Longitudinal Analysis of Memory T-Cell Responses in Survivors of Middle East Respiratory Syndrome.

BACKGROUND: Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a zoonotic betacoronavirus. The development of effective vaccines and control measures requires a thorough understanding of the immune response to this viral infection. METHODS: We investigated cellular immune responses up to 5 years after infection in a cohort of 59 MERS survivors by performing enzyme-linked immunospot assay and intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with synthetic viral peptides. RESULTS: Memory T-cell responses were detected in 82%, 75%, 69%, 64%, and 64% of MERS survivors from 1-5 years post-infection, respectively. Although the frequency of virus-specific interferon gamma (IFN-γ)-secreting T cells tended to be higher in moderately/severely ill patients than in mildly ill patients during the early period of follow-up, there was no significant difference among the different clinical severity groups across all time points. While both CD4+ and CD8+ T cells were involved in memory T-cell responses, CD4+ T cells persisted slightly longer than CD8+ T cells. Both memory CD4+ and CD8+ T cells recognized the E/M/N proteins better than the S protein and maintained their polyfunctionality throughout the period examined. Memory T-cell responses correlated positively with antibody responses during the initial 3-4 years but not with maximum viral loads at any time point. CONCLUSIONS: These findings advance our understanding of the dynamics of virus-specific memory T-cell immunity after MERS-coronavirus infection, which is relevant to the development of effective T cell-based vaccines.

A framework for nationwide COVID-19 vaccine safety research in the Republic of Korea: the COVID-19 Vaccine Safety Research Committee.

With the introduction of coronavirus disease 2019 (COVID-19) vaccines, the Korea Disease Control and Prevention Agency (KDCA) commissioned the National Academy of Medicine of Korea to gather experts to independently assess post-vaccination adverse events. Accordingly, the COVID-19 Vaccine Safety Research Committee (CoVaSC) was launched in November 2021 to perform safety studies and establish evidence for policy guidance. The CoVaSC established 3 committees for epidemiology, clinical research, and communication. The CoVaSC mainly utilizes pseudonymized data linking KDCA's COVID-19 vaccination data and the National Health Insurance Service's claims data. The CoVaSC's 5-step research process involves defining the target diseases and organizing ad-hoc committees, developing research protocols, performing analyses, assessing causal relationships, and announcing research findings and utilizing them to guide compensation policies. As of 2022, the CoVaSC completed this research process for 15 adverse events. The CoVaSC launched the COVID-19 Vaccine Safety Research Center in September 2022 and has been reorganized into 4 divisions to promote research including international collaborative studies, long-/short-term follow-up studies, and education programs. Through these enhancements, the CoVaSC will continue to swiftly provide scientific evidence for COVID-19 vaccine research and compensation and may serve as a model for preparing for future epidemics of new diseases.

Association of HLA class I and II genes with Middle East respiratory syndrome coronavirus infection in Koreans.

INTRODUCTION: Middle East Respiratory Syndrome (MERS) caused by MERS-coronavirus (CoV) is a lower respiratory tract disease characterized by a high mortality rate. MERS-CoV spread from Saudi Arabia to other countries, including South Korea. Dysfunction of the human leukocyte antigen (HLA) system has many effects due to genetic complexity and its role in the adaptive immune response. We investigated the association of HLA class I and II alleles with MERS-CoV in 32 patients with MERS. METHODS: HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 were genotyped by polymerase chain reaction sequence-based typing. RESULTS: HLA-DQB1*03:02 are significantly associated with moderate/mild cases of MERS-CoV. Other alleles are no statistical significance. CONCLUSIONS: Treatment strategies based on current research on the HLA gene and MERS-CoV will provide potential therapeutic targets.

Sustained Responses of Neutralizing Antibodies Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Recovered Patients and Their Therapeutic Applicability.

BACKGROUND: Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap. METHODS: We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge. RESULTS: Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (> 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss. CONCLUSIONS: High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.

Empirical Treatment and Prevention of COVID-19.

The rapid spread of severe acute respiratory coronavirus syndrome 2 (SARS-CoV-2) in the population and throughout the cells within our body has been developing. Another major cycle of coronavirus disease 2019 (COVID-19), which is expected in the coming fall, could be even more severe than the current one. Therefore, effective countermeasures should be developed based on the already obtained clinical and research information about SARS-CoV-2. The aim of this review was to summarize the data on the empirical treatment of COVID-19 acquired during this SARS-CoV-2 infection cycle; this would aid the establishment of an appropriate healthcare policy to meet the challenges in the future. The infectious disease caused by SARS-CoV-2 is characterized by common cold along with hypersensitivity reaction. Thus, in addition to treating common cold, it is essential to minimize the exposure of cells to the virus and to mitigate the uncontrolled immune response. A proper combination of antiviral agents, immune modulators such as prednisolone, and anticoagulants such as heparin and anti-C5a antagonists could be employed to minimize lung damage and prevent systemic involvements. Finally, strategies to achieve population immunity against SARS-CoV-2 should be developed through understanding of the interaction between the immune system and the virus.

Empirical Treatment and Prevention of COVID-19

The rapid spread of severe acute respiratory coronavirus syndrome 2 (SARS-CoV-2) in the population and throughout the cells within our body has been developing. Another major cycle of coronavirus disease 2019 (COVID-19), which is expected in the coming fall, could be even more severe than the current one. Therefore, effective countermeasures should be developed based on the already obtained clinical and research information about SARS-CoV-2. The aim of this review was to summarize the data on the empirical treatment of COVID-19 acquired during this SARS-CoV-2 infection cycle;this would aid the establishment of an appropriate healthcare policy to meet the challenges in the future. The infectious disease caused by SARS-CoV-2 is characterized by common cold along with hypersensitivity reaction. Thus, in addition to treating common cold, it is essential to minimize the exposure of cells to the virus and to mitigate the uncontrolled immune response. A proper combination of antiviral agents, immune modulators such as prednisolone, and anticoagulants such as heparin and anti-C5a antagonists could be employed to minimize lung damage and prevent systemic involvements. Finally, strategies to achieve population immunity against SARS-CoV-2 should be developed through understanding of the interaction between the immune system and the virus.