Risk factors for deaths associated with COVID-19 according to the cause of death classification in Republic of Korea.

OBJECTIVES: This study aimed to classify coronavirus disease 2019 (COVID-19)-related deaths according to whether COVID-19 was listed as the cause of death, and to investigate the differences in demographic characteristics and risk factors for COVID-19 death classifications. METHODS: A total of 5,625 deaths in South Korea among patients with confirmed COVID-19 from January 20, 2020 to December 31, 2021 were selected. Excluding false reports and unnatural deaths, 5,597 deaths were analyzed. Based on death report data, deaths were classified according to whether the cause of death was listed as COVID-19 (CD) or not (NCD). The epidemiological characteristics and causes of deaths were investigated using descriptive, univariate, and multivariate statistical analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to analyze the risk factors. RESULTS: The case fatality ratio was 0.89% and increased with age. Additionally, 96.4% of the subjects had an underlying disease, and 53.4% died in winter. The proportion of NCDs was 9.3%, of whom 19.1% died at home and 39.0% were confirmed to have COVID-19 after death. Malignant neoplasms (102/416 vs. 637/4,442; OR, 1.71; 95% CI, 1.36-2.16; p<0.001) were significantly associated with NCD. CONCLUSION: This is the first study to analyze risk factors by cause of death using COVID-19 death report data in South Korea. These results are expected to be used as evidence for establishing a death monitoring system that can collect timely information in a new infectious disease pandemic.

Effect of socioeconomic disparities on the risk of COVID-19 in eight metropolitan cities, the Republic of Korea: a community-based study.

Objectives: Socioeconomic disparities have been reported as the main risk factors contributing to the spread of coronavirus disease 2019 (COVID-19) at the community level. We conducted an epidemiological study on the risk of COVID-19 incidence using area deprivation indices (DIs) depending on the characteristics of the susceptible population. Methods: The database of the confirmed COVID-19 cases in eight metropolitan cities, the Republic of Korea, from January 20, 2020 to December 31, 2021, was combined with the area DIs and standardized prevalence of diabetes and hypertension from the community health survey. The relative risk (RR) was estimated using a generalized linear model with Poisson distribution by age group. Results: The risk of COVID-19 incidence increased with the increasing age group, especially in patients aged ≥75 years. The RR per interquartile range increment of total social deprivation index (total SDI) was 1.54 (95% confidence interval [CI]: 1.34-1.70) in the COVID-19 incidence. Especially, the risk of COVID-19 incidence in the first wave was about three times higher in the region belonging to the lowest socioeconomic status than in the region with the highest socioeconomic status. The risk was 3.08 (95% CI: 2.42 to 3.78) based on the total SDI and 3.13 (95% CI: 2.53 to 3.83) based on the social deprivation index. Conclusion: This study provides scientific evidence that socioeconomic inequity is an important risk factor for the spread of COVID-19. This finding suggests that a mid-to-long-term strategy is needed for the susceptible population to reduce the burden of COVID-19 in the community.

Deciphering changes in the incidence of the Guillain-Barré syndrome during the COVID-19 pandemic: a nationwide time-series correlation study.

Background: Postinfectious autoimmunity is a hallmark of Guillain-Barré syndrome (GBS), and GBS incidence closely parallels that of its immune triggers. Sociobehavioural interventions implemented during the COVID-19 pandemic have altered the infectious disease landscape. Methods: This nationwide time-series correlation study analysed GBS incidence, sentinel surveillance and SARS-CoV-2 vaccination data from January 2017 to December 2021 in the National Health Insurance Service and Korean Disease Control and Prevention Agency databases. The incidence of GBS and sentinel gastrointestinal and respiratory infectious diseases during the pandemic (2020-2021) was estimated and compared with both prepandemic (2017-2019) and incidence predicted in a time-series forecasting model. Time-series correlation analysis was used to examine the temporal association between GBS, infectious triggers and SARS-CoV-2 vaccination. Results: During the pandemic, the total crude cumulative incidence rate was 2.1 per 100 000 population, which is lower than the prepandemic incidence, especially in age groups of less than 60 years. Seasonality was briefly interrupted during the winter of 2021. The majority of respiratory and some gastrointestinal conditions had a lower-than-expected incidence during the pandemic. Compared with the prepandemic state, during the pandemic period a higher number of gastrointestinal pathogens (Escherichia coli, Campylobacter spp., Clostridium perfringens, Yersinia enterocolitica and enteric adenovirus) had significant, moderate-to-strong positive temporal associations with GBS. The temporal association between SARS-CoV-2 infection and GBS was not significant, but SARS-CoV-2 vaccination exhibited a strong positive temporal association with GBS in 2021. Conclusion: The incidence of GBS and sentinel infectious diseases decreased to below-expected levels during the pandemic, with the former attributable to the decreased incidence of non-COVID-19 respiratory and gastrointestinal infections. The evolving incidence of autoimmune postinfectious phenomena following the pandemic needs attention.

Pediatric Deaths Associated With Coronavirus Disease 2019 (COVID-19) in Korea.

As of September 3, 2022, 5,388,338 coronavirus disease 2019 (COVID-19) cases and 46 deaths (3 in 2021 and 43 in 2022) were reported in children ≤ 18 years in Korea. Cumulative confirmed cases accounted for 67.3% of the population aged ≤ 18 years and case fatality rate was 0.85/100,000. Among 46 fatal cases, 58.7% were male and median age was 7 years. Underlying diseases were present in 47.8%; neurologic diseases (63.6%) and malignancy (13.6%) most common. Only four had history of COVID-19 immunization. COVID-19 associated deaths occurred at median 2 days from diagnosis (range: -1 to 21). Among COVID-19 deaths, 41.3% occurred before admission; 2 before hospital arrival and 17 in the emergency department. Among children whose cause was documented, myocarditis, respiratory and multiorgan failure were most common. COVID-19 associated death was seen early after diagnosis in children and public health policies to provide access to medical care for children with COVID-19 are essential during the pandemic.

Transmission Potential of the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 in South Korea, 25 November 2021-8 January 2022.

Our study indicates sustained transmission (effective reproduction number, 1.3; serial interval, 4.2 days; regional doubling times, 3.3-11.4 days) of the severe acute respiratory syndrome coronavirus 2 Omicron (B.1.1.529) variant (N = 2351) in South Korea (25 November 2021-8 January 2022), implicating insufficient protection through vaccination and supporting nonpharmaceutical control measures.

Seroprevalence of SARS-CoV-2 antibodies in the community based on participants in the 2020 Korea National Health and Nutrition Examination Survey.

OBJECTIVES: The Korea National Health and Nutrition Examination Survey (KNHANES) is a nationwide cross-sectional surveillance system that assesses the health and nutritional status of the Korean population. To evaluate the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the community, we investigated the prevalence of anti-SARS-CoV-2 antibodies in the sera of KNHANES participants. METHODS: Subjects were recruited between April 24 and December 12, 2020. In total, 5,284 subjects aged 10-90 years from 17 regions participated. SARS-CoV-2 antibodies were screened using the Elecsys Anti-SARS-CoV-2 assay. Positive samples were verified using 4 different SARS-CoV-2 antibody assays and the plaque reduction neutralizing test. The final seropositivity criteria were a positive screening test and at least 1 positive result from the 5 additional tests. RESULTS: Almost half (49.2%; 2,600/5,284) of participants were from metropolitan areas, 48.9% were middle-aged (40-69 years), and 20.5% were in their 20s or younger. The seropositivity rate was 0.09% (5/5,284). Three of the 5 antibody-positive subjects had a history of infection, of whom 2 were infected abroad and 1 was infected in a local cluster outbreak. CONCLUSIONS: The low SARS-CoV-2 antibody seroprevalence in Korea indicates that there have been few coronavirus disease 2019 (COVID-19) cases due to successful COVID-19 management measures (e.g., diagnostic tests for overseas arrivals, national social distancing, and strict quarantine measures). Moreover, asymptomatic infections were uncommon due to active polymerase chain reaction testing. However, hidden infections may exist in the community, requiring the continuation of quarantine and vaccination measures.

Multi-Faceted Analysis of COVID-19 Epidemic in Korea Considering Omicron Variant: Mathematical Modeling-Based Study.

BACKGROUND: The most recent variant of concern, omicron (B.1.1.529), has caused numerous cases worldwide including the Republic of Korea due to its fast transmission and reduced vaccine effectiveness. METHODS: A mathematical model considering age-structure, vaccine, antiviral drugs, and influx of the omicron variant was developed. We estimated transmission rates among age groups using maximum likelihood estimation for the age-structured model. The impact of non-pharmaceutical interventions (NPIs; in community and border), quantified by a parameter µ in the force of infection, and vaccination were examined through a multi-faceted analysis. A theory-based endemic equilibrium study was performed to find the manageable number of cases according to omicron- and healthcare-related factors. RESULTS: By fitting the model to the available data, the estimated values of µ ranged from 0.31 to 0.73, representing the intensity of NPIs such as social distancing level. If µ < 0.55 and 300,000 booster shots were administered daily from February 3, 2022, the number of severe cases was forecasted to exceed the severe bed capacity. Moreover, the number of daily cases is reduced as the timing of screening measures is delayed. If screening measure was intensified as early as November 24, 2021 and the number of overseas entrant cases was contained to 1 case per 10 days, simulations showed that the daily incidence by February 3, 2022 could have been reduced by 87%. Furthermore, we found that the incidence number in mid-December 2021 exceeded the theory-driven manageable number of daily cases. CONCLUSION: NPIs, vaccination, and antiviral drugs influence the spread of omicron and number of severe cases in the Republic of Korea. Intensive and early screening measures during the emergence of a new variant is key in controlling the epidemic size. Using the endemic equilibrium of the model, a formula for the manageable daily cases depending on the severity rate and average length of hospital stay was derived so that the number of severe cases does not surpass the severe bed capacity.

An analysis of the dynamic spatial spread of COVID-19 across South Korea.

The first case of coronavirus disease 2019 (COVID-19) in South Korea was confirmed on January 20, 2020, approximately three weeks after the report of the first COVID-19 case in Wuhan, China. By September 15, 2021, the number of cases in South Korea had increased to 277,989. Thus, it is important to better understand geographical transmission and design effective local-level pandemic plans across the country over the long term. We conducted a spatiotemporal analysis of weekly COVID-19 cases in South Korea from February 1, 2020, to May 30, 2021, in each administrative region. For the spatial domain, we first covered the entire country and then focused on metropolitan areas, including Seoul, Gyeonggi-do, and Incheon. Moran's I and spatial scan statistics were used for spatial analysis. The temporal variation and dynamics of COVID-19 cases were investigated with various statistical visualization methods. We found time-varying clusters of COVID-19 in South Korea using a range of statistical methods. In the early stage, the spatial hotspots were focused in Daegu and Gyeongsangbuk-do. Then, metropolitan areas were detected as hotspots in December 2020. In our study, we conducted a time-varying spatial analysis of COVID-19 across the entirety of South Korea over a long-term period and found a powerful approach to demonstrating the current dynamics of spatial clustering and understanding the dynamic effects of policies on COVID-19 across South Korea. Additionally, the proposed spatiotemporal methods are very useful for understanding the spatial dynamics of COVID-19 in South Korea.

Transmission potential of the Omicron variant of SARS-CoV-2 in South Korea: From November 25, 2020 to January 8, 2022

Our study indicates sustained transmission (effective reproduction number 1.3;serial interval 4.2 days;regional doubling times 3.3–11.4 days) of the severe acute respiratory syndrome coronavirus 2 Omicron (B.1.1.529) variant (n = 2351) in South Korea (November 25, 2021–January 8, 2022), implicating insufficient protection through vaccination and supporting non-pharmaceutical control measures.

Comparison of the Prevalence of Antibodies to SARS-CoV-2 in 9954 Recruits in the Korean Army Training Center with the General Korean Population of Equivalent Age Between September and November, 2020.

BACKGROUND Understanding the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be a useful tool when studying spread of the disease. This study aimed to compare the prevalence of antibodies to SARS-CoV-2 in 9954 recruits in the Korean Army Training Center with the general Korean population age <30 years between September and November, 2020. MATERIAL AND METHODS At the Korean Army Training Center, samples were taken from 9954 men from September to November, 2020. Participants were randomly enlisted healthy adult men. The data were compared with 4,205,265 samples from the Korean general population. Men age <30 years were used, as this is similar to the age range of the military recruits. RESULTS Among military recruits, 31 subjects (0.31%) were positive for the antibody, while the Korean male population had 3757 (0.09%) positive individuals. Among these 31 men, 13 were previously diagnosed by PCR, while 18 (58.06%) had no history related to the disease. Positive military recruits were mostly from 2 regional clusters. The first cluster was Daegu and Gyeongbuk areas (1.97% and 0.80%, respectively), which had an outbreak in March, 2020. The second cluster was Gyeonggi and Seoul, or capital areas (0.23% and 0.20%, respectively), which currently has high PCR positivity. Overall, seroprevalence was 3.49 times higher in study subjects. CONCLUSIONS The high seroprevalence of antibodies to SARS-CoV-2 between September and November 2020 in a densely populated military academy in Korea may have been an indicator for the resulting outbreak of COVID-19 in winter 2020-21, which highlights the importance of asymptomatic spread from the young and healthy to the general population.

Increase in Viral Load in Patients With SARS-CoV-2 Delta Variant Infection in the Republic of Korea.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly, causing in COVID-19 being declared a global pandemic by the World Health Organization. The key variants include alpha, beta, gamma, and delta; these exhibit high viral transmission, pathogenicity, and immune evasion mechanisms. The delta variant, first confirmed in India, was detected in the majority of COVID-19 patients at the recent wave in the Republic of Korea. Here, the features of the delta variant were compared to the earlier waves, with focus on increased transmissibility. The viral load, from the initial days of infection to 14 days later, was compared based on epidemiological data collected at the time of confirmed diagnosis. The increased viral load observed in the delta variant-led infections influences the scale of the wave, owing to the increased rate of transmission. Infections caused by the delta variant increases the risk of hospitalization within 14 days after symptom onset, and the high viral load correlates with COVID-19 associated morbidity and mortality. Therefore, the future studies should compare the trend of disease severity caused by the high viral load of delta variant with previous waves and analyze the vaccine effects in light of the delta variant of fourth wave.

Epidemiological Characteristics and Transmission Patterns of COVID-19 Cases Among Children and Adolescents Aged 0-18 Years in South Korea.

BACKGROUND: In South Korea, the epidemiological characteristics of children and adolescents infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have not been reported to date. The purpose of this study was to identify major epidemiological characteristics and transmission patterns of coronavirus disease 2019 (COVID-19) in children and adolescents. METHODS: This study was conducted through a system integrated in an epidemiological investigation by the Korea Disease Control and Prevention Agency from January 20, 2020, to June 5, 2021. We analyzed the epidemiological characteristics of 14,967 children and adolescents with COVID-19 according to the age groups and transmission age patterns of 3721 infector-infectee pairs in South Korea. RESULTS: Among the total confirmed COVID-19 cases, 14,967 patients were aged 0-18 years. The most affected age group among children and adolescents were those aged 16-18 years (3589, 24.0%). For all age groups, the infection route through friends and family members (31.9%) was the highest. For the contact age pattern analysis, infection from infectors aged 30-49 years to infectees aged 0-12 years showed a statistically significant relation (p <0.001) compared to that in other age groups. On the other hand, among the infectees aged 13-15 years and 16-18 years were significantly related with adolescents aged 10-19 years (p <0.05). CONCLUSION: These results suggest that adolescents aged 13-18 years were more infected with COVID-19 than those aged 0-12 years. Furthermore, they are particularly more likely to be infected by friends and family members. Besides, in patients aged 13-18 years, transmission of SARS-CoV-2 was more common from adolescents to adolescents than from adults to adolescents. This research will provide scientific evidence for school policies and vaccine strategies for COVID-19 prevention in children and adolescents.

Review of the early reports of the epidemiological characteristics of the B.1.1.7 variant of SARS-CoV-2 and its spread worldwide.

The variant B.1.1.7 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the RNA virus causing the pandemic more than a year worldwide, was reported from United Kingdom (UK) in late December 2020. It was reported that mortality increases by 65% and transmissibility increases by 70%, which may result in an increase of reproduction number to 1.13-1.55 from 0.75-0.85. To analyze the global increasing trend of the variant B.1.1.7, we extracted results of B.1.1.7 from GISAID on May 11 and May 12, 2021, and conducted a doseresponse regression. It took 47 days to reach 20% and 121 days to reach 50% among the sequence submitted from UK. In Korea, cases of B.1.1.7 have increased since the first report of three cases on December 28, 2020. Positive rate of B.1.1.7 in Korea was 21.6% in the week from May 9 to May 15, 2021. Detection rate of the variants is expected to increase further and new variants of SARS-CoV-2 are emerging, so a close monitoring and control would be maintained for months.

COVID-19 Vaccine Priority Strategy Using a Heterogenous Transmission Model Based on Maximum Likelihood Estimation in the Republic of Korea.

(1) Background: The vaccine supply is likely to be limited in 2021 due to constraints in manufacturing. To maximize the benefit from the rollout phase, an optimal strategy of vaccine allocation is necessary based on each country's epidemic status. (2) Methods: We first developed a heterogeneous population model considering the transmission matrix using maximum likelihood estimation based on the epidemiological records of individual COVID-19 cases in the Republic of Korea. Using this model, the vaccine priorities for minimizing mortality or incidence were investigated. (3) Results: The simulation results showed that the optimal vaccine allocation strategy to minimize the mortality (or incidence) was to prioritize elderly and healthcare workers (or adults) as long as the reproductive number was below 1.2 (or over 0.9). (4) Conclusion: Our simulation results support the current Korean government vaccination priority strategy, which prioritizes healthcare workers and senior groups to minimize mortality, under the condition that the reproductive number remains below 1.2. This study revealed that, in order to maintain the current vaccine priority policy, it is important to ensure that the reproductive number does not exceed the threshold by concurrently implementing nonpharmaceutical interventions.

Genomic Surveillance of SARS-CoV-2: Distribution of Clades in the Republic of Korea in 2020.

Since a novel beta-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019, there has been a rapid global spread of the virus. Genomic surveillance was conducted on samples isolated from infected individuals to monitor the spread of genetic variants of SARS-CoV-2 in Korea. The Korea Disease Control and Prevention Agency performed whole genome sequencing of SARS-CoV-2 in Korea for 1 year (January 2020 to January 2021). A total of 2,488 SARS-CoV-2 cases were sequenced (including 648 cases from abroad). Initially, the prevalent clades of SARS-CoV-2 were the S and V clades, however, by March 2020, GH clade was the most dominant. Only international travelers were identified as having G or GR clades, and since the first variant 501Y.V1 was identified (from a traveler from the United Kingdom on December 22nd, 2020), a total of 27 variants of 501Y.V1, 501Y.V2, and 484K.V2 have been classified (as of January 25th, 2021). The results in this study indicated that quarantining of travelers entering Korea successfully prevented dissemination of the SARS-CoV-2 variants in Korea.