Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection

Shin, Hyoung-Shik; Kim, Yeonjae; Kim, Gayeon; Lee, Ji Yeon; Jeong, Ina; Joh, Joon Sung; Kim, Hana; Chang, Eunjin; Sim, Soo Yeon; Park, Jun-Sun; Lim, Dhongil

doi:10.1093/cid/ciy595

Cited by 140 publications

(155 citation statements)

References 34 publications

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“…[54][55][56] During the acute phase of MERS, robust virus-specific CD8 T-cell responses were detected in most patients with severe or moderate disease, with antibody and CD4 T-cell responses appearing later in the disease course. 57 T-cell and antibody responses were reliably detected 2-3 weeks after diagnosis, although they were detected earlier in some patients. 49,57 Studies of MERS survivors showed that MERS-CoV-specific antibody responses tended to be lower and transient in patients with mild or subclinical disease when compared with patients with severe disease, in whom MERS-CoV-specific antibody responses were detected for at least 2 years.…”

Section: Protective and Deleterious Immune Responsesmentioning

confidence: 90%

“…57 T-cell and antibody responses were reliably detected 2-3 weeks after diagnosis, although they were detected earlier in some patients. 49,57 Studies of MERS survivors showed that MERS-CoV-specific antibody responses tended to be lower and transient in patients with mild or subclinical disease when compared with patients with severe disease, in whom MERS-CoV-specific antibody responses were detected for at least 2 years. [57][58][59][60] In contrast, T-cell responses were detected in all MERS survivors for at least 2 years.…”

Section: Protective and Deleterious Immune Responsesmentioning

confidence: 90%

“…49,57 Studies of MERS survivors showed that MERS-CoV-specific antibody responses tended to be lower and transient in patients with mild or subclinical disease when compared with patients with severe disease, in whom MERS-CoV-specific antibody responses were detected for at least 2 years. [57][58][59][60] In contrast, T-cell responses were detected in all MERS survivors for at least 2 years. 59 The transitory nature of the antibody response in mild disease and greater stability of the T-cell response suggest that induction of both will be required for optimal longterm protection; the measurement of both will enhance the accuracy of prevalence studies.…”

Section: Protective and Deleterious Immune Responsesmentioning

confidence: 99%

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Middle East respiratory syndrome

et al. 2020

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The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.

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Section: Protective and Deleterious Immune Responsesmentioning

confidence: 90%

Section: Protective and Deleterious Immune Responsesmentioning

confidence: 90%

Section: Protective and Deleterious Immune Responsesmentioning

confidence: 99%

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Middle East respiratory syndrome

et al. 2020

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“…According to the statistics provided by the World Health Organization (WHO) on June 10, 2019, a total of 2428 laboratory-confirmed cases of human MERS-CoV infection have been reported, with an estimated 838 deaths in 27 countries. The accumulated evidence suggested that MERS-CoV infections are characterized by high levels of systemic inflammatory cytokines/chemokines as well as immunopathology [4][5][6][7][8][9][10][11]. High inflammatory cytokines and chemokines levels have been strongly correlated with poor disease outcomes, immunopathology and massive infiltration of the immune inflammatory cells into the lungs [10,12].…”

Section: Introductionmentioning

confidence: 99%

MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract

et al. 2020

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A B S T R A C TMERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4 + T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT 2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies.

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“…Airway memory T‐cells and viral E protein mutations have been identified in CoV infections as potential targets for vaccine strategies . Immune responses seem to be indicative of disease severity but more studies are needed to have a practical assay for decision making at hand.…”

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confidence: 99%