Sex differences in immunological responses to COVID-19: a cross-sectional analysis of a single-centre cohort.
Ontology highlight
ABSTRACT:
SUBMITTER: Arulkumaran N
PROVIDER: S-EPMC8156911 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundMales and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration.MethodsWe performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence.ResultsWe found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively, P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively, P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio [HR] = 2.22, 95% confidence interval [CI]: 1.3-3.6, P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 [6.5%] vs. 63/1499 [4.2%], in males and females, respectively, P = 0.002) and hepatic abnormality (650/1588 [40.9%] vs. 475/1499 [31.7%], P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients.ConclusionsMales had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.
| S-EPMC8256650 | biostudies-literature
Project description:BackgroundAn important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications. Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy. To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.MethodsIn this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital. Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range. We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes. We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable. We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality. Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.Findings68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls. Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014). VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients. We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients. In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087).InterpretationOur findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death. Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.FundingThis work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health.
| S-EPMC7326446 | biostudies-literature
Project description:BackgroundA high prevalence of antiphospholipid antibodies has been reported in case series of patients with neurological manifestations and COVID-19; however, the pathogenicity of antiphospholipid antibodies in COVID-19 neurology remains unclear.MethodsThis single-centre cross-sectional study included 106 adult patients: 30 hospitalised COVID-neurological cases, 47 non-neurological COVID-hospitalised controls, and 29 COVID-non-hospitalised controls, recruited between March and July 2020. We evaluated nine antiphospholipid antibodies: anticardiolipin antibodies [aCL] IgA, IgM, IgG; anti-beta-2 glycoprotein-1 [aβ2GPI] IgA, IgM, IgG; anti-phosphatidylserine/prothrombin [aPS/PT] IgM, IgG; and anti-domain I β2GPI (aD1β2GPI) IgG.FindingsThere was a high prevalence of antiphospholipid antibodies in the COVID-neurological (73.3%) and non-neurological COVID-hospitalised controls (76.6%) in contrast to the COVID-non-hospitalised controls (48.2%). aPS/PT IgG titres were significantly higher in the COVID-neurological group compared to both control groups (p < 0.001). Moderate-high titre of aPS/PT IgG was found in 2 out of 3 (67%) patients with acute disseminated encephalomyelitis [ADEM]. aPS/PT IgG titres negatively correlated with oxygen requirement (FiO2 R=-0.15 p = 0.040) and was associated with venous thromboembolism (p = 0.043). In contrast, aCL IgA (p < 0.001) and IgG (p < 0.001) was associated with non-neurological COVID-hospitalised controls compared to the other groups and correlated positively with d-dimer and creatinine but negatively with FiO2.InterpretationOur findings show that aPS/PT IgG is associated with COVID-19-associated ADEM. In contrast, aCL IgA and IgG are seen much more frequently in non-neurological hospitalised patients with COVID-19. Characterisation of antiphospholipid antibody persistence and potential longitudinal clinical impact are required to guide appropriate management.FundingThis work is supported by UCL Queen Square Biomedical Research Centre (BRC) and Moorfields BRC grants (#560441 and #557595). LB is supported by a Wellcome Trust Fellowship (222102/Z/20/Z). RWP is supported by an Alzheimer's Association Clinician Scientist Fellowship (AACSF-20-685780) and the UK Dementia Research Institute. KB is supported by the Swedish Research Council (#2017-00915) and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and theUK Dementia Research Institute at UCL. BDM is supported by grants from the MRC/UKRI (MR/V007181/1), MRC (MR/T028750/1) and Wellcome (ISSF201902/3). MSZ, MH and RS are supported by the UCL/UCLH NIHR Biomedical Research Centre and MSZ is supported by Queen Square National Brain Appeal.
| S-EPMC8358233 | biostudies-literature
Project description:ObjectiveThis study compared demographic, clinical and laboratory characteristics between patients with radiographic and non-radiographic axial spondyloarthritis (axSpA).MethodsIn this single-centre cross-sectional study, a total of 246 patients with axSpA fulfilling the imaging arm of Assessment of SpondyloArthritis International Society classification criteria were recruited. A total of 140 patients were diagnosed as non-radiographic axial spondyloarthritis (nr-axSpA), and 106 patients had ankylosing spondylitis (AS). Sociodemographic characteristics, disease manifestations, clinical and laboratory disease activity and their differences between subsets were analysed. P values below 0.05 with CI 95% were considered statistically significant.ResultsMore nr-axSpA patients were women (61.4%) compared with 24.7% of AS patients. First symptoms developed earlier in AS patients compared with nr-axSpA (23.0 (IQR 17.5-30.0) vs 27.8 (IQR 21.0-33.7) years, p=0.001). Disease manifestations did not differ, but patients with nr-axSpA experienced peripheral arthritis more frequently (35.7% vs 17.0%, p=0.001) with less hip involvement (8.6% vs 18.9%, p=0.022) compared with patients with AS. Patients with AS exhibited worse spinal mobility and physical function compared with nr-axSpA. AS Disease Activity Scores and CRP levels were significantly higher in patients with AS compared with nr-axSpA (2.4 (IQR 1.7-2.8) vs 2.0 (IQR 1.1-2.3), p=0.022?and 7.1 (IQR 2.6-14.9) vs 2.5 (IQR 0.8-8.2)?mg/L, p<0.001, respectively).ConclusionsOur data demonstrated some known and also novel differences between the two imaging arm fulfilling axSpA subgroups. Non-radiographic patients were mostly women who had experienced shorter disease duration, milder disease activity and better functional status with less hip involvement but more peripheral arthritis compared with patients with AS.
| S-EPMC6500279 | biostudies-literature
Project description:The global increase in Diabetes Mellitus (DM) has led to an increase in DM-Chronic Kidney Disease (DM-CKD). In this cross-sectional observational study we aimed to define phenotypes for patients with DM-CKD that in future may be used to individualise treatment We report 4 DM-CKD phenotypes in 220 patients recruited from Imperial College NHS Trust clinics from 2004-2012. A robust principal component analysis (PCA) was used to statistically determine clusters with phenotypically different patients. 163 patients with complete data sets were analysed: 77 with CKD and 86 with DM-CKD. Four different clusters were identified. Phenotypes 1 and 2 are entirely composed of patients with DM-CKD and phenotypes 3 and 4 are predominantly CKD (non-DM-CKD). Phenotype 1 depicts a cardiovascular phenotype; phenotype 2: microvascular complications with advanced DM-CKD; phenotype 3: advanced CKD with less anaemia, lower weight and HbA1c; phenotype 4: hypercholesteraemic, younger, less severe CKD. We are the first group to describe different phenotypes in DM-CKD using a PCA approach. Identification of phenotypic groups illustrates the differences and similarities that occur under the umbrella term of DM-CKD providing an opportunity to study phenotypes within these groups thereby facilitating development of precision/personalised targeted medicine.
| S-EPMC5758706 | biostudies-literature
Project description:ObjectiveTo explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions.DesignCross-sectional study.SettingEast London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) Study at Barts Health National Health Service Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020.ParticipantsEL-PaC-Epidem Study participants, alive on 12 February 2020, and living in East London within the previous 6 months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background.Main outcome measureCOVID-19 incidence and mortality.ResultsSome 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance misusers were at more risk of infection, so were patients on vitamin D treatment. The higher ORs in patients with chronic pancreatic or mild liver conditions, age >70, and a history of smoking or obesity were due to coexisting comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19).ConclusionsIn this large population-based study of patients with HPB conditions, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multimorbidities, substance misuse and a history of vitamin D treatment independently posed higher odds of acquiring COVID-19 compared with their respective counterparts. The odds of death were significantly high for men and Black people.
| S-EPMC8057071 | biostudies-literature
Project description:AimTo examine the effect of sex on migraine trigger factors.MethodsPrevalence of 11 frequently reported trigger factors was determined in a cross-sectional study among migraine patients from a validated migraine database (n = 5725 females and n = 1061 males). Female-to-male odds ratios were calculated for each trigger, using a logistic regression model with attack frequency and migraine subtype (with or without aura) as covariates. Additionally, the effect of sex on total number of triggers per individual was determined.ResultsThe top three most reported triggers in women were menstruation (78%), stress (77%), and bright light (69%). Men reported stress (69%), bright light (63%), and sleep deprivation (60%) most frequently as provoking factors. The following triggers were more often reported by women than men: Bright light (odds ratio 1.29 [95% CI 1.12-1.48]; p = 0.003), stress (1.47 [1.27-1.69]; p < 0.001), skipping a meal (1.24 [1.09-1.42]; p = 0.015), sleep deprivation (1.37 [1.20-1.57]; p < 0.001), high altitudes (1.70 [1.40-2.09]; p < 0.001), and weather changes (1.35 [1.18-1.55]; p < 0.001). Women reported more triggers than men, even when menstruation was disregarded (mean ± SD: 4.6 ± 2.3 and 4.3 ± 2.3; p < 0.001).Conclusion: Women report migraine trigger factors to be provocative of their attacks more frequently than men, which may be related to a lower migraine threshold due to sex hormonal changes.
| S-EPMC8111230 | biostudies-literature
Project description:There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than among women1-5. However, whether immune responses against severe acute respiratory syndrome coronavirus (SARS-CoV-2) differ between sexes, and whether such differences correlate with the sex difference in the disease course of COVID-19, is currently unknown. Here we examined sex differences in viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. Male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. By contrast, female patients had more robust T cell activation than male patients during SARS-CoV-2 infection. Notably, we found that a poor T cell response negatively correlated with patients' age and was associated with worse disease outcome in male patients, but not in female patients. By contrast, higher levels of innate immune cytokines were associated with worse disease progression in female patients, but not in male patients. These findings provide a possible explanation for the observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of male and female patients with COVID-19.
| S-EPMC7725931 | biostudies-literature
Project description:PURPOSE:Homeless persons have a high risk for tuberculosis. The prevalence of latent tuberculosis infection and the risk for a progression to active tuberculosis is higher in the homeless than in the general population. The objective was to assess the prevalence and risk factors of tuberculosis/latent tuberculosis infection in a homeless population in Germany. METHODS:Homeless individuals (n = 150) were enrolled in a cross-sectional study at three shelters in Münster, Germany (October 2017-July 2018). All participants were screened using an ELISPOT interferon-? release assay (IGRA). Those participants tested positive/borderline by IGRA provided three sputa for microbiological analysis (line probe assay, microscopy, culture) and underwent a chest X-ray to screen for active pulmonary TB. Risk factors for tuberculosis/latent tuberculosis infection were analysed using a standardized questionnaire. RESULTS:Of the 142 evaluable IGRA, 21 (15%) were positive and two (1%) were borderline. No participant with a positive/borderline IGRA had an active tuberculosis as assessed by chest X-ray and microbiology. A negative IGRA was associated with a citizenship of a low-incidence country for tuberculosis (according to WHO, p = 0.01), low-incidence country of birth (p<0.001) or main residence in a low-incidence country in the past five years (p = 0.002). CONCLUSIONS:The prevalence of latent tuberculosis infection (diagnosed by a positive/borderline IGRA) was 16%; no active tuberculosis was detected. The highest risk for latent tuberculosis infection was found in patients from high-incidence countries. This population at risk should be either treated for latent tuberculosis infection or need to be monitored to early detect a progression into active disease.
| S-EPMC6435138 | biostudies-literature
Project description:BackgroundThe COVID-19 (SARS-CoV-2) pandemic has increased infection control vigilance across several modes of patient contact. However, it is unknown whether hygiene pertaining to stethoscopes, which carry the potential for pathogenic contamination, has also shifted accordingly.AimTo characterize pandemic-related changes in stethoscope hygiene.MethodsWe surveyed healthcare providers at three major medical centres. Questions quantitatively (Likert scale and frequency) assessed stethoscope hygiene beliefs and practices with two components: before and during COVID-19. Participants were grouped based on performance of optimal stethoscope hygiene (after every patient) before and during COVID-19. Groups were compared using χ2 and analysis of variance (ANOVA).FindingsOf the 515 (10%) who completed the survey, 55 were excluded (N = 460). Optimal hygiene increased from 27.4% to 55.0% (P < 0.001). There were significant increases in Likert scores for all questions pertaining to knowledge of stethoscope contamination (P < 0.001). Belief in stethoscope contamination increased (P < 0.001) despite no change in perceived hygiene education. Resident physicians were less likely compared with attending physicians and nurses to have adopted optimal hygiene during COVID-19 (P < 0.001).ConclusionDespite a positive shift in stethoscope hygiene during COVID-19, optimal hygiene was still only performed by around half of providers. Educational interventions, particularly targeting early-career providers, are encouraged.
| S-EPMC9167726 | biostudies-literature