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Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses.

ABSTRACT: Coronaviruses (CoVs) are a large family of enveloped, positive-strand RNA viruses. Four human CoVs (HCoVs), the non-severe acute respiratory syndrome (SARS)-like HCoVs (namely HCoV 229E, NL63, OC43, and HKU1), are globally endemic and account for a substantial fraction of upper respiratory tract infections. Non-SARS-like CoV can occasionally produce severe diseases in frail subjects but do not cause any major (fatal) epidemics. In contrast, SARS like CoVs (namely SARS-CoV and Middle-East respiratory syndrome coronavirus, MERS-CoV) can cause intense short-lived fatal outbreaks. The current epidemic caused by the highly contagious SARS-CoV-2 and its rapid spread globally is of major concern. There is scanty knowledge on the actual pandemic potential of this new SARS-like virus. It might be speculated that SARS-CoV-2 epidemic is grossly underdiagnosed and that the infection is silently spreading across the globe with two consequences: (i) clusters of severe infections among frail subjects could haphazardly occur linked to unrecognized index cases; (ii) the current epidemic could naturally fall into a low-level endemic phase when a significant number of subjects will have developed immunity. Understanding the role of paucisymptomatic subjects and stratifying patients according to the risk of developing severe clinical presentations is pivotal for implementing reasonable measures to contain the infection and to reduce its mortality. Whilst the future evolution of this epidemic remains unpredictable, classic public health strategies must follow rational patterns. The emergence of yet another global epidemic underscores the permanent challenges that infectious diseases pose and underscores the need for global cooperation and preparedness, even during inter-epidemic periods.

SUBMITTER: Raoult D

PROVIDER: S-EPMC7146059 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses.

Raoult Didier D Zumla Alimuddin A Locatelli Franco F Ippolito Giuseppe G Kroemer Guido G

Cell stress 20200302 4

Coronaviruses (CoVs) are a large family of enveloped, positive-strand RNA viruses. Four human CoVs (HCoVs), the non-severe acute respiratory syndrome (SARS)-like HCoVs (namely HCoV 229E, NL63, OC43, and HKU1), are globally endemic and account for a substantial fraction of upper respiratory tract infections. Non-SARS-like CoV can occasionally produce severe diseases in frail subjects but do not cause any major (fatal) epidemics. In contrast, SARS like CoVs (namely SARS-CoV and Middle-East respira ...[more]

PMID: 32292881

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Project description:BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).

Project description:To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8+ T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8+ T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8+ T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.

Project description:Norovirus (NoV) is recognized as the second most important etiological agent leading to acute gastroenteritis globally. In order to determine the burden and characteristics of NoV infections in children in Qatar, profiling of circulating genotypes and their correlation with demographics and clinical manifestations were evaluated. A total of 177 NoV-positive fecal samples were collected from children suffering from acute gastroenteritis (AGE) during two-year period between June 2016 and June 2018. The age of the subjects ranged between 3 months and 12 years (median of 15 months). Genotyping was performed by amplifying and sequencing parts of viral VP1 and RNA-dependent RNA polymerase (RdRp) regions. Phylogenetic analysis and evolutionary relationships were performed using MEGA7.0. Fisher's exact test was used to run statistical analysis for the clinical and demographical characteristics of circulating strains. Overall, NoV infections were relatively higher in males than females with a ratio of 1.3:1 (p = 0.0073). Most of the NoV infections were reported in children between 1 and 3 years old (49.7%), followed by those <1 and >3 years of age (41.2% and 9.1%, respectively). NoV infections occurred throughout the year, with a noticeable increase in summer (36.6%) and drop in winter (25.4%). Nearly all (98.8%) NoV-infected children were positive for genogroup II (GII) compared to only two samples (1.2%) being positive for genogroup I (GI): GI.3 and GI.4. NoV genotype GII.4 (62.2%), GII.2 (15.8%), and GII.3 (13.5%) were predominant in our study. The detected strains shared >98% sequence homology with emerging recombinant strain of GII.P16-GII.4/RUS/Novosibirsk/2017 (MG892929), GII.P16-GII.4 Sydney/2012 (KY887601), GII.4 Sydney/2012, recombinant GII.P4 New Orleans /2009/GII.4 Sydney 2012 (MG585810.1), and the emerging strain GII.P16-GII.2 CHN/2017 (MH321823). Severe clinical illness (vesikari score >10) was reported in children infected with genotypes sharing homology with the above emerging strains. While GII.4 was reported in all age groups, NoV GII.3 infections were higher in children <1 year of age. Both genogroups (GII.4 and GII.3) in addition to GII.2 reported higher incidence in Qatari subjects compared to other nationalities (p = 0.034). This is the first report about NoV molecular epidemiology in Qatar. The most detected NoV strain was genogroup GII, which is the dominant genotype in the Middle East region. Further, we report GII.4, GII.2, and GII.3 as the most predominant NoV genotypes in our study. Moreover, disease severity scores were higher among children genotyped with genogroup GI (GI.4) and genogroup GII (GII.4, GII.2, GII.3, GII.6, and GII.7).

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Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses.

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Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses.

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