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As coronavirus disease-2019 (COVID-19) becomes an endemic disease, the virus continues to evolve and become immunologically distinct from previous strains. Immune imprinting has raised concerns about bivalent mRNA vaccines containing both ancestral virus and Omicron variant. To increase efficacy against the predominant strains as of the second half of 2023, the updated vaccine formulation contained only the mRNA of XBB.1.5 sublineage. We conducted a multicenter, test-negative, case-control study to estimate XBB.1.5 monovalent vaccine effectiveness (VE) and present the results of an interim analysis with data collected in November 2023. Patients who underwent COVID-19 testing at eight university hospitals were included and matched based on age (19-49, 50-64, and ≥65 years) and sex in a 1:1 ratio. VE was calculated using the adjusted odds ratio derived from multivariable logistic regression. Of the 992 patients included, 49 (5.3%) received the XBB.1.5 monovalent vaccine at least 7 days before COVID-19 testing. Patients with COVID-19 (cases) were less likely to have received the XBB.1.5 monovalent vaccine (case 3.5% vs. control 7.2%, p=0.019) and to have a history of COVID-19 within 6 months (2.2% vs. 4.6%, p=0.068). In contrast, patients with COVID-19 were more likely to be healthcare workers (8.2% vs. 3.0%, p=0.001) and to have chronic neurological diseases (16.7% vs. 11.9%, p=0.048). The adjusted VE of the XBB.1.5 monovalent mRNA vaccine was 56.8% (95% confidence interval: 18.7-77.9%). XBB.1.5 monovalent mRNA vaccine provided significant protection against COVID-19 in the first one to two months after vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nham, Sohn, Choi, Wie, Lee, Lee, Jeong, Eom, Choi, Seong, Yoon, Noh, Song, Cheong and Kim.)

Background: The assessment of long-term humoral and cellular immunity post-vaccination is crucial for establishing an optimal vaccination strategy., Methods: This prospective cohort study evaluated adults (≥18 years) who received a BA.4/5 bivalent vaccine. We measured the anti-receptor binding domain immunoglobulin G antibody and neutralizing antibodies (NAb) against wild-type and Omicron subvariants (BA.5, BQ.1.1, BN.1, XBB.1 and EG.5) up to 9 months post-vaccination. T-cell immune responses were measured before and 4 weeks after vaccination., Results: A total of 108 (28 SARS-CoV-2-naïve and 80 previously infected) participants were enrolled. Anti-receptor binding domain immunoglobulin G (U/mL) levels were higher at 9 months post-vaccination than baseline in SAR-CoV-2-naïve individuals (8,339 vs. 1,834, p<0.001). NAb titers against BQ.1.1, BN.1, and XBB.1 were significantly higher at 9 months post-vaccination than baseline in both groups, whereas NAb against EG.5 was negligible at all time points. The T-cell immune response (median spot forming unit/10 6 cells) was highly cross-reactive at both baseline (wild-type/BA.5/XBB.1.5, 38.3/52.5/45.0 in SARS-CoV-2-naïve individuals; 51.6/54.9/54.9 in SARS-CoV-2-infected individuals) and 4 weeks post-vaccination, with insignificant boosting post-vaccination., Conclusion: Remarkable cross-reactive neutralization was observed against BQ.1.1, BN.1, and XBB.1 up to 9 months after BA.4/5 bivalent vaccination, but not against EG.5. The T-cell immune response was highly cross-reactive., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hyun, Nham, Seong, Yoon, Noh, Cheong, Kim, Yoon, Park, Gwak, Lee, Kim and Song.)

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergency of various lineages through mutations and recombination. In the Delta lineage, we identified recombination events in the ORF1a gene, which divided the Delta sublineages into three different genotypes (Delta R1-R3). The regional distributions of Delta R1 and Delta R2 were not correlated, indicating that recombination occurred early in the Delta outbreak. The impact of the ORF1a gene on SARS-CoV-2 transmission remains unclear; however, our findings suggest that recombination may have contributed to the evolution and global spread of the Delta lineage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Bivalent booster mRNA vaccines containing the omicron-variant strains have been introduced worldwide in the autumn of 2022. Nevertheless, the omicron subvariants evoked another large coronavirus disease 2019 (COVID-19) pandemic wave in late 2022 and early 2023., Methods: A retrospective, test-negative, case-control study was conducted to estimate the vaccine effectiveness (VE) of bivalent COVID-19 vaccines in 8 university hospitals between January and February 2023. The case and control groups were divided based on nasopharyngeal COVID-19 real-time polymerase chain reaction results and matched based on age, sex, hospital, and date (week) of the test performed. The VE of the BA.1- or BA.4/BA.5-based mRNA vaccines were estimated. VE was calculated using the 1-adjusted odds ratio from multivariable logistic regression., Results: In total, 949 patients and 947 controls were enrolled in this study. VE for the BA.4/BA.5-based bivalent mRNA vaccine was 43% (95% confidence interval [CI], 17, 61%). In subgroup analysis based on age and underlying medical conditions, BA.4/BA.5-based bivalent mRNA vaccine was effective against old adults aged ≥ 65-years (VE, 55%; 95% CI, 23, 73%) and individuals with comorbidities (VE, 54%; 95% CI, 23, 73%). In comparison, the BA.1-based bivalent mRNA vaccine did not demonstrate statistically significant effectiveness (VE, 25%; 95% CI, -8, 49%)., Conclusion: The BA.4/BA.5-based bivalent mRNA booster vaccine provided significant protection against COVID-19 in the Korean adults, especially in the older adults aged ≥ 65 years and in individuals with underlying medical conditions., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Following the global emergence of the SARS-CoV-2 Alpha variant of concern (VOC) in 2020, the Delta variant triggered another wave in 2021. The AY.69 lineage, a Delta VOC, was particularly prevalent in Republic of Korea (South Korea) from May 2021 to January 2022, despite the synchronized implementation of vaccination programmes and non-pharmaceutical interventions (NPIs) such as social distancing. In this study, we used phylogeographic analysis combined with a generalized linear model (GLM) to examine the impact of human movement and vaccination on viral transmission. Our findings indicated that transmission primarily originated in South Korea's metropolitan areas, and a positive correlation was observed between total human mobility (tracked by GPS on mobile phones and estimated through credit card consumption) and viral spread. The phylodynamic analysis further revealed that non-vaccinated individuals were the primary transmitters of the virus during the study period, even though vaccination programmes had commenced three months prior to the AY.69 outbreak. Our study emphasizes the need to focus on controlling SARS-CoV-2 transmission in metropolitan regions and among unvaccinated populations. Furthermore, the positive correlation between mobility data and viral dissemination could contribute to the development of more accurate predictive models for local spread of pandemics.

Background: Our study aimed to determine the risk of herpes zoster reactivation and coronavirus disease 2019 (COVID-19) vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19])., Methods: This retrospective study analyzed herpes zoster cases diagnosed between 26 February 2021 and 30 June 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed., Results: In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose adjusted odds ratio [aOR], 1.11; 95% confidence interval [CI], 1.06-1.15; second dose aOR, 1.17; 95% CI, 1.12-1.23). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR], 1.09; 95% CI, 1.02-1.16). BNT162b2 was associated with an increased risk at 18 days postvaccination (aHR, 1.65; 95% CI, 1.35-2.02) and second dose (aHR, 1.10; 95% CI, 1.02-1.19). However, the risk did not increase in both analyses of ChAdOx1 vaccination., Conclusions: mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: The study determined the effects of online continuing medical education (CME) on the clinical competency, performance, and patient outcomes of physicians and other healthcare professionals during the COVID-19 pandemic regarding the topics of COVID-19 and back pain., Methods: Survey studies on six online CME activities were conducted from April 2020 to February 2021 at a South Korean hospital. Surveys were conducted immediately after and three months after the CME activity to measure the effectiveness of the CME activity regarding professional competence and performance, as well as patient outcomes., Results: A total of 624 individuals participated in the six CME activities. Of the 2007 post-activity responses, a total of 1135 out of 1332 (85.21%) participants indicated that they were satisfied with the online education activities, and a total of 1752 out of 2007 (87.29%) participants responded that the content would influence their clinical practice. Upon a three-month follow-up, 477 out of 611 (78.07%) respondents indicated that they had made actual changes to their clinical practice., Conclusions: The online delivery method is effective for delivering CME. The results suggest that online CME ultimately influences physicians' clinical competency and performance, which leads to enforcing change in clinical practice.

Coronavirus disease 2019 (Covid-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) became a pandemic, causing significant burden on public health worldwide. Although the timely development and production of mRNA and adenoviral vector vaccines against SARS-CoV-2 have been successful, issues still exist in vaccine platforms for wide use and production. With the potential for proliferative capability and heat stability, the Newcastle disease virus (NDV)-vectored vaccine is a highly economical and conceivable candidate for treating emerging diseases. In this study, a recombinant NDV-vectored vaccine expressing the spike (S) protein of SARS-CoV-2, rK148/beta-S, was developed and evaluated for its efficacy against SARS-CoV-2 in K18-hACE-2 transgenic mice. Intramuscular vaccination with low dose (10 6.0 EID 50 ) conferred a survival rate of 76 % after lethal challenge of a SARS-CoV-2 beta (B.1.351) variant. When administered with a high dose (10 7.0 EID 50 ), vaccinated mice exhibited 100 % survival rate and reduced lung viral load against both beta and delta variants (B.1.617.2). Together with the protective immunity, rK148/beta-S is an accessible and cost-effective SARS-CoV-2 vaccine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Rationale: Light-chain deposition disease (LCDD) is a rare condition characterized by the abnormal deposition of monoclonal light chains (LCs) in multiple organs, leading to progressive organ dysfunction. Herein, we report a case of plasma cell myeloma initially diagnosed as LCDD on liver biopsy performed for prominent cholestatic hepatitis., Patient Concerns: A 55-year-old Korean man complained of dyspepsia as the main symptom. On abdominal computed tomography performed at another hospital, the liver showed mildly decreased and heterogeneous attenuation with mild periportal edema. Preliminary liver function tests revealed abnormal results. The patient was treated for an unspecified liver disease; however, his jaundice gradually worsened, prompting him to visit our outpatient hepatology clinic for further evaluation. Magnetic resonance cholangiography revealed liver cirrhosis with severe hepatomegaly of unknown cause. A liver biopsy was performed for the diagnosis. Hematoxylin and eosin staining revealed diffuse extracellular amorphous deposits in perisinusoidal spaces with compressed hepatocytes. The deposits, which morphologically resembled amyloids, were not stained by Congo red but stained strongly positive for kappa LCs and weakly positive for lambda LCs., Diagnoses: Therefore, the patient was diagnosed with LCDD. Further systemic examination revealed a plasma cell myeloma., Interventions: Fluorescence in situ hybridization, cytogenetics, and next-generation sequencing tested in bone marrow showed no abnormalities. The patient initially received bortezomib/lenalidomide/dexamethasone as the treatment regimen for plasma cell myeloma., Outcomes: However, he died shortly thereafter because of coronavirus disease 2019 complications., Lessons: This case demonstrates that LCDD may present with sudden cholestatic hepatitis and hepatomegaly, and may be fatal if patients do not receive appropriate and timely treatment because of delayed diagnosis. Liver biopsy is useful for the diagnosis of patients with liver disease of unknown etiology., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gut luminal cells through the angiotensin-converting enzyme-2 receptor and disrupts the gut microbiome. We investigated whether the gut microbiome in the early stage of SARS-CoV-2 infection was associated with the prognosis of coronavirus disease (COVID-19)., Methods: Thirty COVID-19 patients and 16 healthy controls were prospectively enrolled. Blood and stool samples and clinical details were collected on days 0 (enrollment), 7, 14, and 28. Participants were categorized into four groups by their clinical course., Results: Gut microbiota composition varied during the clinical course of COVID-19 and was closely associated with cytokine levels ( p =0.003). A high abundance of the genus Dialister (linear discriminant analysis [LDA] effect size: 3.97856, p =0.004), species Peptoniphilus lacrimalis (LDA effect size: 4.00551, p =0.020), and Anaerococcus prevotii (LDA effect size: 4.00885, p =0.007) was associated with a good prognosis. Starch, sucrose, and galactose metabolism was highly activated in the gut microbiota of the poor prognosis group. Glucose-lowering diets, including whole grains, were positively correlated with a good prognosis., Conclusion: Gut microbiota may mediate the prognosis of COVID-19 by regulating cytokine responses and controlling glucose metabolism, which is implicated in the host immune response to SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Seong, Kim, Han, Seo, Hyun, Yoon, Nham, Noh, Cheong, Kim, Lim and Song.)

Background: Whether or not a single-dose Ad26.COV2.S prime and boost vaccination induces sufficient immunity is unclear. Concerns about the increased risk of breakthrough infections in the Ad26.COV2.S-primed population have also been raised., Methods: A prospective cohort study was conducted. Participants included healthy adults who were Ad26.COV2.S primed and scheduled to receive a booster vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. The IgG anti-receptor binding domain (RBD) antibody titers, neutralizing antibody (NAb) titers (against wild type [WT] and Omicron [BA.1 and BA.5]), and Spike-specific interferon-γ responses of the participants were estimated at baseline, 3-4 weeks, 3 months, and 6 months after booster vaccination., Results: A total of 89 participants were recruited (26 boosted with BNT162b2, 57 with mRNA-1273, and 7 with Ad26.COV2.S). The IgG anti-RBD antibody titers of all participants were significantly higher at 6 months post-vaccination than at baseline. The NAb titers against WT at 3 months post-vaccination were 359, 258, and 166 in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. Compared with those against WT, the NAb titers against BA.1/BA.5 were lower by 23.9/10.9-, 16.6/7.4-, and 13.8/7.2-fold in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively, at 3 months post-vaccination. Notably, the NAb titers against BA.1 were not boosted after Ad26.COV2.S vaccination. Breakthrough infections occurred in 53.8%, 62.5%, and 42.9% of the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. No significant difference in humoral and cellular immunity was found between individuals with and without SARS-CoV-2 breakthrough infections., Conclusion: Booster vaccination elicited acceptable humoral and cellular immune responses in Ad26.COV2.S-primed individuals. However, the neutralizing activities against Omicron subvariants were negligible, and breakthrough infection rates were remarkably high at 3 months post-booster vaccination, irrespective of the vaccine type. A booster dose of a vaccine containing the Omicron variant antigen would be required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hyun, Jang, Park, Heo, Seo, Nham, Yoon, Seong, Noh, Cheong, Kim, Yoon, Seok, Kim, Park and Song.)

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the persistence of the pandemic, even with mass coronavirus disease 2019 (COVID-19) vaccination, have raised questions about the durability of immunity and extent of cross-reactive immunity after vaccination. This study aimed to characterize the humoral and cellular immune response to the mRNA-1273 vaccine using a prospective longitudinal cohort., Methods: We recruited 177 young SARS-CoV-2 infection-naive adults. Two doses of mRNA-1273 vaccine were administered at 28-day intervals, and blood samples were collected at five time points: pre-vaccination (T0), 4 weeks after the first (T1) and second dose (T2), and 3 months (T3) and 6 months (T4) after the first dose. Anti-SARS-CoV-2 spike protein (anti-S) IgG antibody, neutralizing antibody, and T-cell immune responses were evaluated., Results: The two-dose mRNA-1273 vaccination induced robust anti-SARS-CoV-2 antibody responses, which remained higher than the titers at T1 until T4. A higher peak anti-S antibody titer at T2 was associated with better cross-reactive immunity against Delta and Omicron variants and long-lasting (anti-S IgG and neutralizing antibody) humoral immunity up to T4. The overall T-cell immune response was not correlated with peak antibody titers (T-lymphocyte subpopulation analysis was not performed)., Conclusion: This study showed that an early strong antibody response is predictive of longer humoral immunity and better cross-reactive neutralizing immunity against Delta and Omicron variants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Choi, Heo, Seo, Yoon, Sohn, Noh, Cheong, Kim, Choi, Kim, Lee, Lee, Kim, Kim and Song.)

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic since 2019. Variants of concern (VOCs) declared by the World Health Organization require continuous monitoring because of their possible changes in transmissibility, virulence, and antigenicity. The Omicron variant, a VOC, has become the dominant variant worldwide since November 2021. In the Republic of Korea (South Korea), the number of confirmed cases increased rapidly after the detection of Omicron VOC on November 24, 2021. In this study, we estimated the underlying epidemiological processes of Omicron VOC in South Korea using time-scaled phylodynamic analysis. Three distinct phylogenetic subgroups (Kor-O1, Kor-O2, and Kor-O3) were detected in South Korea. The Kor-O1 subgroup circulated in the Daegu region, whereas Kor-O2 and Kor-O3 circulated in Incheon and Jeollanam-do, respectively. The viral population size and case number of the Kor-O1 subgroup increased more rapidly than those of the other subgroups, indicating the rapid spread of the virus. The results indicated the multiple introductions of Omicron sub-lineages into South Korea and their subsequent co-circulation. The evolution and transmission of SARS-CoV-2 should be continuously monitored, and control strategies need to be improved to control the multiple variants., (© 2022. The Author(s).)

Since its first emergence in late 2019, severe acute respiratory syndrome coronavirus-2 has claimed more than 6.5 million lives worldwide and continues to infect hundreds of thousands of people daily. To combat this once-in-a-century disaster, several vaccines have been developed at unprecedented speeds. Novel vaccine platforms (messenger ribonucleic acid vaccines and adenoviral vector vaccines) have played a major role in the current pandemic. In Korea, six vaccines, including a domestically developed recombinant vaccine, have been approved. As in other countries, vaccines have been proven to be safe and highly effective in Korea. However, rare serious adverse events and breakthrough infections have undermined public trust in the vaccines, even while the benefits of vaccination far outweigh the risks. The rise of the omicron variant and the subsequent increase in excess mortality demonstrated that while vaccines are a key component of the pandemic response, it alone can fail without non-pharmaceutical interventions like masking and social distancing. The pandemic of coronavirus disease has revealed both the strengths and weaknesses of our healthcare system and pandemic preparedness. When the next pandemic arrives, improved risk communication and vaccine development should be prioritized. To enable timely vaccine development, it is essential to make strategic and sufficient investments in vaccine research and development., Competing Interests: All authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

As most individuals acquire immunity to severe acute respiratory syndrome coronavirus 2, South Korea declared a return to normalcy a few months ago. However, epidemic waves continue because of endlessly emerging variants and waning immunity. Health authorities are focusing on those at high risk of severe coronavirus disease 2019 to minimize damage to public health and the economy. In this regard, we investigated the vaccination rates in patients with various chronic medical conditions by examining the national health insurance claims data and the national immunization registry. We found that patients with chronic medical conditions, especially those of higher severity, such as malignancy, had vaccination rates approximately 10-20% lower than those of the general population. Public health authorities and healthcare providers should try to vaccinate these patients to avoid preventable morbidity and mortality., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 ( K18 ) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥10 5 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B ( SFTPB ) and secretoglobin family 1a member 1 ( Scgb1a1 ) promoters. After inoculation of 10 5 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Kim, Jang, Noh, Park, Jeong, Jeon, Uhm, Oh, Cho, Jeon, On, Yoon, Lim, Kim, Lee, Jang, Park, Oh, Seo, Kim, Seok, Lee, Hong, An, Kim, Kim, Hwang, Lee, Kim, Choi, Park, Seo, Yun, Shin, Lee, Kim, Lee, Lee, Nam and Seong.)

Omicron has become the globally dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. Compared with two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augments serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Early detection of new outbreak waves is critical for effective and sustained response to the COVID-19 pandemic. We conducted a growth rate analysis using local community and inpatient records from seven hospital systems to characterize distinct phases in SARS-CoV-2 outbreak waves in the Greater Houston area. We determined the transition times from rapid spread of infection in the community to surge in the number of inpatients in local hospitals. We identified 193,237 residents who tested positive for SARS-CoV-2 via molecular testing from April 8, 2020 to June 30, 2021, and 30,031 residents admitted within local healthcare institutions with a positive SARS-CoV-2 test, including emergency cases. We detected two distinct COVID-19 waves: May 12, 2020-September 6, 2020 and September 27, 2020-May 15, 2021; each encompassed four growth phases: lagging, exponential/rapid growth, deceleration, and stationary/linear. Our findings showed that, during early stages of the pandemic, the surge in the number of daily cases in the community preceded that of inpatients admitted to local hospitals by 12-36 days. Rapid decline in hospitalized cases was an early indicator of transition to deceleration in the community. Our real-time analysis informed local pandemic response in one of the largest U.S. metropolitan areas, providing an operationalized framework to support robust real-world surveillance for outbreak preparedness., (© 2022. The Author(s).)

A prospective cohort study was conducted for adults with a diagnosis of with coronavirus disease 2019 (COVID-19). Convalescent blood samples were obtained 4, 6, and 11 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The seropositivity of anti-spike antibody was maintained in all patients (100%) until 11 months after COVID-19 diagnosis. Neutralizing antibody levels against wild-type SARS-CoV-2 gradually decreased but remained positive in >50% of patients 11 months after diagnosis: in 98.5% (67 of 68) at 4 months, 86.8% (46 of 53) at 6 months, and 58.8% (40 of 68) at 11 months. However, cross-neutralizing activity against the Beta and Delta variants was attenuated 2.53-fold and 2.93-fold, respectively, compared with the wild-type strain., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to have high infectivity and is more likely to evade vaccine immunity. However, booster vaccination is expected to strengthen cross-reactive immunity, thereby increasing the vaccine effectiveness (VE). This study aimed to evaluate the relative VE of the 3-dose (booster) vaccination compared with the 2-dose primary series vaccination in healthcare workers during omicron variant-dominant periods. During the omicron-dominant period from February 1, 2022 to February 28, 2022, a 1:1 matched case-control study was conducted. Healthcare workers with positive SARS-CoV-2 test results were classified as positive cases, whereas those with negative results served as controls. Compared with the 2-dose primary series vaccination, booster vaccination with mRNA vaccine showed moderate VE (53.1%). However, in multivariate analysis including the time elapsed after vaccination, the significant VE disappeared, reflecting the impact of recent vaccination rather than the third dose itself., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1β levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Heo, Seo, Kim, Lee, Kim, Yoon, Noh, Cheong, Kim, Yoon, Choi, Lee, Lee, Kim, Kim and Song.)

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 can lead to acute respiratory distress syndrome. Awake venovenous extracorporeal membrane oxygenation is known to be effective in patients with critical COVID-19 and respiratory failure. This report describes the rehabilitation course and functional progress of a 63-year-old man who contracted severe COVID-19 and underwent awake venovenous extracorporeal membrane oxygenation. He started rehabilitation from the time of isolation while receiving venovenous extracorporeal membrane oxygenation and underwent a 30-day course of inpatient comprehensive rehabilitation. He regained functional independence and cognitive abilities and was able to walk without assistance at hospital discharge without any complications. This study demonstrates the feasibility of starting rehabilitation for COVID-19 early while the patient is on awake venovenous extracorporeal membrane oxygenation and eventually achieving a favorable outcome., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Face masks are used to protect the wearer from harmful external air and to prevent transmission of viruses from air exhaled by potentially infected wearers to the surrounding people. In this study, we examined the potential utility of masks for collecting viruses contained in exhaled breath and detected the collected viruses via various molecular tests. Using KF94 masks, the inner electrostatic filter was selected for virus collection, and an RNA extraction protocol was developed for the face mask. Virus detection in worn mask samples was performed using PCR and rolling circle amplification (RCA) tests and four different target genes (N, E, RdRp, and ORF1ab genes). The present study confirmed that the mask sample tests showed positive SARS-CoV-2 results, similar to the PCR tests using nasopharyngeal swab samples. In addition, the quantity of nucleic acid collected in the masks linearly increased with wearing time. These results suggest that samples for SARS-CoV-2 tests can be collected in a noninvasive, quick, and easy method by simply submitting worn masks from subjects, which can significantly reduce the hassle of waiting at airports or public places and concerns about cross-infection. In addition, it is expected that miniaturization technology will integrate PCR assays on face masks in the near future, and mask-based self-diagnosis would play a significant role in resolving the pandemic situation., Competing Interests: The authors have declared that no competing interests exist.

COVID-19 vaccines elicit humoral and cellular immune responses. Durable maintenance of vaccine-induced immunity is required for long-term protection of the host. Here, we examine activation and differentiation of vaccine-induced CD8 + T cells using MHC class I (MHC-I) multimers and correlations between early differentiation and the durability of CD8 + T cell responses among healthcare workers immunized with two doses of BNT162b2. The frequency of MHC-I multimer + cells is robustly increased by BNT162b2 but decreases 6 months post-second vaccination to 2.4%-65.6% (23.0% on average) of the peak. MHC-I multimer + cells dominantly exhibit phenotypes of activated effector cells 1-2 weeks post-second vaccination and gradually acquire phenotypes of long-term memory cells, including stem cell-like memory T (T SCM ) cells. Importantly, the frequency of T SCM cells 1-2 weeks post-second vaccination significantly correlates with the 6-month durability of CD8 + T cells, indicating that early generation of T SCM cells determines the longevity of vaccine-induced memory CD8 + T cell responses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is currently spreading globally. To overcome the COVID-19 pandemic, preclinical evaluations of vaccines and therapeutics using K18-hACE2 and CAG-hACE2 transgenic mice are ongoing. However, a comparative study on SARS-CoV-2 infection between K18-hACE2 and CAG-hACE2 mice has not been published. In this study, we compared the susceptibility and resistance to SARS-CoV-2 infection between two strains of transgenic mice, which were generated in FVB background mice. K18-hACE2 mice exhibited severe weight loss with definitive lethality, but CAG-hACE2 mice survived; and differences were observed in the lung, spleen, cerebrum, cerebellum, and small intestine. A higher viral titer was detected in the lungs, cerebrums, and cerebellums of K18-hACE2 mice than in the lungs of CAG-hACE2 mice. Severe pneumonia was observed in histopathological findings in K18-hACE2, and mild pneumonia was observed in CAG-hACE2. Atrophy of the splenic white pulp and reduction of spleen weight was observed, and hyperplasia of goblet cells with villi atrophy of the small intestine was observed in K18-hACE2 mice compared to CAG-hACE2 mice. These results indicate that K18-hACE2 mice are relatively susceptible to SARS-CoV-2 and that CAG-hACE2 mice are resistant to SARS-CoV-2. Based on these lineage-specific sensitivities, we suggest that K18-hACE2 mouse is suitable for highly susceptible model of SARS-CoV-2, and CAG-hACE2 mouse is suitable for mild susceptible model of SARS-CoV-2 infection., Competing Interests: The authors have declared that no competing interests exist.

Background: As the coronavirus disease 2019 (COVID-19) pandemic continues, there are concerns regarding waning immunity and the emergence of viral variants. The immunogenicity of Ad26.COV2.S against wild-type (WT) and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated., Method: This prospective cohort study was conducted between June 2021 and January 2022 at two university hospitals in South Korea. Healthy adults who were scheduled to be vaccinated with Ad26.COV2.S were enrolled in this study. The main outcomes included anti-spike (S) IgG antibody and neutralizing antibody responses, S-specific T-cell responses (interferon-γ enzyme-linked immunospot assay), solicited adverse events (AEs), and serious AEs., Results: Fifty participants aged ≥ 19 years were included in the study. Geometric mean titers (GMTs) of anti-S IgG were 0.4 U/mL at baseline, 5.2 ± 3.0 U/mL at 3-4 weeks, 55.7 ± 2.4 U/mL at 5-8 weeks, and 81.3 ± 2.5 U/mL at 10-12 weeks after vaccination. GMTs of 50% neutralizing dilution (ND50) against WT SARS-CoV-2 were 164.6 ± 4.6 at 3-4 weeks, 313.9 ± 3.6 at 5-8 weeks, and 124.4 ± 2.6 at 10-12 weeks after vaccination. As for the S-specific T-cell responses, the median number of spot-forming units/10 6 peripheral blood mononuclear cell was 25.0 (5.0-29.2) at baseline, 60.0 (23.3-178.3) at 5-8 weeks, and 35.0 (13.3-71.7) at 10-12 weeks after vaccination. Compared to WT SARS-CoV-2, ND50 against Delta and Omicron variants was attenuated by 3.6-fold and 8.2-fold, respectively. The most frequent AE was injection site pain (82%), followed by myalgia (80%), fatigue (70%), and fever (50%). Most AEs were grade 1-2, and resolved within two days., Conclusion: Single-dose Ad26.COV2.S was safe and immunogenic. NAb titer and S-specific T-cell immunity peak at 5-8 weeks and rather decrease at 10-12 weeks after vaccination. Cross-reactive neutralizing activity against the Omicron variant was negligible., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

The Omicron variant (B.1.1.529) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) extensively escapes neutralizing antibodies elicited by SARS-CoV-2 infection or vaccination. In the present study, we investigated whether BNT162b2 messenger RNA vaccine-induced memory T cells functionally respond to the Omicron spike protein. Experiments were performed using samples from healthcare workers who were immunized with two or three doses of the BNT162b2 mRNA vaccine and individuals with prior SARS-CoV-2 infection who were immunized with two doses of the BNT162b2 vaccine. Vaccine-induced memory T cells exhibited substantial responses to the Omicron spike protein, with no difference between healthcare workers with two versus three vaccine doses. In individuals with prior infection, two-dose vaccination robustly boosted memory T cells that responded to the Omicron spike protein and the SARS-CoV-2 wild-type (lineage B) spike protein. Importantly, polyfunctionality was preserved in vaccine-induced memory T cells responding to the Omicron spike protein. The present findings indicate that BNT162b2-induced memory T cells substantially respond to the Omicron variant with preserved polyfunctionality., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still continuing worldwide. Currently, two mRNA-based vaccines and two DNA vaccines using an adenovirus vector are representative vaccines. Since the SARS-CoV-2 vaccines began to be administered, a significant decrease in new infections and COVID-19-associated death has been reported. However, various adverse events from mild symptoms to death have also been described after vaccination., Case Description: Patients with high fever and lymphadenopathy who are diagnosed with hemophagocytic lymphohistiocytosis (HLH) after COVID-19 vaccination are very rare, and there is no standard management guideline for these patients thus far. Herein, we described two cases of HLH after the administration of an mRNA-based vaccine and adenovirus vector vaccine., Discussion: HLH is a life-threatening hyperinflammatory syndrome that occurs due to persistent stimulation of lymphocytes and histiocytes in various underlying conditions at all ages. Although the exact mechanisms and risk factors of COVID-19 vaccination-related HLH are still unknown, vigorous immune stimulation may trigger a huge cytokine storm, rarely resulting in HLH. It is important to note that early suspicion by clinicians can lower the mortality rate.

Background: The association of tracheostomy timing and clinical outcomes in ventilated COVID-19 patients remains controversial. We performed a meta-analysis to evaluate the impact of early tracheostomy compared to late tracheostomy on COVID-19 patients' outcomes., Methods: We searched Medline, Embase, Cochrane, and Scopus database, along with medRxiv, bioRxiv, and Research Square, from December 1, 2019, to August 24, 2021. Early tracheostomy was defined as a tracheostomy conducted 14 days or less after initiation of invasive mechanical ventilation (IMV). Late tracheostomy was any time thereafter. Duration of IMV, duration of ICU stay, and overall mortality were the primary outcomes of the meta-analysis. Pooled odds ratios (OR) or the mean differences (MD) with 95%CIs were calculated using a random-effects model., Results: Fourteen studies with a cumulative 2371 tracheostomized COVID-19 patients were included in this review. Early tracheostomy was associated with significant reductions in duration of IMV (2098 patients; MD - 9.08 days, 95% CI - 10.91 to - 7.26 days, p < 0.01) and duration of ICU stay (1224 patients; MD - 9.41 days, 95% CI - 12.36 to - 6.46 days, p < 0.01). Mortality was reported for 2343 patients and was comparable between groups (OR 1.09, 95% CI 0.79-1.51, p = 0.59)., Conclusions: The results of this meta-analysis suggest that, compared with late tracheostomy, early tracheostomy in COVID-19 patients was associated with shorter duration of IMV and ICU stay without modifying the mortality rate. These findings may have important implications to improve ICU availability during the COVID-19 pandemic. Trial registration The protocol was registered at INPLASY (INPLASY202180088)., (© 2022. The Author(s).)

Colorimetric sensors are recognized as a promising means for target molecule detection as they provide rapid, cost-effective, and facile sensing visible to the naked eye. Challenges remain though in terms of their detection sensitivity and specificity for short-length target genes. Herein, we demonstrate the successful combination of the catalytic hairpin DNA assembly (CHA) approach with enzyme-linked immunosorbent assay (ELISA)-mimicking techniques for a simple, sensitive, and sequence-specific colorimetric assay to detect short SARS-CoV-2 target cDNA. In the developed CHA-based chemiluminescent assay, a low concentration of target cDNA is continuously recycled to amplify dimeric DNA probes from two biotinylated hairpin DNA until the hairpin DNA is completely consumed. The dimeric DNA probes are effectively immobilized in a neutravidin-coated microplate well and then capture neutravidin-conjugated horseradish peroxidase via biotin-neutravidin interactions, resulting in a sensitive and selective colorless-to-blue color change. The developed sensing system exhibits a high sensitivity with a detection limit of ~1 nM for target cDNA as well as the ability to precisely distinguish a single-base mismatched mutant gene within 2 h. As the proposed system does not require complex protocols or expensive equipment to amplify target cDNA, it has the potential to be utilized as a powerful tool to improve the detection sensitivity of target genes for clinical diagnostics with colorimetric detection., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There is insufficient data on the longevity of immunity acquired after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: We aimed to evaluate the duration of SARS-CoV-2-specific humoral and cellular immunity according to the clinical severity of coronavirus disease 2019 (COVID-19). The study population comprised asymptomatic (n = 14), symptomatic/nonpneumonic (n = 42), and pneumonic (n = 41) patients., Results: The anti-SARS-CoV-2 immunoglobulin class G and neutralizing antibody (NAb) titers lasted until 6 months after diagnosis, with positivity rates of 66.7% and 86.9%, respectively. Older age, prolonged viral shedding, and accompanying pneumonia were more frequently found in patients with sustained humoral immunity. Severe acute respiratory syndrome coronavirus 2-specific T-cell response was strongly observed in pneumonic patients and prominent in individuals with sustained humoral immunity., Conclusions: In conclusion, most (>85%) patients carry NAb until 6 months after diagnosis of SARS-CoV-2 infection, providing insights for establishing vaccination strategies against COVID-19., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Since February 26, 2021, when vaccination against coronavirus disease 2019 (COVID-19) began in South Korea, patients who visited the Korea University Guro Hospital with suspected adverse events after COVID-19 vaccination were monitored actively with interest. We encountered five unusual cases of polyarthralgia and myalgia syndrome in patients who received the ChAdOx1 nCOV-19 (AstraZeneca) vaccine. The patients (median age 67 years) were not previously diagnosed with arthropathy and rheumatologic diseases. They developed fever, myalgia, joint pain, and swelling three to seven days after vaccination. The symptoms persisted for up to 47 days despite antipyretic treatment. Arthralgia occurred in multiple joints, including small and large joints. A whole-body Technetium-99m methylene diphosphonate bone scan revealed unusual uptakes in the affected joints. Non-steroidal anti-inflammatory drugs with or without prednisolone relieved the symptoms of all patients. Further monitoring is required to clarify the long-term prognosis of this syndrome., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Anecdotal evidence suggests that the severity of coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is likely to be distinguished by variations in loss of smell (LOS). Thus, we conducted a meta-analysis of 45 articles that include a total of 42,120 COVID-19 patients from 17 different countries to demonstrate that severely ill or hospitalized COVID-19 patients have a lesser chance of experiencing LOS than non-severely ill or non-hospitalized COVID-19 patients (odds ratio = 0.527 [95% CI 0.373-0.744; p < 0.001] and 0.283 [95% CI 0.173-0.462; p < 0.001], respectively). We also proposed a possible mechanism underlying the association of COVID-19 severity with anosmia, which may explain why patients without sense of smell develop severe COVID-19. Variations in LOS according to the severity of COVID-19 is a global phenomenon, with few exceptions. Since severely ill patients have a lower rate of anosmia, patients without anosmia should be monitored more closely in the early stages of COVID-19, for early diagnosis of severity of illness. An understanding of how the severity of COVID-19 infection and LOS are associated has profound implications for the clinical management and mitigation strategies for the disease., (© 2021. The Pharmaceutical Society of Korea.)

Hospital-based surveillance for adverse events was conducted on healthcare workers after they received the first dose of coronavirus disease 2019 (COVID-19) vaccine. Among the two new platform vaccines (messenger RNA- and adenoviral vector-based vaccines), the rates of systemic adverse events were significantly higher among adenovirus-vectored vaccine recipients. Fatigue (87.6% vs. 53.8%), myalgia (80.8% vs. 50.0%), headache (72.0% vs. 28.8%), and fever (≥ 38.0°C, 38.7% vs. 0%) were the most common adverse events among adenovirus-vectored vaccine recipients, but most symptoms resolved within 2 days. Both types of COVID-19 vaccines were generally safe, and serious adverse events rarely occurred., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Macrophages play an important role in the innate and adaptive immune responses of organ systems, including the lungs, to particles and pathogens. Cumulative results show that macrophages contribute to the development and progression of acute or chronic inflammatory responses through the secretion of inflammatory cytokines/chemokines and the activation of transcription factors in the pathogenesis of inflammatory lung diseases, such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), ARDS related to COVID-19 (coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), allergic asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). This review summarizes the functions of macrophages and their associated underlying mechanisms in the development of ALI, ARDS, COVID-19-related ARDS, allergic asthma, COPD, and IPF and briefly introduces the acute and chronic experimental animal models. Thus, this review suggests an effective therapeutic approach that focuses on the regulation of macrophage function in the context of inflammatory lung diseases.

The Republic of Korea (ROK) experienced a public health crisis due to Middle East respiratory syndrome (MERS) in 2015 and is currently going through the coronavirus disease 2019 (COVID-19) pandemic. Lessons learned from the disastrous MERS outbreak were ref lected in the preparedness system, and the readiness capabilities that were subsequently developed enabled the country to successfully flatten the epidemic curve of COVID-19 in late February and March 2020. In this review, we summarize and compare the epidemiology and response of the ROK to the 2015 MERS outbreak and the COVID-19 epidemic in early 2020. We emphasize that, because further COVID-19 waves seem inevitable, it is urgent to develop comprehensive preparedness and response plans for the worst-case scenarios of the COVID-19 pandemic. Simultaneously strengthening healthcare capacity to endure the peak demand and implementing smart strategies to sustain social distancing and public hygiene are necessary until safe and effective therapeutics and vaccines against COVID-19 are available.

Objectives: To compare epidemiologic features of the second and third waves of the coronavirus disease 2019 (COVID-19) pandemic in South Korea., Methods: Nationwide COVID-19 data were collected between 6 May and 30 December 2020. The degree of social activity was estimated using an Internet search trend analysis program for leisure-related keywords, including 'eating-out', 'trip' and 'get directions' (transportation). Demographics, transmission chains, case fatality rates, social activity levels and public health responses were compared between the second (13 August-18 September 2020) and third (4 November 2020-present) waves., Results: In comparison with the second wave, the third wave was characterized by delayed strengthening of social distancing policies (3 vs. 15 days), longer duration (36 vs. >56 days) and a higher case fatality rate (0.91% vs. 1.26%). There were significant differences in transmission chains between the second and third waves (P < 0.01). In comparison with the second wave, the proportion of local clusters (24.8% vs. 45.7%) was lower in the third wave, and personal contact transmission (38.5% vs. 25.9%) and unknown routes of transmission (23.5% vs. 20.8%) were higher in the third wave., Conclusion: Early and timely interventions with strengthened social distancing policies should be implemented to suppress and control the COVID-19 pandemic effectively., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The quarantine process at a country's port of entry has an important role in preventing an influx of coronavirus disease 2019 (COVID-19) cases from abroad and further minimizing the national healthcare burden of COVID-19. However, there has been little published on the process of COVID-19 screening among travelers entering into a country. Identifying the characteristics of COVID-19 infected travelers could help attenuate the further spread of the disease., Methods: The authors analyzed epidemiological investigation forms and real-time polymerase chain reaction (PCR) results for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of entrants to Incheon International Airport between March 11 to April 30, 2020. We performed univariate and multivariate logistic regression analysis to determine the odds of positive SARS-CoV-2 result., Results: A total of 11,074 entrants underwent reverse-transcription PCR for SARS-CoV-2, resulting 388 confirmed cases of COVID-19 infection. COVID-19 had a strong association with the reported loss of smell or taste and association with self-reported fever, chill, cough, and vomiting. If a traveler reported contact with an individual with either respiratory symptoms or confirmed COVID-19 in the last two weeks directly prior to landing, the probability of a positive result was increased., Conclusion: If overseas travelers experience loss of smell or taste in the two weeks prior to arrival, they may require an immediate examination to rule out COVID-19 at a port of entry. As to measure body temperature upon arrival at a port of entry, it is important to screen for any occurrence of fever within the two weeks prior to travel. Also, information with epidemiological relevance, such as recent contact with an individual suffering from any respiratory symptoms or with confirmed COVID-19, should be included in COVID-19 screening questionnaires for international travelers., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Erythema nodosum (EN) is a skin manifestation of panniculitis characterized by symmetric, painful, tender nodules, and most cases are self-limiting. Few cases of EN following Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination have been reported, and they are generally self-limiting. We reported the challenging case of a 63-year-old Asian woman with EN that persisted for more than three months after a coronavirus disease-19 (COVID-19). There was no improvement despite topical steroid and NSAIDs treatment, and the patient was successfully treated with combination of high-dose steroid and NSAIDs. There were long-lasting symptoms involving various organ symptoms persisting over three months after COVID-19, which is known as Long COVID. As part of Long COVID, there are limited cases of skin manifestations. Given that immune dysregulation due to persistent coronaviruses may contribute to refractory EN, Erythema nodosum related to COVID-19 is rare, but can occur; clinicians should be aware of the occurrence of EN following COVID-19 infection.

As coronavirus disease-2019 (COVID-19) becomes an endemic disease, the virus continues to evolve and become immunologically distinct from previous strains. Immune imprinting has raised concerns about bivalent mRNA vaccines containing both ancestral virus and Omicron variant. To increase efficacy against the predominant strains as of the second half of 2023, the updated vaccine formulation contained only the mRNA of XBB.1.5 sublineage. We conducted a multicenter, test-negative, case-control study to estimate XBB.1.5 monovalent vaccine effectiveness (VE) and present the results of an interim analysis with data collected in November 2023. Patients who underwent COVID-19 testing at eight university hospitals were included and matched based on age (19-49, 50-64, and ≥65 years) and sex in a 1:1 ratio. VE was calculated using the adjusted odds ratio derived from multivariable logistic regression. Of the 992 patients included, 49 (5.3%) received the XBB.1.5 monovalent vaccine at least 7 days before COVID-19 testing. Patients with COVID-19 (cases) were less likely to have received the XBB.1.5 monovalent vaccine (case 3.5% vs. control 7.2%, p=0.019) and to have a history of COVID-19 within 6 months (2.2% vs. 4.6%, p=0.068). In contrast, patients with COVID-19 were more likely to be healthcare workers (8.2% vs. 3.0%, p=0.001) and to have chronic neurological diseases (16.7% vs. 11.9%, p=0.048). The adjusted VE of the XBB.1.5 monovalent mRNA vaccine was 56.8% (95% confidence interval: 18.7-77.9%). XBB.1.5 monovalent mRNA vaccine provided significant protection against COVID-19 in the first one to two months after vaccination.

Coronavirus disease 2019 (COVID-19) is a highly contagious zoonotic respiratory disease with many similarities to influenza. Effective vaccines are available for both; however, rapid viral evolution and waning immunity make them virtually impossible to eradicate with vaccines. Thus, the practical goal of vaccination is to reduce the incidence of serious illnesses and death. Three years after the introduction of COVID-19 vaccines, the optimal vaccination strategy in the endemic period remains elusive, and health authorities worldwide have begun to adopt various approaches. Herein, we propose a COVID-19 vaccination strategy based on the data available until early 2024 and discuss aspects that require further clarification for better decision making. Drawing from comparisons between COVID-19 and influenza vaccination strategies, our proposed COVID-19 vaccination strategy prioritizes high-risk groups, emphasizes seasonal administration aligned with influenza vaccination campaigns, and advocates the co-administration with influenza vaccines to increase coverage.