distribution and Gamma distribution, respectively, was similar to each other, and the best distribution of incubation period was Gamma distribution, the difference between the incubation period from exposure to the first positive nucleic acid detection and the incubation period from exposure to symptom onset was small. The median of incubation period of infection caused by Omicron variant BA.5.1.3 was shorter than those of previous Omicron variants.

SARS-CoV-2 Incubation Period during the Omicron BA.5-Dominant Period in Japan.

The mean virus incubation period during the SARS-CoV-2 Omicron BA.5-dominant period in Japan was 2.6 (95% CI 2.5-2.8) days, which was less than during the Delta-dominant period. Incubation period correlated with shared meals and adult infectors. A shorter incubation suggests a shorter quarantine period for BA.5 than for other variants.

Estimation of the incubation period and generation time of SARS-CoV-2 Alpha and Delta variants from contact tracing data.

Quantitative information on epidemiological quantities such as the incubation period and generation time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is scarce. We analysed a dataset collected during contact tracing activities in the province of Reggio Emilia, Italy, throughout 2021. We determined the distributions of the incubation period for the Alpha and Delta variants using information on negative polymerase chain reaction tests and the date of last exposure from 282 symptomatic cases. We estimated the distributions of the intrinsic generation time using a Bayesian inference approach applied to 9724 SARS-CoV-2 cases clustered in 3545 households where at least one secondary case was recorded. We estimated a mean incubation period of 4.9 days (95% credible intervals, CrI, 4.4-5.4) for Alpha and 4.5 days (95% CrI 4.0-5.0) for Delta. The intrinsic generation time was estimated to have a mean of 7.12 days (95% CrI 6.27-8.44) for Alpha and of 6.52 days (95% CrI 5.54-8.43) for Delta. The household serial interval was 2.43 days (95% CrI 2.29-2.58) for Alpha and 2.74 days (95% CrI 2.62-2.88) for Delta, and the estimated proportion of pre-symptomatic transmission was 48-51% for both variants. These results indicate limited differences in the incubation period and intrinsic generation time of SARS-CoV-2 variants Alpha and Delta compared to ancestral lineages.

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

The generation time distribution, reflecting the time between successive infections in transmission chains, is a key epidemiological parameter for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. We estimated incubation period and serial interval distributions using 629 transmission pairs reconstructed by investigating 2989 confirmed cases in China in January-February 2020, 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. We identified substantial reductions over time in the serial interval and generation time distributions. Our proposed method provides more reliable estimation of the temporal variation in the generation time distribution, improving assessment of transmission dynamics.

SARS-Cov-2 incubation period according to vaccination status during the fifth COVID-19 wave in a tertiary-care center in Spain: a cohort study.

BACKGROUND: The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period. METHODS: We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The distribution of the incubation period was estimated using the generalized odds-rate class of regression models. RESULTS: From 406 surveyed patients, 242 provided adequate information to be included in the analysis. The median incubation period was 2.8 days (95%CI: 2.5-3.1) and no differences between vaccinated and unvaccinated patients were found. Sex and age are neither shown not to be significantly related to the COVID-19 incubation time. CONCLUSIONS: Knowing the incubation period is crucial for controlling the spread of an infectious disease: decisions on the duration of the quarantine or on the periods of active monitoring of people who have been at high risk of exposure depend on the length of the incubation period. Furthermore, its probability distribution is a key element for predicting the prevalence and the incidence of the disease.

The Association Between Clinical Severity and Incubation Period of SARS-CoV-2 Delta Variants: Retrospective Observational Study.

BACKGROUND: As of August 25, 2021, Jiangsu province experienced the largest COVID-19 outbreak in eastern China that was seeded by SARS-CoV-2 Delta variants. As one of the key epidemiological parameters characterizing the transmission dynamics of COVID-19, the incubation period plays an essential role in informing public health measures for epidemic control. The incubation period of COVID-19 could vary by different age, sex, disease severity, and study settings. However, the impacts of these factors on the incubation period of Delta variants remains uninvestigated. OBJECTIVE: The objective of this study is to characterize the incubation period of the Delta variant using detailed contact tracing data. The effects of age, sex, and disease severity on the incubation period were investigated by multivariate regression analysis and subgroup analysis. METHODS: We extracted contact tracing data of 353 laboratory-confirmed cases of SARS-CoV-2 Delta variants' infection in Jiangsu province, China, from July to August 2021. The distribution of incubation period of Delta variants was estimated by using likelihood-based approach with adjustment for interval-censored observations. The effects of age, sex, and disease severity on the incubation period were expiated by using multivariate logistic regression model with interval censoring. RESULTS: The mean incubation period of the Delta variant was estimated at 6.64 days (95% credible interval: 6.27-7.00). We found that female cases and cases with severe symptoms had relatively longer mean incubation periods than male cases and those with nonsevere symptoms, respectively. One-day increase in the incubation period of Delta variants was associated with a weak decrease in the probability of having severe illness with an adjusted odds ratio of 0.88 (95% credible interval: 0.71-1.07). CONCLUSIONS: In this study, the incubation period was found to vary across different levels of sex, age, and disease severity of COVID-19. These findings provide additional information on the incubation period of Delta variants and highlight the importance of continuing surveillance and monitoring of the epidemiological characteristics of emerging SARS-CoV-2 variants as they evolve.

Incubation Period of COVID-19 Caused by Unique SARS-CoV-2 Strains: A Systematic Review and Meta-analysis.

Importance: Several studies were conducted to estimate the average incubation period of COVID-19; however, the incubation period of COVID-19 caused by different SARS-CoV-2 variants is not well described. Objective: To systematically assess the incubation period of COVID-19 and the incubation periods of COVID-19 caused by different SARS-CoV-2 variants in published studies. Data Sources: PubMed, EMBASE, and ScienceDirect were searched between December 1, 2019, and February 10, 2022. Study Selection: Original studies of the incubation period of COVID-19, defined as the time from infection to the onset of signs and symptoms. Data Extraction and Synthesis: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 3 reviewers independently extracted the data from the eligible studies in March 2022. The parameters, or sufficient information to facilitate calculation of those values, were derived from random-effects meta-analysis. Main Outcomes and Measures: The mean estimate of the incubation period and different SARS-CoV-2 strains. Results: A total of 142 studies with 8112 patients were included. The pooled incubation period was 6.57 days (95% CI, 6.26-6.88) and ranged from 1.80 to 18.87 days. The incubation period of COVID-19 caused by the Alpha, Beta, Delta, and Omicron variants were reported in 1 study (with 6374 patients), 1 study (10 patients), 6 studies (2368 patients) and 5 studies (829 patients), respectively. The mean incubation period of COVID-19 was 5.00 days (95% CI, 4.94-5.06 days) for cases caused by the Alpha variant, 4.50 days (95% CI, 1.83-7.17 days) for the Beta variant, 4.41 days (95% CI, 3.76-5.05 days) for the Delta variant, and 3.42 days (95% CI, 2.88-3.96 days) for the Omicron variant. The mean incubation was 7.43 days (95% CI, 5.75-9.11 days) among older patients (ie, aged over 60 years old), 8.82 days (95% CI, 8.19-9.45 days) among infected children (ages 18 years or younger), 6.99 days (95% CI, 6.07-7.92 days) among patients with nonsevere illness, and 6.69 days (95% CI, 4.53-8.85 days) among patients with severe illness. Conclusions and Relevance: The findings of this study suggest that SARS-CoV-2 has evolved and mutated continuously throughout the COVID-19 pandemic, producing variants with different enhanced transmission and virulence. Identifying the incubation period of different variants is a key factor in determining the isolation period.

Shorter Incubation Period among COVID-19 Cases with the BA.1 Omicron Variant.

We aimed to elucidate the range of the incubation period in patients infected with the SARS-CoV-2 Omicron variant in comparison with the Alpha variant. Contact tracing data from three Japanese public health centers (total residents, 1.06 million) collected following the guidelines of the Infectious Diseases Control Law were reviewed for 1589 PCR-confirmed COVID-19 cases diagnosed in January 2022. We identified 77 eligible symptomatic patients for whom the date and setting of transmission were known, in the absence of any other probable routes of transmission. The observed incubation period was 3.03 ± 1.35 days (mean ± SDM). In the log-normal distribution, 5th, 50th and 95th percentile values were 1.3 days (95% CI: 1.0-1.6), 2.8 days (2.5-3.1) and 5.8 days (4.8-7.5), significantly shorter than among the 51 patients with the Alpha variant diagnosed in April and May in 2021 (4.94 days ± 2.19, 2.1 days (1.5-2.7), 4.5 days (4.0-5.1) and 9.6 days (7.4-13.0), p < 0.001). As this incubation period, mainly of sublineage BA.1, is even shorter than that in the Delta variant, it is thought to partially explain the variant replacement occurring in late 2021 to early 2022 in many countries.

Incubation period, clinical and lung CT features for early prediction of COVID-19 deterioration: development and internal verification of a risk model.

BACKGROUND: Most severe, critical, or mortal COVID-19 cases often had a relatively stable period before their status worsened. We developed a deterioration risk model of COVID-19 (DRM-COVID-19) to predict exacerbation risk and optimize disease management on admission. METHOD: We conducted a multicenter retrospective cohort study with 239 confirmed symptomatic COVID-19 patients. A combination of the least absolute shrinkage and selection operator (LASSO), change-in-estimate (CIE) screened out independent risk factors for the multivariate logistic regression model (DRM-COVID-19) from 44 variables, including epidemiological, demographic, clinical, and lung CT features. The compound study endpoint was progression to severe, critical, or mortal status. Additionally, the model's performance was evaluated for discrimination, accuracy, calibration, and clinical utility, through internal validation using bootstrap resampling (1000 times). We used a nomogram and a network platform for model visualization. RESULTS: In the cohort study, 62 cases reached the compound endpoint, including 42 severe, 18 critical, and two mortal cases. DRM-COVID-19 included six factors: dyspnea [odds ratio (OR) 4.89;confidence interval (95% CI) 1.53-15.80], incubation period (OR 0.83; 95% CI 0.68-0.99), number of comorbidities (OR 1.76; 95% CI 1.03-3.05), D-dimer (OR 7.05; 95% CI, 1.35-45.7), C-reactive protein (OR 1.06; 95% CI 1.02-1.1), and semi-quantitative CT score (OR 1.50; 95% CI 1.27-1.82). The model showed good fitting (Hosmer-Lemeshow goodness, X2(8) = 7.0194, P = 0.53), high discrimination (the area under the receiver operating characteristic curve, AUROC, 0.971; 95% CI, 0.949-0.992), precision (Brier score = 0.051) as well as excellent calibration and clinical benefits. The precision-recall (PR) curve showed excellent classification performance of the model (AUCPR = 0.934). We prepared a nomogram and a freely available online prediction platform ( https://deterioration-risk-model-of-covid-19.shinyapps.io/DRMapp/ ). CONCLUSION: We developed a predictive model, which includes the including incubation period along with clinical and lung CT features. The model presented satisfactory prediction and discrimination performance for COVID-19 patients who might progress from mild or moderate to severe or critical on admission, improving the clinical prognosis and optimizing the medical resources.

Secondary Attack Rate, Transmission and Incubation Periods, and Serial Interval of SARS-CoV-2 Omicron Variant, Spain.

Contact tracing data of SARS-CoV-2 Omicron variant cases during December 2021 in Cantabria, Spain, showed increased transmission (secondary attack rate 39%) compared with Delta cases (secondary attack rate 26%), uninfluenced by vaccination status. Incubation and serial interval periods were also reduced. Half of Omicron transmissions happened before symptom onset in the index case-patient.

Shorter Incubation Period among Unvaccinated Delta Variant Coronavirus Disease 2019 Patients in Japan.

Few studies have assessed incubation periods of the severe acute respiratory syndrome coronavirus 2 Delta variant. This study aimed to elucidate the transmission dynamics, especially the incubation period, for the Delta variant compared with non-Delta strains. We studied unvaccinated coronavirus disease 2019 patients with definite single exposure date from August 2020 to September 2021 in Japan. The incubation periods were calculated and compared by Mann-Whitney U test for Delta (with L452R mutation) and non-Delta cases. We estimated mean and percentiles of incubation period by fitting parametric distribution to data in the Bayesian statistical framework. We enrolled 214 patients (121 Delta and 103 non-Delta cases) with one specific date of exposure to the virus. The mean incubation period was 3.7 days and 4.9 days for Delta and non-Delta cases, respectively (p-value = 0.000). When lognormal distributions were fitted, the estimated mean incubation periods were 3.7 (95% credible interval (CI) 3.4-4.0) and 5.0 (95% CI 4.5-5.6) days for Delta and non-Delta cases, respectively. The estimated 97.5th percentile of incubation period was 6.9 (95% CI 5.9-8.0) days and 10.4 (95% CI 8.6-12.7) days for Delta and non-Delta cases, respectively. Unvaccinated Delta variant cases had shorter incubation periods than non-Delta variant cases.

Joint Estimation of Generation Time and Incubation Period for Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a heavy disease burden globally. The impact of process and timing of data collection on the accuracy of estimation of key epidemiological distributions are unclear. Because infection times are typically unobserved, there are relatively few estimates of generation time distribution. METHODS: We developed a statistical framework to jointly estimate generation time and incubation period from human-to-human transmission pairs, accounting for sampling biases. We applied the framework on 80 laboratory-confirmed human-to-human transmission pairs in China. We further inferred the infectiousness profile, serial interval distribution, proportions of presymptomatic transmission, and basic reproduction number (R0) for COVID-19. RESULTS: The estimated mean incubation period was 4.8 days (95% confidence interval [CI], 4.1-5.6), and mean generation time was 5.7 days (95% CI, 4.8-6.5). The estimated R0 based on the estimated generation time was 2.2 (95% CI, 1.9-2.4). A simulation study suggested that our approach could provide unbiased estimates, insensitive to the width of exposure windows. CONCLUSIONS: Properly accounting for the timing and process of data collection is critical to have correct estimates of generation time and incubation period. R0 can be biased when it is derived based on serial interval as the proxy of generation time.

The Incubation Period Distribution of Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

Incubation period is an important parameter to inform quarantine period and to study transmission dynamics of infectious diseases. We conducted a systematic review and meta-analysis on published estimates of the incubation period distribution of coronavirus disease 2019, and showed that the pooled median of the point estimates of the mean, median and 95th percentile for incubation period are 6.3 days (range, 1.8-11.9 days), 5.4 days (range, 2.0-17.9 days), and 13.1 days (range, 3.2-17.8 days), respectively. Estimates of the mean and 95th percentile of the incubation period distribution were considerably shorter before the epidemic peak in China compared to after the peak, and variation was also noticed for different choices of methodological approach in estimation. Our findings implied that corrections may be needed before directly applying estimates of incubation period into control of or further studies on emerging infectious diseases.