ABSTRACT
Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic [~]0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
ABSTRACT
Coronavirns disease 2019 is a pandemic viral disease affecting also obstetric patients and uncertainties exist about the prognostic role of inflammatory biomarkers and hemocytometry values in patients with this infection. To clarify that, we assessed the values of several inflammatory biomarkers and hemocytometry variables in a cohort of obstetric patients hospitalized with coronavirus disease 2019 and we correlated the values at admission with the need of oxygen supplementation during the hospitalization. Overall, among 27 (61%) pregnant women and 17 (39%) post-partum women, 6 (14%) patients received oxygen supplementation and 2 (4%) required admission to intensive care unit but none died. During hospitalization neutrophils (p=0.002), neutrophils to lymphocytes ratio (p=0.037) and C reactive protein (p<0.001) decreased significantly, whereas lymphocytes (p<0.001) and platelets (p<0.001) increased. Leukocytes and lymphocytes values at admission were correlated with oxygen need, with respectively a 1% and 5% higher risk of oxygen supplementation for each 1,000 cells decrease. Overall, in obstetric patients hospitalized with coronavirus disease 2019, C reactive protein is the inflammatory biomarker that better mirrors the course of the disease whereas D-dimer or ferritin are not reliable predictors of poor outcome. Care to the need of oxygen supplementation should be reserved to patients with reduced leukocytes or lymphocytes values at admission.
ABSTRACT
BackgroundRespiratory failure is a key feature of severe Covid-19 and a critical driver of mortality, but for reasons poorly defined affects less than 10% of SARS-CoV-2 infected patients. MethodsWe included 1,980 patients with Covid-19 respiratory failure at seven centers in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe (Milan, Monza, Madrid, San Sebastian and Barcelona) for a genome-wide association analysis. After quality control and exclusion of population outliers, 835 patients and 1,255 population-derived controls from Italy, and 775 patients and 950 controls from Spain were included in the final analysis. In total we analyzed 8,582,968 single-nucleotide polymorphisms (SNPs) and conducted a meta-analysis of both case-control panels. ResultsWe detected cross-replicating associations with rs11385942 at chromosome 3p21.31 and rs657152 at 9q34, which were genome-wide significant (P<5x10-8) in the meta-analysis of both study panels, odds ratio [OR], 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.14x10-10 and OR 1.32 (95% CI, 1.20 to 1.47; P=4.95x10-8), respectively. Among six genes at 3p21.31, SLC6A20 encodes a known interaction partner with angiotensin converting enzyme 2 (ACE2). The association signal at 9q34 was located at the ABO blood group locus and a blood-group-specific analysis showed higher risk for A-positive individuals (OR=1.45, 95% CI, 1.20 to 1.75, P=1.48x10-4) and a protective effect for blood group O (OR=0.65, 95% CI, 0.53 to 0.79, P=1.06x10-5). ConclusionsWe herein report the first robust genetic susceptibility loci for the development of respiratory failure in Covid-19. Identified variants may help guide targeted exploration of severe Covid-19 pathophysiology.
ABSTRACT
BackgroundThe management of healthcare workers (HCWs) exposed to confirmed cases of COVID-19 is still a matter of debate. It is unclear whether these subjects should be tested in the absence of symptoms and if those can guide diagnosis. MethodsOccupational and clinical characteristics of all the consecutive HCWs who performed a nasopharyngeal swab for the detection of SARS-CoV-2 in a University Hospital from February 24, 2020, to March 31, 2020, were collected. Frequencies of positive tests were compared according to selected variables. Multivariable logistic regression analyses were then applied. FindingsPositive tests were 138 among 1,573 HCWs (8.8%, 95% confidence interval [CI]: 7.4-10.3), with a marked difference between symptomatic (20.2%, 95% CI: 16.7-24.1) and asymptomatic (3.7%, 95% CI: 2.7-5.1) subjects (p<0.001). Physicians were the group with the highest frequency of positive tests (10.6%, 95% CI: 8.3-13.4) whereas clerical workers and technicians displayed the lowest frequency (2.9%, 95% CI: 0.8-7.3). The likelihood of being positive increased with the number of reported symptoms and the strongest predictors of a positive test were taste and smell alterations (odds ratio [OR] = 29.7) and fever (OR = 7.21). The median time from first positive test to a negative test was 23 days (95% CI: 19-24). InterpretationIn this Italian group of HCWs exposed to confirmed cases of COVID-19 the presence of symptoms, especially taste and smell alterations and fever, was associated with SARS-CoV-2 infection. The median time to clear the virus from nasopharynx was 23 days. Fundingnone related to the content of this manuscript. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles published in English up to April 25, 2020, using the keywords "SARS-CoV-2", "COVID-19", "2019-nCoV", AND "healthcare workers","HCW", AND "testing", "nasopharyngeal swab". We found one article: Roll-out of SARS-CoV-2 testing for healthcare workers at a large NHS Foundation Trust in the United Kingdom, March 2020 published in Euro Surveillance. Reviewing the pre-print website medRxiv with the same keywords we identified two additional studies: SARS-CoV-2 infection in Health Care Workers in a large public hospital in Madrid, Spain, during March 2020, and SARS-CoV-2 infection in 86 healthcare workers in two Dutch hospitals in March. Added value of this studyWe showed that, even if symptomatic healthcare workers had a much higher probability of positive test, almost one third of those infected were asymptomatic. Specific symptoms, namely taste and smell alterations and fever, were strongly associated with the infection. Finally, the median time to clear the virus from nasopharynx was 23 days. Implications of all the available evidenceScreening strategies for healthcare workers exposed to COVID-19 patients should take in account the significant proportion of asymptomatic carriers and the predictive role of specific symptoms. Moreover, healthcare workers coming back to work after a positive test should be aware of the long-time of viral shedding from nasopharynx.
ABSTRACT
BackgroundSevere acute respiratory syndrome coronavirus 2 is a recently discovered pathogen responsible of coronavirus disease 2019 (COVID-19). The immunological changes associated with this infection are largely unknown. MethodsWe evaluated the peripheral blood mononuclear cells profile of 63 patients with COVID-19 at diagnosis and the presence of association with inflammatory biomarkers and 28-days mortality. ResultsLymphocytopenia was present in 51 of 63 (80.9%) patients. This reduction was mirrored also on CD8+ lymphocytes (128 cells/L), natural killer cells (67 cells/L) and natural killer T cells (31 cells/L). Monocytes were preserved in total number but displayed a subpopulation composed mainly of cells with a reduced expression of both CD14 and HLA-DR. A direct correlation was found between serum values of IL-6 and the frequency of Th2 lymphocytes (R=0.17; p=0.04) but not with the monocytes count (R=0.01; p=0.60). Patients who died in the 28 days from admission (N=10, 15.9%), when compared to those who did not, displayed lower mean values of CD3+ (p=0.028) and CD4+ cells (p=0.042) and higher mean percentages of CD8+/CD38+/HLA-DR+ lymphocytes (p=0.026). ConclusionsThe early phases of COVID-19 are characterized by lymphocytopenia, predominance of Th2 lymphocytes and less immunocompetent monocytes, which include atypical mononuclear cells. eTOC-At diagnosis patients with COVID-19 have lymphocytopenia -Monocytes with both normal or altered scatter properties display a reduced expression of CD14 and HLA-DR in most of COVID-19 patients -Patients who die in the 28 days from admission have lower values of CD3+ and CD4+ cells and higher percentages of activated CTL cells compared to those who survive
