Temporal Dynamics of Serum Perforin and Granzyme during the Acute Phase of SARS-CoV-2 Infection.

BACKGROUND: As many SARS-CoV-2 infections are asymptomatic, it could be useful to be able to determine how much time has passed since infection. We explored the changes in the temporal levels of T cell-related proteins (including perforin and granzymes) in the sera of patients with SARS-CoV-2 infection using a commercially available assay. METHODS: This study enrolled 36 patients infected with SARS-CoV-2 and 20 healthy control participants. Blood samples were collected at three different times based on the number of days since symptom onset (early phase: 1-5 days, mid-phase: 6-10 days, late phase: 11-18 days). We assessed the temporal changes in the serum levels of perforin and granzymes in patients with SARS-CoV-2 infection by comparing the results with those obtained in the healthy control group. RESULTS: We identified a significantly low level of perforin in the early phase of SARS-CoV-2 infection (p < 0.01), which was restored to normal during the mid- and late phases of the infection. However, there was no difference in the temporal change in the level of granzymes in SARS-CoV-2-infected patients compared to the healthy control group. CONCLUSIONS: This finding suggests that SARS-CoV-2 infection paralyzed the perforin expression in the early period immediately after infection. Thus, serum perforin is a potential marker for identifying the acute phase of SARS-CoV-2 infection.

Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample.

OBJECTIVES: We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea. METHODS: In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022. RESULTS: In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%. CONCLUSIONS: The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.

Temporal Dynamics of Serum Perforin and Granzymes in Three Different Clinical Stages of Virus-Induced Severe Fever with Thrombocytopenia Syndrome.

Virus-induced severe fever with thrombocytopenia syndrome (SFTS) induces a cell-mediated immune response that likely contributes to virus control in SFTS patients. To identify the temporal changes of the cell-mediated immune response, we investigated the changes in serum levels of perforin and granzymes at early periods after illness onset in SFTS patients. We analyzed 32 SFTS patients and compared the temporal patterns of serum perforin and granzyme A and B to that of 20 healthy control adults using the Mann-Whitney U test. Compared with healthy controls, the mean level of perforin was significantly reduced by 81% (P < 0.01) during the first week after illness onset, whereas granzyme B significantly increased by 4.6-fold (P = 0.02) in the first week after illness onset and decreased to normal afterward. During the study period, there was no significant difference in serum perforin and granzyme. These findings indicate that perforin and granzyme B in serum can be considered possible serologic markers that reflect the clinical stage of SFTS. Additional study is warranted for tracking circulating perforin and granzyme in different ages and for an extended period after illness onset.

The impact of the COVID-19 pandemic on chlamydia infection in South Korea: a comparison between the pre-pandemic and during-pandemic periods.

Background: Prior to COVID-19 pandemic, a yearly upward trajectory in the number of chlamydia infection cases was observed in South Korea. However, in response to the COVID-19 pandemic, Korea implemented several public health and social measures, which were shown to have an impact on the epidemiology of other infectious diseases. This study aimed to estimate the impact of the COVID-19 pandemic on the incidence and number of reported chlamydia infections in South Korea. Methods: Using the monthly number of reported chlamydia infection data between 2017 and 2022, we compared the trends in the reported numbers, and the incidence rates (IR) of chlamydia infection stratified by demographic characteristics (sex, age group, and region) in the pre- and during COVID-19 pandemic period (January 2017-December 2019 and January 2020-December 2022). Results: We observed an irregular downward trajectory in the number of chlamydia infection in the during-pandemic period. A 30% decrease in the total number of chlamydia infection was estimated in the during-pandemic compared to the pre-pandemic period, with the decrease greater among males (35%) than females (25%). In addition, there was a decrease in the cumulative incidence rate of the during COVID-19 pandemic period (IR: 0.43; 95% CI: 0.42-0.44) compared to the pre-pandemic period (IR: 0.60; 95% CI: 0.59-0.61). Conclusions: We identified decrease in the number of chlamydia infection during COVID-19 pandemic which is likely due to underdiagnosis and underreporting for the infection. Therefore, strengthening surveillance for sexually transmitted infections including chlamydia is warranted for an effective and timely response in case of an unexpected rebound in the number of the infections.

Association of public health and social measures on the hand-foot-mouth epidemic in South Korea.

BACKGROUND: School based-measures such as school closure and school holidays have been considered a viable intervention during the hand-foot-mouth disease (HFMD) epidemic. The aim of this study was to explore the association of nationwide public health and social measures (PHSMs) including planned school vacation on the transmissibility and attack rate of the HFMD epidemic in South Korea. METHODS: In this study, we used Korean national surveillance data on HFMD from 2014 to 2019 to estimate the temporal changes in HFMD transmissibility (instantaneous reproductive number, Rt). Furthermore, to assess the changes in the HFMD attack rate, we used a stochastic transmission model to simulate the HFMD epidemic with no school vacation and nationwide PHSMs in 2015 South Korea. RESULTS: We found that school vacations and 2015 PHSMs were associated with the reduced Rt by 2-7 % and 13 %, respectively. Model projections indicated school vacations and 2015 PHSMs were associated with reduced HFMD attack rate by an average of 1.10 % (range: 0.38-1.51 %). CONCLUSIONS: PHSMs likely have a larger association with reduced HFMD transmissibility than school-based measures alone (i.e. school vacations). Preventive measures targeting preschoolers could be considered as potential options for reducing the future burden of HFMD.

Correction: Relative bradycardia in patients with COVID-19.

[This corrects the article DOI: 10.1186/s42444-022-00073-z.].

Pediatric humoral immune responses and infection risk after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and two-dose vaccination during SARS-CoV-2 omicron BA.5 and BN.1 variants predominance in South Korea.

Background: Humoral immune responses and infection risk after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination during the Omicron BA.5 and BN.1 variants predominant period remains unexplored in pediatric population. Methods: We examined anti-spike (anti-S) immunoglobulin G (IgG) responses in a total of 986 children aged 4-18 years who visited outpatient clinics between June 2022 and January 2023, with a history of SARS-CoV-2 infection alone, completed two doses of COVID-19 vaccination alone, vaccine-breakthrough infection (i.e., infection after the single dose of vaccination), and no antigenic exposure. Furthermore, to determine SARS-CoV-2 infection risk, the incidence of newly developed SARS-CoV-2 infection was investigated up to March 2023. Results: The anti-S IgG levels in the 'vaccine-breakthrough infection' group exceeded those in the 'infection alone' and 'vaccination alone' groups (both P <0.01). Furthermore, the 'vaccination alone' group experienced more rapid anti-S IgG waning than the 'infection alone' and 'vaccine-breakthrough infection' groups (both P <0.01). We could not identify newly developed SARS-CoV-2 infection in the 'vaccine-breakthrough infection' group. Conclusion: Our findings suggest that hybrid immunity, acquired from SARS-CoV-2 infection and COVID-19 vaccination, was a potentially higher and longer-lasting humoral immune response and protected against SARS-CoV-2 infection in pediatric population during Omicron BA.5 and BN.1 variants predominant.

Epidemiology and Transmission Dynamics of Infectious Diseases and Control Measures.

The epidemiology and transmission dynamics of infectious diseases must be understood at the individual and community levels to improve public health decision-making for real-time and integrated community-based control strategies. Herein, we explore the epidemiological characteristics for assessing the impact of public health interventions in the community setting and their applications. Computational statistical methods could advance research on infectious disease epidemiology and accumulate scientific evidence of the potential impacts of pharmaceutical/nonpharmaceutical measures to mitigate or control infectious diseases in the community. Novel public health threats from emerging zoonotic infectious diseases are urgent issues. Given these direct and indirect mitigating impacts at various levels to different infectious diseases and their burdens, we must consider an integrated assessment approach, 'One Health', to understand the dynamics and control of infectious diseases.

Prediction of upcoming global infection burden of influenza seasons after relaxation of public health and social measures during the COVID-19 pandemic: a modelling study.

BACKGROUND: The transmission dynamics of influenza were affected by public health and social measures (PHSMs) implemented globally since early 2020 to mitigate the COVID-19 pandemic. We aimed to assess the effect of COVID-19 PHSMs on the transmissibility of influenza viruses and to predict upcoming influenza epidemics. METHODS: For this modelling study, we used surveillance data on influenza virus activity for 11 different locations and countries in 2017-22. We implemented a data-driven mechanistic predictive modelling framework to predict future influenza seasons on the basis of pre-COVID-19 dynamics and the effect of PHSMs during the COVID-19 pandemic. We simulated the potential excess burden of upcoming influenza epidemics in terms of fold rise in peak magnitude and epidemic size compared with pre-COVID-19 levels. We also examined how a proactive influenza vaccination programme could mitigate this effect. FINDINGS: We estimated that COVID-19 PHSMs reduced influenza transmissibility by a maximum of 17·3% (95% CI 13·3-21·4) to 40·6% (35·2-45·9) and attack rate by 5·1% (1·5-7·2) to 24·8% (20·8-27·5) in the 2019-20 influenza season. We estimated a 10-60% increase in the population susceptibility for influenza, which might lead to a maximum of 1-5-fold rise in peak magnitude and 1-4-fold rise in epidemic size for the upcoming 2022-23 influenza season across locations, with a significantly higher fold rise in Singapore and Taiwan. The infection burden could be mitigated by additional proactive one-off influenza vaccination programmes. INTERPRETATION: Our results suggest the potential for substantial increases in infection burden in upcoming influenza seasons across the globe. Strengthening influenza vaccination programmes is the best preventive measure to reduce the effect of influenza virus infections in the community. FUNDING: Health and Medical Research Fund, Hong Kong.

Incubation period of wild type of SARS-CoV-2 infections by age, gender, and epidemic periods.

Background: The incubation period of the coronavirus disease 2019 (COVID-19) is estimated to vary by demographic factors and the COVID-19 epidemic periods. Objective: This study examined the incubation period of the wild type of SARS-CoV-2 infections by the different age groups, gender, and epidemic periods in South Korea. Methods: We collected COVID-19 patient data from the Korean public health authorities and estimated the incubation period by fitting three different distributions, including log-normal, gamma, and Weibull distributions, after stratification by gender and age groups. To identify any temporal impact on the incubation period, we divided the study period into two different epidemic periods (Period-1: 19 January-19 April 2020 and Period-2: 20 April-16 October 2020), and assessed for any differences. Results: We identified the log-normal as the best-fit model. The estimated median incubation period was 4.6 (95% CI: 3.9-4.9) days, and the 95th percentile was 11.7 (95% CI: 10.2-12.2) days. We found that the incubation period did not differ significantly between males and females (p = 0.42), age groups (p = 0.60), and the two different epidemic periods (p = 0.77). Conclusions: The incubation period of wild type of SARS-CoV-2 infection during the COVID-19 pandemic 2020, in South Korea, does not likely differ by age group, gender and epidemic period.

Estimating the incubation period of SARS-CoV-2 Omicron BA.1 variant in comparison with that during the Delta variant dominance in South Korea.

Based on exposure history and symptom onset of 22 Omicron BA.1 cases in South Korea from November to December 2021, we estimated mean incubation period of 3.5 days (95% CI: 2.5, 3.8), and then compared to that of 6.5 days (95% CI: 5.3, 7.7) for 64 cases during Delta variants' dominance in June 2021. For Omicron BA.1 variants, we found that 95% of symptomatic cases developed clinical conditions within 6.0 days (95% CI: 4.3, 6.6) after exposure. Thus, a shorter quarantine period may be considered based on symptoms, or similarly laboratory testing, when Omicron BA.1 variants are circulating.

Decreased door-to-balloon time in patients with ST-segment elevation myocardial infarction during the early COVID-19 pandemic in South Korea: An observational study.

The coronavirus disease 2019 (COVID-19) resulted in a marked decrease in the number of patient visits for acute myocardial infarction and delayed patient response and intervention in several countries. This study evaluated the effect of the COVID-19 pandemic on the number of patients, patient response time (pain-to-door), and intervention time (door-to-balloon) for patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). Patients with STEMI or NSTEMI visiting a hospital in South Korea who underwent primary coronary intervention during the COVID-19 pandemic (January 29, 2020, to December 31, 2020) were compared with those in the equivalent period from 2018 to 2019. Patient response and intervention times were compared for the COVID-19 pandemic window (2020) and the equivalent period from 2018 to 2019. We observed no decrease in the number of patients with STEMI (P = .88) and NSTEMI (P = 1.00) during the COVID-19 pandemic compared to that in the previous years. Patient response times (STEMI: P = .39; NSTEMI: P = .59) during the overall COVID-19 pandemic period did not differ significantly. However, we identified a significant decrease in door-to-balloon time among patients with STEMI (14%; P < .01) during the early COVID-19 pandemic. We found that the number of patients with STEMI and NSTEMI was consistent during the COVID-19 pandemic and that no time delays in patient response and intervention occurred. However, the door-to-balloon time among patients with STEMI significantly reduced during the early COVID-19 pandemic, which could be attributed to decreased emergency care utilization during the early pandemic.

Characterizing superspreading potential of infectious disease: Decomposition of individual transmissibility.

In the context of infectious disease transmission, high heterogeneity in individual infectiousness indicates that a few index cases can generate large numbers of secondary cases, a phenomenon commonly known as superspreading. The potential of disease superspreading can be characterized by describing the distribution of secondary cases (of each seed case) as a negative binomial (NB) distribution with the dispersion parameter, k. Based on the feature of NB distribution, there must be a proportion of individuals with individual reproduction number of almost 0, which appears restricted and unrealistic. To overcome this limitation, we generalized the compound structure of a Poisson rate and included an additional parameter, and divided the reproduction number into independent and additive fixed and variable components. Then, the secondary cases followed a Delaporte distribution. We demonstrated that the Delaporte distribution was important for understanding the characteristics of disease transmission, which generated new insights distinct from the NB model. By using real-world dataset, the Delaporte distribution provides improvements in describing the distributions of COVID-19 and SARS cases compared to the NB distribution. The model selection yielded increasing statistical power with larger sample sizes as well as conservative type I error in detecting the improvement in fitting with the likelihood ratio (LR) test. Numerical simulation revealed that the control strategy-making process may benefit from monitoring the transmission characteristics under the Delaporte framework. Our findings highlighted that for the COVID-19 pandemic, population-wide interventions may control disease transmission on a general scale before recommending the high-risk-specific control strategies.