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1.
Genet Med ; 24(8): 1653-1663, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1819495

ABSTRACT

PURPOSE: Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants - referred as qualifying variants (QVs) - of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. METHODS: Exploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19. RESULTS: We found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue. CONCLUSION: This study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/.


Subject(s)
COVID-19 , Aged , COVID-19/genetics , Collectins/genetics , Collectins/metabolism , Germ Cells , Humans , Lectins/genetics , SARS-CoV-2 , Whole Exome Sequencing
2.
Front Immunol ; 13: 845496, 2022.
Article in English | MEDLINE | ID: covidwho-1775678

ABSTRACT

Background: Severe skeletal muscle damage has been recently reported in patients with SARS-CoV-2 infection and as a rare vaccination complication. Case summary: On Apr 28, 2021 a 68-year-old man who was previously healthy presented with an extremely severe rhabdomyolysis that occurred nine days following the first dose of SARS-CoV-2 ChAdOx1 nCov-19 vaccination. He had no risk factors, and denied any further assumption of drugs except for fermented red rice, and berberine supplement. The clinical scenario was complicated by a multi organ failure involving bone marrow, liver, lung, and kidney. For the rapid increase of the inflammatory markers, a cytokine storm was suspected and multi-target biologic immunosuppressive therapy was started, consisting of steroids, anakinra, and eculizumab, which was initially successful resulting in close to normal values of creatine phosphokinase after 17 days of treatment. Unfortunately, 48 days after the vaccination an accelerated phase of deterioration, characterized by severe multi-lineage cytopenia, untreatable hypotensive shock, hypoglycemia, and dramatic increase of procalcitonin (PCT), led to patient death. Conclusion: Physicians should be aware that severe and fatal rhabdomyolysis may occur after SARS-CoV2 vaccine administration.


Subject(s)
COVID-19 , Rhabdomyolysis , Thrombocytopenia , Aged , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Humans , Male , Multiple Organ Failure/etiology , RNA, Viral , Rhabdomyolysis/etiology , SARS-CoV-2 , Vaccination/adverse effects
3.
International Journal of Molecular Sciences ; 23(7):3450, 2022.
Article in English | MDPI | ID: covidwho-1762137

ABSTRACT

Pregnancy is characterized by significant immunological changes and a cytokine profile, as well as vitamin deficiencies that can cause problems for the correct development of a fetus. Defensins are small antimicrobial peptides that are part of the innate immune system and are involved in several biological activities. Following that, this study aims to compare the levels of various cytokines and to investigate the role of defensins between pregnant women with confirmed COVID-19 infection and pregnant women without any defined risk factor. TNF-α, TGF-β, IL-2 and IL-10, β-defensins, have been evaluated by gene expression in our population. At the same time, by ELISA assay IL-6, IL-8, defensin alpha 1, defensin beta 1 and defensin beta 4 have been measured. The data obtained show that mothers affected by COVID-19 have an increase in pro-inflammatory factors (TNF-α, TGF-β, IL-2, IL-6, IL-8) compared to controls;this increase could generate a sort of 'protection of the fetus';from virus attacks. Contemporarily, we have an increase in the anti-inflammatory cytokine IL-10 and an increase in AMPs, which highlights how the mother's body is responding to the viral attack. These results allow us to hypothesize a mechanism of 'trafficking';of antimicrobial peptides from the mother to the fetus that would help the fetus to protect itself from the infection in progress.

4.
Genes (Basel) ; 12(6)2021 06 08.
Article in English | MEDLINE | ID: covidwho-1264428

ABSTRACT

To identify host genetic determinants involved in humoral immunity and associated with the risk of developing severe COVID-19, we analyzed 500 SARS-CoV-2 positive subjects from Southern Italy. We examined the coding sequences of 10 common variable immunodeficiency-associated genes obtained by the whole-exome sequencing of 121 hospitalized patients. These 10 genes showed significant enrichment in predicted pathogenic point mutations in severe patients compared with the non-severe ones. Moreover, in the TNFRSF13C gene, the minor allele of the p.His159Tyr variant, which is known to increase NF-kB activation and B-cell production, was significantly more frequent in the 38 severe cases compared to both the 83 non-severe patients and the 375 asymptomatic subjects further genotyped. This finding identified a potential genetic risk factor of severe COVID-19 that not only may serve to unravel the mechanisms underlying the disease severity but, also, may contribute to build the rationale for individualized management based on B-cell therapy.


Subject(s)
B-Cell Activation Factor Receptor/genetics , COVID-19/etiology , COVID-19/genetics , Female , Gene Frequency , Humans , Italy , Male , Middle Aged , Polymorphism, Single Nucleotide , Retrospective Studies , Severity of Illness Index
5.
Int J Mol Sci ; 22(10)2021 May 20.
Article in English | MEDLINE | ID: covidwho-1244036

ABSTRACT

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10-5) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.


Subject(s)
COVID-19/genetics , COVID-19/metabolism , Genetic Predisposition to Disease , Receptors, CCR5/genetics , Receptors, CCR5/metabolism , Alleles , Bronchi/metabolism , Bronchi/pathology , Bronchi/virology , COVID-19/physiopathology , Chromosomes, Human/genetics , Cohort Studies , Computational Biology , Databases, Genetic , Genome-Wide Association Study , Genotype , Humans , Lung/metabolism , Lung/pathology , Lung/virology , Polymorphism, Single Nucleotide , Whole Exome Sequencing
6.
iScience ; 24(4): 102322, 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1144743

ABSTRACT

The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex, and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five single nucleotide polymorphisms (SNPs) correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target.

7.
Int J Environ Res Public Health ; 18(4)2021 02 05.
Article in English | MEDLINE | ID: covidwho-1069810

ABSTRACT

Coronaviruses (CoVs) are a large family of respiratory viruses that can cause mild to moderate illness. The new variant COVID-19 has started to spread rapidly since December 2019, posing a new threat to global health. To counter the spread of the virus, the Italian government forced the population to close all activities starting from 9 March 2020 to 4 May 2020. In this scenario, we conducted a cross-sectional study on a heterogeneous sample (average age of 28 ± 12 years, 62.6% females) of the University of Naples Federico II (Italy). The aim of the study was to describe the lifestyle change in the university population during quarantine for the COVID 19 pandemic. Participants compiled an online survey consisting of 3 sections: socio-demographic data, dietary behaviours, physical activity habits and psychological aspects. The different results by gender are: 90.8% of females continued to work from home (81.9% were students); 34.8% increased their physical activity; and, only 0.8% prefer ready meals. Whereas, the same percentage of men continued to work from home (90%), but only 72.1% were students (p < 0.001 vs. females), only 23.9% increased physical activity (p < 0.001) and 1.7% favous ready meals. Our data shows that the male population was more affected by isolation and quarantine reporting more unfavourable behavioural changes.


Subject(s)
COVID-19 , Diet , Exercise , Faculty , Pandemics , Students , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Italy/epidemiology , Life Style , Male , Quarantine , Surveys and Questionnaires , Universities , Work , Young Adult
8.
Int J Environ Res Public Health ; 18(3)2021 01 21.
Article in English | MEDLINE | ID: covidwho-1067744

ABSTRACT

Coronaviruses (CoVs) represent a large family of RNA viruses that can infect different living species, posing a global threat to human health. CoVs can evade the immune response, replicate within the host, and cause a rapid immune compromise culminating in severe acute respiratory syndrome. In humans, the immune system functions are influenced by physical activity, nutrition, and the absence of respiratory or cardiovascular diseases. This review provides an in-depth study between the interactions of the immune system and coronaviruses in the host to defend against CoVs disease.


Subject(s)
COVID-19 , Cardiovascular Diseases , Diet , Exercise , Immune System , Respiratory Tract Diseases , COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Humans , Respiratory Tract Diseases/epidemiology
9.
Int J Environ Res Public Health ; 18(3)2021 01 21.
Article in English | MEDLINE | ID: covidwho-1045437

ABSTRACT

Coronaviruses (CoVs) represent a large family of RNA viruses that can infect different living species, posing a global threat to human health. CoVs can evade the immune response, replicate within the host, and cause a rapid immune compromise culminating in severe acute respiratory syndrome. In humans, the immune system functions are influenced by physical activity, nutrition, and the absence of respiratory or cardiovascular diseases. This review provides an in-depth study between the interactions of the immune system and coronaviruses in the host to defend against CoVs disease.


Subject(s)
COVID-19 , Cardiovascular Diseases , Diet , Exercise , Immune System , Respiratory Tract Diseases , COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Humans , Respiratory Tract Diseases/epidemiology
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