An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study

The Lancet, Journal Year: 2020, Volume and Issue: 395(10239), P. 1771 - 1778

Published: May 13, 2020

BackgroundThe Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, a natural observatory of virus manifestations in general population. In past month we recorded an outbreak Kawasaki disease; aimed to evaluate incidence and features patients with Kawasaki-like disease diagnosed during SARS-CoV-2 epidemic.MethodsAll at our centre 5 years were divided according symptomatic presentation before (group 1) or after 2) beginning epidemic. Kawasaki- like presentations managed as American Heart Association indications. shock (KDSS) was defined presence circulatory dysfunction, macrophage activation (MAS) Paediatric Rheumatology International Trials Organisation criteria. Current previous infection sought reverse-transcriptase quantitative PCR nasopharyngeal oropharyngeal swabs, serological qualitative test detecting IgM IgG, respectively.FindingsGroup 1 comprised 19 (seven boys, 12 girls; aged 3·0 [SD 2·5]) between Jan 1, 2015, Feb 17, 2020. Group included ten three 7·5 3·5]) 18 April 20, 2020; eight positive for IgG IgM, both. The two groups differed vs group 2, 0·3 per month), mean age (3·0 years), cardiac involvement (two six ten), KDSS (zero five MAS need adjunctive steroid treatment (three ten; all p<0·01).InterpretationIn found 30-fold increased disease. Children epidemic began showed evidence immune response virus, older, had higher rate involvement, MAS. associated high form A similar expected countries involved epidemic.FundingNone.

Language: Английский

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Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Dec. 9, 2020

Abstract Anecdotal evidence suggests that Coronavirus disease 2019 (COVID-19), caused by the coronavirus SARS-CoV-2, exhibits differences in morbidity and mortality between sexes. Here, we present a meta-analysis of 3,111,714 reported global cases to demonstrate that, whilst there is no difference proportion males females with confirmed COVID-19, male patients have almost three times odds requiring intensive treatment unit (ITU) admission (OR = 2.84; 95% CI 2.06, 3.92) higher death 1.39; 1.31, 1.47) compared females. With few exceptions, sex bias observed COVID-19 worldwide phenomenon. An appreciation how influencing outcomes will important implications for clinical management mitigation strategies this disease.

Language: Английский

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Severe Covid-19

New England Journal of Medicine, Journal Year: 2020, Volume and Issue: 383(25), P. 2451 - 2460

Published: May 15, 2020

Key Clinical Points Evaluation and Management of Severe Covid-19 Patients with severe coronavirus disease 2019 (Covid-19) may become critically ill acute respiratory distress syndrome that typ...

Language: Английский

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T cell responses in patients with COVID-19

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 20(9), P. 529 - 536

Published: July 29, 2020

Language: Английский

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Presence of Genetic Variants Among Young Men With Severe COVID-19

JAMA, Journal Year: 2020, Volume and Issue: 324(7), P. 663 - 663

Published: July 24, 2020

Severe coronavirus disease 2019 (COVID-19) can occur in younger, predominantly male, patients without preexisting medical conditions. Some individuals may have primary immunodeficiencies that predispose to severe infections caused by acute respiratory syndrome 2 (SARS-CoV-2).To explore the presence of genetic variants associated with among young COVID-19.Case series pairs brothers history meeting selection criteria (age <35 years) brother admitted intensive care unit (ICU) due COVID-19. Four men from unrelated families were ICUs 4 hospitals Netherlands between March 23 and April 12, 2020. The final date follow-up was May 16, Available family members included for variant segregation analysis as controls functional experiments.Severe COVID-19.Results rapid clinical whole-exome sequencing, performed identify a potential monogenic cause. Subsequently, basic immunological tests immune cells isolated characterize any defects.The male had mean age 26 years (range, 21-32), no major chronic disease. They previously well before developing insufficiency COVID-19, requiring mechanical ventilation ICU. duration ventilatory support 10 days 9-11); ICU stay 13 10-16). One patient died. Rapid sequencing available identified loss-of-function X-chromosomal TLR7. In 1, maternally inherited 4-nucleotide deletion (c.2129_2132del; p.[Gln710Argfs*18]); affected carried missense (c.2383G>T; p.[Val795Phe]). peripheral blood mononuclear patients, downstream type I interferon (IFN) signaling transcriptionally downregulated, measured significantly decreased mRNA expression IRF7, IFNB1, ISG15 on stimulation TLR7 agonist imiquimod compared controls. production IFN-γ, II IFN, response imiquimod.In this case rare putative impaired IFN responses. These preliminary findings provide insights into pathogenesis

Language: Английский

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Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients

BMC Infectious Diseases, Journal Year: 2021, Volume and Issue: 21(1)

Published: Aug. 21, 2021

Abstract Background Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. The impact several risk factors on mortality has been previously reported in meta‐analyses limited by small sample sizes. In this systematic review, we aimed summarize available findings association between comorbidities, complications, smoking status, obesity, gender, age and D-dimer, from COVID-19 using a large dataset number studies. Method Electronic databases including Google Scholar, Cochrane Library, Web Sciences (WOS), EMBASE, Medline/PubMed, Research Database, Scopus, were systematically searched till 31 August 2020. We included all human studies regardless language, publication date or region. Forty-two with total 423,117 patients met inclusion criteria. To pool estimate, mixed-effect model was used. Moreover, bias sensitivity analysis evaluated. Results consistent stating contribution age, acute kidney injury, D-dimer as factor increase requirement for advanced medical care. results showed that pooled prevalence among hospitalized 17.62% (95% CI 14.26–21.57%, 42 patients). Older shown increased due odds ratio (pOR) hazard (pHR) 2.61 1.75–3.47) 1.31 1.11–1.51), respectively. A significant found male (pOR = 1.45; 95% 1.41–1.51; pHR 1.24; 1.07–1.41), current smoker 1.42; 1.01–1.83). Furthermore, is highly influenced Chronic Obstructive Pulmonary Disease (COPD), Cardiovascular (CVD), diabetes, hypertension, obese, cancer, injury D-dimer. Conclusion demographic variables COPD, CVD, older smoker, obesity are clinical fatal outcome associated coronavirus. could be used disease’s future research, control prevention.

Language: Английский

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The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity

The Lancet Respiratory Medicine, Journal Year: 2021, Volume and Issue: 9(6), P. 622 - 642

Published: May 7, 2021

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into epidemiology of COVID-19, important questions remain about clinical complexities and underlying mechanisms disease phenotypes. Severe most commonly involves respiratory manifestations, although other systems are also affected, acute is often followed by protracted complications. Such complex manifestations suggest dysregulates host response, triggering wide-ranging immuno-inflammatory, thrombotic, parenchymal derangements. We review intricacies pathophysiology, its various phenotypes, anti-SARS-CoV-2 response at humoral cellular levels. Some similarities exist between failure origins, but evidence for many distinctive mechanistic features indicates constitutes a new entity, emerging data suggesting involvement an endotheliopathy-centred pathophysiology. Further research, combining basic studies, needed advance understanding pathophysiological characterise immuno-inflammatory derangements across range phenotypes enable optimum care patients COVID-19.

Language: Английский

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Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(11), P. 6141 - 6150

Published: Aug. 7, 2020

Convalescent plasma is a leading treatment for coronavirus disease 2019 (COVID-19), but there paucity of data identifying its therapeutic efficacy. Among 126 potential convalescent donors, the humoral immune response was evaluated using severe acute respiratory syndrome 2 (SARS–CoV-2) virus neutralization assay with Vero-E6-TMPRSS2 cells; commercial IgG and IgA ELISA to detect spike (S) protein S1 domain (EUROIMMUN); IgA, IgG, IgM indirect ELISAs full-length S or receptor–binding (S-RBD); an avidity assay. We used multiple linear regression predictive models assess correlations between antibody responses demographic clinical characteristics. titers were greater than either S1, S, S-RBD in overall population. Of samples, 101 (80%) had detectable neutralizing (nAb) titers. Using nAb as reference, confirmed 95%–98% nAb-positive 20%–32% nAb-negative samples still positive. Male sex, older age, hospitalization COVID-19 associated increased across serological assays. There substantial heterogeneity among emerged factors that can be identify individuals high likelihood having strong antiviral responses.

Language: Английский

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TMPRSS2 and COVID-19: Serendipity or Opportunity for Intervention?

Cancer Discovery, Journal Year: 2020, Volume and Issue: 10(6), P. 779 - 782

Published: April 10, 2020

TMPRSS2 is both the most frequently altered gene in primary prostate cancer and a critical factor enabling cellular infection by coronaviruses, including SARS-CoV-2. The modulation of its expression sex steroids could contribute to male predominance severe infections, given that has no known indispensable functions, inhibitors are available, it an appealing target for prevention or treatment respiratory viral infections.

Language: Английский

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X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

Science Immunology, Journal Year: 2021, Volume and Issue: 6(62)

Published: Aug. 10, 2021

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort 1,202 patients 0.5 99 52.9 with unexplained pneumonia. None the 331 asymptomatically or mildly infected 1.3 102 38.7 tested carry such (p = 3.5 × 10-5). The phenotypes five hemizygous relatives index cases SARS-CoV-2 include asymptomatic mild infection (n=2, 5 38 years), moderate (n=1, severe 27 29 Two boys (aged 12 262 51.0 are for variant. cumulative allele frequency general population is < 6.5x10-4 also show that blood B cell lines myeloid subsets do not respond stimulation, phenotype rescued by wild-type patients' plasmacytoid dendritic cells (pDCs) produce low levels IFNs response SARS-CoV-2. Overall, recessive deficiency highly penetrant genetic etiology pneumonia, about 1.8% below age 60 years. Human pDCs essential protective respiratory tract.

Language: Английский

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