During the early stages of the COVID-19 pandemic, significant differences in mortality patterns emerged based on sex and geographical regions. While we were studying on the heredity of variants of the Y chromosome, we observed that regional variations in mortality rates appeared to correlate with the geographical distribution of certain variants of the Y chromosome. This observation led us to propose that some genes on the Y chromosome, with an influence on immune responses, may represent a confounding factor in the observed geographical mortality differences.

In this analysis, we investigate the potential associations between COVID-19 morbidity and disease-specific mortality and specific Y chromosome variants. The study is based on publicly available pandemic data validated by state authorities or presented in scientific literature documented in PubMed and Medline.

We find that Y chromosome haplogroups in different populations exhibit wave-like patterns corresponding with persistent global disparities in COVID-19-related mortality.

These findings warrant further research to uncover possible new pathophysiological mechanisms.

Objectives. To determine the overall mortality and risk factors of COVID-19 patients who were admitted to the Home Isolation (HI) program in Bangkok, Thailand, during the epidemic crisis in 2021. Methods. We conducted a retrospective cohort study using the data from a government telehealth application from July to December 2021. The vital status was verified from the government database on September 20, 2022. We used survival analysis to analyze the 28-day mortality and independently associated factors. Results. Of 90 854 reported cases, the average age was 37.27 years, and half were men. Initial symptoms included being asymptomatic (51.66%), having mild symptoms (35.60%), or experiencing severe symptoms requiring nonurgent (11.27%) or urgent referral (1.47%). The 28-day mortality rate was 0.80%. Factors associated with 28-day mortality included older age, male gender, higher body mass index, severity of initial symptoms, and time to admission. Conclusions. The Home Isolation program was able to manage a high volume of patients, including severe cases, exceeding its initial design. Thailand's COVID-19 mortality rate remained relatively low compared with other countries. Proactive bed surge planning and continuous plan improvement were crucial for future preparedness. (Am J Public Health. 2025;115(4):605-616. https://doi.org/10.2105/AJPH.2024.307922).

The inflammatory response associated with COVID-19 varies with sex, potentially affecting disease outcomes. Males have a higher risk of complications compared to females, requiring an evaluation of differences in inflammatory response severity based on sex.

To compare clinical data, biochemical biomarkers, and outcomes among hospitalized COVID-19 patients in Latin America and the Caribbean (LA&C) based on sex and to perform a cluster analysis of biomarker profiles for both sexes.

This prospective, multicenter observational registry made by the Inter-American Council of Heart Failure and Pulmonary Hypertension of the Inter-American Society of Cardiology included hospitalized COVID-19 patients from 44 hospitals in 14 countries in LA&C between May 1, 2020, and June 30, 2021.

Of 3,260 patients (1,201 females and 2,059 males), males had higher C-reactive protein and ferritin levels, while females had higher natriuretic peptides and d-dimer levels. Males had more cardiovascular complications (acute coronary syndrome [3.3% vs. 2.2%], decompensated heart failure [8.9% vs. 7.8%], pulmonary embolism [4.4% vs. 2.9%]), intensive care unit (ICU) admissions (56.9% vs. 47.7%), and overall mortality (27.5% vs. 22.1%). Cluster analysis identified three groups: one with normal-range biomarkers but elevated ferritin, one with coagulation abnormalities, and one with an inflammatory profile linked to renal injury and increased non-cardiovascular mortality.

In the LA&C population hospitalized with COVID-19, males had higher inflammatory biomarker levels, correlating with increased cardiovascular complications and mortality. The cluster with an inflammatory profile showed higher non-cardiovascular mortality, while clusters with elevated ferritin levels were associated with increased ICU admissions.

The COVID-19 pandemic has severely tested global health systems. Non-invasive respiratory support, especially combining high-flow nasal cannula (HFNC) and continuous positive airway pressure, has effectively treated COVID-19 induced Acute Hypoxemic Respiratory Failure and reduced mortality. However, HFNC alone is more comfortable, better tolerated, and less costly than non-invasive ventilation. Understanding which patients benefit from HFNC monotherapy versus combined therapies is essential.

This observational study included patients admitted to the intermediate respiratory care unit of a COVID-19 hospital between December 2020 and September 2021. All patients treated with HFNC were included (n = 1301). HFNC failure was defined as the need for escalated therapy (non-invasive ventilation, intubation) or death. Epidemiological, clinical, non-invasive respiratory support parameters, and laboratory data were collected, and a multivariable analysis identified key determinants.

HFNC was successful in 39.9 % of patients. (n = 511) Risk factors for HFNC failure included increased age, male gender, obesity, obstructive sleep apnea, higher respiratory rate, initial SpO2/FiO2 ≤ 148, and initial PaO2/FiO2 ≤ 100. An increase in the ROX Index at 24 h and slower disease progression were associated with successful treatment. These findings led to the developmet of an index to identify patients who benefit most from HFNC monotherapy.

HFNC monotherapy can be effective for a specific profile of patients with Acute Hypoxemic Respiratory Failure due to COVID-19. This tool may help manage these patients more appropriately. Further studies are needed to determine if these findings can be applied to Acute Hypoxemic Respiratory Failure caused by other pathologies.

This study underscores the importance of early identification and management of patients at risk of HFNC failure in intermediate respiratory care units. By recognizing factors such as age, comorbidities, and respiratory indices, healthcare providers can implement targeted strategies to enhance HFNC success. These strategies may include more stringent monitoring, tailored respiratory support, and timely escalation to more intensive therapies if needed. Our findings highlight the need for a comprehensive approach to managing severe respiratory failure in critical care settings, ultimately improving patient outcomes and reducing the burden on healthcare systems.

SARS-CoV-2 responsible for the COVID-19 pandemic, infiltrates the human body by binding to the ACE2 receptor in the respiratory system cell membranes, leading to severe lung tissue damage. An analog of ACE2, ACE1, has gained attention due to its well-known Deletion/Insertion (D/I) polymorphism, which seems to be associated with COVID-19 outcomes. This study aims to reveal the allelic and genotypic frequencies of the rs4646994 polymorphism in the Moroccan population and investigate the association between COVID-19 outcomes and both genotypic and demographic data.

We screened 162 Moroccan COVID-19 patients for the ACE1 gene D/I polymorphism using PCR amplification of the ACE1 polymorphic region within intron 16. Statistical analysis of the relationship between COVID-19 outcomes and each of the genetic and demographic data was performed using R software. The D allele was present in 74% of subjects. Homozygous (II) and heterozygous (DI) genotypes for the Insertion allele were present in 41.4% and 5.6% of patients, respectively. The median age in the COVID-19 'critical symptoms' category was significantly higher and gradually decreased with less severe symptoms. Similarly, males were significantly overrepresented in the 'critical symptoms' category, while females predominated in the 'mild symptoms' category.

The present study reports the prevalence of ACE1 D/I alleles for the first time in the Moroccan population and confirms the strong association of severe COVID-19 outcomes with male sex and older age. Moreover, this work is the first to explore the relationship between ACE1 D/I polymorphism and COVID-19 clinical outcomes in North African adults. The lack of a significant association may be due to cohort size or population-specific factors. A comprehensive investigation in a larger North African cohort is highly recommended.

Identifying effective treatments and policies early in a pandemic is challenging because only limited and noisy data are available and biological processes are unknown or uncertain. Consequently, classical statistical procedures may not work or require strong structural assumptions. We present an information-theoretic approach that can overcome these problems and identify effective treatments and policies. The efficacy of this approach is illustrated using a study conducted at the beginning of the COVID-19 pandemic. We applied this approach with and without prior information to the limited international data available in the second month (24 April 2020) of the COVID-19 pandemic. To check if our results were plausible, we conducted a second statistical analysis using an international sample with millions of observations available at the end of the pandemic's pre-vaccination period (mid-December 2020). Even with limited data, the information-theoretic estimates from the original study performed well in identifying influential factors and helped explain why death rates varied across nations. Later experiments and statistical analyses based on more recent, richer data confirm that these factors contribute to survival. Overall, the proposed information-theoretic statistical technique is a robust method that can overcome the challenges of under-identified estimation problems in the early stages of medical emergencies. It can easily incorporate prior information from theory, logic, or previously observed emergencies.

Postacute infection syndromes like Long Covid disproportionately affect females, differing in prevalence, symptoms, and potential causes from males. This Viewpoint highlights these sex differences, gaps in current understanding, and the critical need for sex-based research.

Background: Increased mortality and occurrence of cardiovascular (CV) outcomes during hospitalization and in short-term follow-up for moderate to severe SARS-CoV-2 infection have been associated with male sex, yet data regarding long-term outcomes by sex and COVID-19 variant (Alpha, Delta, and Omicron) are limited. Methods: This prospective study of 4882 patients examines potential differences by sex in the occurrence of primary combined cardiovascular outcomes (CV death, CV hospitalization, myocardial infarction (MI), stroke, pulmonary embolism) as well as secondary outcomes (CV death, cardiovascular hospitalizations, myocardial infarction, stroke, pulmonary embolism) at 18-month follow-up after urgent hospitalization for SARS-CoV-2-associated pneumonia, as well as evaluating for differences during the three COVID-19 waves. Survival rate was analyzed for the entire cohort by sex and SARS-CoV-2 variant and adjusted for age using the multiple Kaplan-Meier method. To compare survival in groups of men and women for each wave, the Gehan-Wilcoxon test was applied with significance p < 0.05. Univariate Cox proportional hazards models were used to search for potential risk factors of CV death at 18-months follow-up separately for men and women in each COVID-19 wave. Results: Men had significantly higher 18-month CV mortality compared to women in the Delta wave (6.13% men vs. 3.62% women, p = 0.017). Although men had higher percentages of all other CV endpoints (excepting pulmonary embolism) at follow-up during the Delta wave, none were significant compared with women, except for the combined CV endpoint (16.87% men vs. 12.61% women, p = 0.017). No significant differences by sex in CV outcomes were seen during the Alpha and Omicron variants. Discrepancies in CV outcomes in demographical data and concomitant disease between the COVID-19 variants of concern existed. Conclusions: Higher male mortality and higher but non-significant incidences of CV outcomes occurred during the Delta wave of the COVID-19 pandemic, with the lowest incidence of CV outcomes observed during the Omicron variant.

Sex differences in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) susceptibility, illness severity, and hospital course are widely acknowledged. The effects of sex on outcomes experienced by patients with severe Coronavirus Disease 2019 (COVID-19) admitted to the intensive care unit (ICU) remains unknown.

To determine the effects of sex on ICU mortality in patients with COVID-19 METHODS: This retrospective analysis of an international multi-center prospective observational database included adults admitted to ICU for treatment of acute COVID-19 between 1st January 2020 and 30th June 2022. The primary outcome was ICU mortality. Multivariable Cox regression was used to ascertain the hazard of death (Hazard Ratio=HR) adjusted for pre-selected covariates. The secondary outcome was sex differences in complications of COVID-19 during hospital stay.

Overall, 10,259 patients (3,314 females, 6,945 males) were included with a median age of 60 (interquartile range [IQR]=49-68) and 59 (IQR=49-67) years, respectively. Baseline characteristics were similar between sexes. More females were non-smokers (65% vs. 44 %, p < 0.01) and obese (39% vs. 30 %, p < 0.01), compared to males. Also, males received greater ICU intervention (mechanical ventilation, prone ventilation, vasopressors, and tracheostomy) than females. Males had a greater hazard of death (compared to females, HR=1.14; 95 % CI=1.02-1.26). Adjustment for complications during hospital stay did not alter the hazard of death (HR=1.16; 95 % CI=1.05-1.28). Males had a significantly elevated hazard of death among patients who received ECMO (HR=1.24; 95 % CI=1.01-1.53). Male sex was associated with cardiac arrest (adjusted OR [aOR]=1.37; 95 % CI=1.16-1.62) and PE (aOR=1.28; 95 % CI=1.06-1.55).

Among patients admitted to ICU for severe COVID-19, males experienced higher severity of illness and more frequent intervention than females. Ultimately, the hazard of death was moderately elevated in males compared to females despite greater PE and cardiac arrest.

The emergence of the SARS-CoV-2 Omicron variant has posed a significant global public health challenge. Elucidating the laboratory profiles of individuals infected with this variant is crucial for assessing organ damage. This study aimed to investigate the variations in liver function tests and their correlation with demographic characteristics and inflammatory markers in patients with early Omicron variant infections.

A retrospective cohort study was conducted on 1133 mild or asymptomatic COVID-19 cases at Tianjin First Central Hospital. Data on age, gender, body mass index (BMI), and serum markers were collected and analyzed. Statistical analyses were performed using SPSS software, version 24.0.

Abnormal liver function parameters, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TBIL), were observed in 314 (27.71%) patients. "Hepatocellular type" was identified in 56 (4.94%) patients, "cholestatic type" in 185 (16.33%) patients, and "mixed type" in 73 (6.44%) patients. In the mixed group, we observed a pronounced elevation in the levels of ALT, AST, and GGT. Moreover, the hepatocellular group exhibited a statistically significant increase in AST and ALT concentrations relative to both the normal and cholestatic groups. Notably, the cholestatic group demonstrated a substantial increment in ALP levels. Males had a significantly higher prevalence of "abnormal liver enzyme markers" compared to females. Patients with "abnormal liver enzyme markers" exhibited significantly decreased immunoglobulin G (IgG) levels and elevated levels of inflammatory markers, including procalcitonin (PCT), interleukin-6 (IL6), as well as C-reactive protein (CRP) compared to normal group. Logistic regression analysis revealed that male gender and PCT levels were significantly associated with the risk of abnormal liver enzyme markers. Patients in hepatocellular group were likely accompanied with high CRP levels, whereas those in the cholestatic type were associated with high IL6 levels.

Early Omicron infection might cause liver stress response. Elevated liver enzyme marker levels were correlated with age, gender, inflammatory factors, and IgG.

Since the discovery of COVID-19 in December 2019, the novel virus has spread globally causing significant medical and socio-economic burden. Although the pandemic has been curtailed, the virus and its attendant complication live on. A major global concern is its adverse impact on male fertility.

This study was aimed to give an up to date and robust data regarding the effect of COVID-19 on semen variables and male reproductive hormones.

Literature search was performed according to the recommendations of PRISMA. Out of the 852 studies collected, only 40 were eligible for inclusion in assessing the effect SARS-CoV-2 exerts on semen quality and androgens. More so, a SWOT analysis was conducted.

The present study demonstrated that SARS-CoV-2 significantly reduced ejaculate volume, sperm count, concentration, viability, normal morphology, and total and progressive motility. Furthermore, SARS-CoV-2 led to a reduction in circulating testosterone level, but a rise in oestrogen, prolactin, and luteinizing hormone levels. These findings were associated with a decline in testosterone/luteinizing hormone ratio.

The current study provides compelling evidence that SARS-CoV-2 may lower male fertility by reducing semen quality through a hormone-dependent mechanism; reduction in testosterone level and increase in oestrogen and prolactin levels.

Since the beginning of the COVID-19 pandemic, it has been evident that women and young people were less susceptible to severe infections compared to males. In a previous study, we observed a reduced prevalence of SARS-CoV-2 infections in hormonal-driven breast cancer patients undergoing SERM (selective estrogen receptor modulator) therapy with respect to other treatments inhibiting estrogen synthesis. In addition to being used in anticancer therapy, SERMs are also prescribed for postmenopausal osteoporosis prevention and treatment. Therefore, in this study, a retrospective analysis of the clinical outcomes of SARS-CoV-2 infections in a population of women over 50 years who were treated for the management of menopausal symptoms was performed. SARS-CoV-2 infections, hospitalizations, and death rates were evaluated in women residing in the Italian north-eastern Veneto Region who were undergoing treatment with Estrogen Modulators (EMs); Estrogen or Progestin, and their combination (EPs); Bisphosphonates (BIs); or cholecalciferol (vitamin D3) ± calcium supplementation (CC). The final cohort study included 124,393 women, of whom 6412 were found to be SARS-CoV-2 infected (CoV2+ve). The results indicated that only women treated with vitamin D3 alone or in combination with calcium showed a significant reduction in their SARS-CoV-2 infection risk by 26% (OR 0.74; 95%CI 0.60-0.91). On the other hand, an increased risk of hospitalization (OR 2.69; 95%CI 1.77-4.07) was shown for the same treatments. The results highlighted in this work contribute to shedding some light on the widely debated role of vitamin D in the prevention of SARS-CoV-2 infections and the disease's treatment.

There is limited long-term evidence on the effects of COVID-19 on vascular injury between male and female sex. An adult cohort of COVID-19 survivors (COVID+) and confirmed SARS-CoV-2 antibody-negative participants (COVID-) were prospectively enrolled. COVID+ participants who have documented the presence of persistent symptoms four weeks following infection were considered to have post-acute sequelae of COVID-19 (PASC). Non-invasive, FDA-approved EndoPAT (Endo-PAT2000) was used for endothelial assessment. COVID-(n = 94) were 1:1 propensity score matched to COVID+ (n = 151) on baseline covariates including sex. Among COVID+, 66.2% (n = 100) had PASC. Higher levels of coagulation marker, D-dimer (p = 0.001), and gut permeability marker, zonulin (p = 0.001), were associated with female sex. Estimated differences in augmentation index (AI) between COVID- (0.9 ± 17.2) and COVID+ (8.4 ± 15.7; p = 0.001) and between female and male sex (12.9 ± 1.9; p < .0001) were observed. Among COVID+ with PASC, the average AI (10.5 ± 1.6) was 9.7 units higher than COVID- (p < .0001) and 6.2 units higher compared to COVID+ with no PASC (p = 0.03). COVID+ PASC+ female sex had the highest AI (14.3 ± 1.9). The effects of SARS-CoV-2 infection on vascular function varies across strata of sex and female sex in the post-acute phase of COVID-19 have the worse arterial elasticity (highest AI).

An increasing number of studies have highlighted the existence of a sex-specific immune response, wherein men experience a worse prognosis in cases of acute inflammatory diseases. Initially, this sex-dependent inflammatory response was attributed to the influence of sex hormones. However, a growing body of evidence has shifted the focus toward the influence of chromosomes rather than sex hormones in shaping these inflammatory sex disparities. Notably, certain pattern recognition receptors, such as Toll-like receptors (TLRs), and their associated immune pathways have been implicated in driving the sex-specific immune response. These receptors are encoded by genes located on the X chromosome. TLRs are pivotal components of the innate immune system, playing crucial roles in responding to infectious diseases, including bacterial and viral pathogens, as well as trauma-related conditions. Importantly, the TLR-mediated inflammatory responses, as indicated by the production of specific proteins and cytokines, exhibit discernible sex-dependent patterns. In this review, we delve into the subject of sex bias in TLR activation and explore its clinical implications relatively to both the X chromosome and the hormonal environment. The overarching objective is to enhance our understanding of the fundamental mechanisms underlying these sex differences.

The aim of the study was to describe the facilitators, barriers to and level of uptake of COVID-19 vaccines among healthcare workers in primary healthcare facilities in an urban setting in Uganda.

We conducted a cross-sectional study among HCWs in private and public health facilities in Entebbe municipality between July 2021 and August 2021. Data was collected using a structured questionnaire that was shared, via an online link, to consented participants. Uptake of the vaccines among healthcare workers was analysed as proportions, and logistic regression was used to analyse barriers and facilitators to uptake of COVID-19 vaccines.

The study enrolled 360 participants, with 61.7% (n = 222) females. A total of 236 (65.6%) healthcare workers had received at least one dose of COVID-19 vaccine, with higher uptake among females 64% (n = 151). Age above 40 years (OR 2.16), working in a government healthcare facility (OR 3.12), participating in COVID-19 vaccine related activities (OR 4.62), and having tested for SARS-COV-2 (OR 3.05) increased the odds of having been vaccinated. Working in small roadside clinics reduced the odds of being vaccinated by almost 70%, while HCWs in government health services were 3.1 times more likely to have been vaccinated. History of having cared for a COVID-19 patient and having a positive SARS-COV-2 test result did not influence the uptake of the vaccines in the study population.

Vaccine uptake among HCWs was close to the World Health Organisation (WHO) recommended uptake of 70% by mid-2022.

It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT).

This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated.

Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes.

Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations.

Not applicable.

Determining the risk factors for severe disease and death among hospitalized Covid-19 patients is critical to optimize health outcomes and health services efficiency, especially in resource-constrained and humanitarian settings. This study aimed to identify the predictors of mortality of Covid-19 patients in North Kivu province in the Democratic Republic of Congo.A retrospective cohort study was conducted in 6 Covid-19 treatment centers in the city of Butembo from 1 January to 31 December 2021. The time to event (death), the outcome variable, was visualized by Kaplan-Meier curves and the log-rank test was used to confirm differences in trends. Cox regression was used for all the predictors in the bivariate analysis and multivariate analysis was done using predictors found statistically significant in the bivariate analysis. The following variables were considered for inclusion to the Cox regression model: Age, Sex, Disease length, Treatment site, History of at least one co-morbidity, Body mass index, Stage according to SpO2 and the NEWS-modified score.Among the 303 participants (mean age of 53 years), the fatality rate was 33.8 deaths per 1000 patient-days. Four predictors were independently associated with inpatient death: age category (≥ 60 years) (adjusted HR: 9.90; 95% CI: 2.68-36.27), presence of at least one comorbidity (adjusted HR: 11.39; 95% CI: 3.19-40.71); duration of illness of > 5 days before hospitalization (adjusted HR:1.70, 95% CI: 1.04-2.79) and peripheral capillary oxygen saturation (SpO2) < 90% (adjusted HR = 14.02, 95% CI: 2.23-88.32). In addition to advanced age, comorbidity, and length of disease before hospitalization, ambient air SpO2 measured by healthcare providers using low-tech, affordable and relatively accessible pulse oximetry could inform the care pathways of Covid-19 inpatients in resource-challenged health systems in humanitarian settings.

Biological sex differences refer to differences between males and females caused by the sex chromosome complement (that is, XY or XX), reproductive tissues (that is, the presence of testes or ovaries), and concentrations of sex steroids (that is, testosterone or oestrogens and progesterone). Although these sex differences are binary for most human individuals and mice, transgender individuals receiving hormone therapy, individuals with genetic syndromes (for example, Klinefelter and Turner syndromes) and people with disorders of sexual development reflect the diversity in sex-based biology. The broad distribution of sex steroid hormone receptors across diverse cell types and the differential expression of X-linked and autosomal genes means that sex is a biological variable that can affect the function of all physiological systems, including the immune system. Sex differences in immune cell function and immune responses to foreign and self antigens affect the development and outcome of diverse diseases and immune responses.

COVID-19 is associated with variable symptoms and clinical sequelae. Studies have examined the clinical course of these patients, finding a prolonged need for invasive ventilation and variable re-intubation rates. However, no research has investigated factors and outcomes related to re-intubation secondary to respiratory failure among patients with COVID-19 with ARDS.

We conducted a single-center, retrospective study on subjects intubated for ARDS secondary to COVID-19. The primary outcome was re-intubation status; secondary outcomes were hospital and ICU stay and mortality. Data were analyzed using between-group comparisons using chi-square testing for categorical information and Student t test for quantitative data. Univariate and multivariate logistic regression was performed to determine factors related to re-intubation and mortality as dependent variables.

One hundred and fourteen subjects were included, of which 32% required re-intubation. No between-group differences were detected for most demographic variables or comorbidities. No differences were detected in COVID-19 treatments, noninvasive respiratory support, mechanical circulatory support, or duration of ventilation. Midazolam (odds ratio [OR] 5.55 [95% CI 1.83-16.80], P = .002), fentanyl (OR 3.64 [95% CI 1.26-10.52], P = .02), and APACHE II scores (OR 1.08 [95% CI 1.030-1.147], P = .005) were independently associated with re-intubation (area under the curve = 0.81). Re-intubated subjects had extended hospital (36.7 ± 22.7 d vs 26.1 ± 12.1 d, P = .01) and ICU (29.6 ± 22.4 d vs 15.8 ± 10.4 d, P < .001) stays. More subjects died who failed extubation (49% vs 3%, P < .001). Age (OR 1.07 [95% CI 1.02-1.23], P = .005), male sex (OR 4.9 [95% CI 1.08-22.35], P = .041), positive Confusion Assessment Method for the ICU (CAM-ICU) (OR 5.43 [95% CI 1.58-18.62], P = .007), and re-intubation (OR 12.75 [95% CI 2.80-57.10], P < .001) were independently associated with death (area under the curve = 0.93).

Midazolam, fentanyl, and higher APACHE II scores were independently associated with re-intubation secondary to respiratory failure in subjects with COVID-19-related ARDS. Furthermore, age, male sex, positive CAM-ICU, and re-intubation were independently associated with mortality. Re-intubation also correlated with prolonged hospital and ICU stay.

Testosterone (T), the principal androgen secreted by the testes, plays an essential role in male health. Male hypogonadism is diagnosed based on a combination of associated clinical signs and symptoms and laboratory confirmation of low circulating T levels. In this review, we have highlighted factors, both biological and analytical, that introduce variation into the measurement of serum T concentrations in men; these need to be considered when requesting T levels and interpreting results. There is an ongoing need for analytical standardisation of T assays and harmonisation of pre- and post-analytical laboratory practices, particularly in relation to the laboratory reference intervals provided to clinicians. Further, there is a need to share with service users the most up-to-date and evidence-based action thresholds for serum T as recommended in the literature. Estimation of free testosterone may be helpful. Causes of secondary hypogonadism should be considered. A comprehensive approach is required in the management of male hypogonadism, including lifestyle modification as well as medication where appropriate. The goal of treatment is the resolution of symptoms as well as the optimisation of metabolic, cardiovascular, and bone health. The advice of an endocrinologist should be sought when there is doubt about the cause and appropriate management of the hypogonadism.

Cardiovascular disease is one of many risk factors that have been linked to increased severity or mortality in coronavirus disease 2019 (COVID-19) patients; however, the exact role of SARS-CoV-2 in the pathogenesis of cardiac inflammatory injury has not been established. A previous study reported that SARS-CoV-2 causes more severe disease with cardiomyopathy in a J2N-k animal model. Here, we investigated the sensitivity of J2N-k hamsters, as a cardiomyopathy animal model, to a delta strain of SARS-CoV-2 compared to J2N-n control animals. We found that J2N-k hamsters were less susceptible to this delta strain than J2N-n animals, and we found no evidence that cardiomyopathy is a risk factor in this animal model. Since the previous study reported that SARS-CoV-2 causes more severe disease with cardiomyopathy in the same animal model, further analysis of the relationship between cardiomyopathy and SARS-CoV-2 infection is needed.

COVID-19 vaccinations have reduced morbidity and mortality from the disease. Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) have been associated with immune protection. Seroprevalence studies revealed high immunoglobulin G (IgG) antibody levels to SARS-CoV-2 in the Pakistani population before vaccinations. We investigated the effect of BBIBP-CorV vaccination on circulating IgG antibodies and interferon (IFN)-γ from T cells measured in a cohort of healthy individuals, with respect to age, gender, and history of COVID-19.

The study was conducted between April and October 2021. BBIBP-CorV vaccinated participants were followed up to 24 weeks. Antibodies to SARS-CoV-2 Spike protein and its receptor-binding domain (RBD) were measured. IFNγ secreted by whole blood stimulation of Spike protein and extended genome antigens was determined.

Study participants with a history of prior COVID-19 displayed a higher magnitude of IgG antibodies to Spike and RBD. IgG seropositivity was greater in those with prior COVID-19, aged 50 years or younger and in females. At 24 weeks after vaccination, 37.4% of participants showed IFN-γ responses to SARS-CoV-2 antigens. T cell IFN-γ release was higher in those with prior COVID-19 and those aged 50 years or less. Highest IFN-γ release was observed to extended genome antigens in individuals both with and without prior COVID-19.

We found that IgG seropositivity to both Spike and RBD was affected by prior COVID-19, age and gender. Importantly, seropositive responses persisted up to 24 weeks after vaccination. Persistence of vaccine induced IgG antibodies may be linked to the high seroprevalence observed earlier in unvaccinated individuals. Increased T cell reactivity to Spike and extended genome antigens reflects cellular activation induced by BBIBP-CorV. COVID-19 vaccination may have longer lasting immune responses in populations with a higher seroprevalence. These data inform on vaccination booster policies for high-risk groups.

Post-COVID-19 syndromes have associated with female sex, but the pathophysiological basis is uncertain.

There are sex differences in myocardial inflammation identified using cardiac magnetic resonance (CMR) in post-COVID-19 patients, and in patient reported health outcomes following COVID-19 infection.

This prospective study investigated the time-course of multiorgan injury in survivors of COVID-19 during convalescence.

Clinical information, blood biomarkers, and patient reported outcome measures were prospectively acquired at enrolment (visit 1) and 28-60 days post-discharge (visit 2). Chest computed tomography (CT) and CMR were performed at visit 2. Follow-up was carried out for serious adverse events, including death and rehospitalization.

Sixty-nine (43%) of 159 patients recruited were female. During the index admission, females had a lower peak C-reactive protein (74 mg/l (21,163) versus 123 mg/l (70, 192) p = 0.008) and peak ferritin (229 μg/l (103, 551) versus 514 μg/l (228, 1122) p < 0.001). Using the Modified Lake-Louise criteria, females were more likely to have definite evidence of myocardial inflammation (54% (37/68) versus 33% (30/90) p = 0.003). At enrolment and 28-60 days post-discharge, enhanced illness perception, higher levels of anxiety and depression and lower predicted maximal oxygen utilization occurred more commonly in women. The mean (SD, range) duration of follow-up after hospital discharge was 450 (88) days (range 290, 627 days). Compared to men, women had lower rates of cardiovascular hospitalization (0% versus 8% (7/90); p = 0.018).

Women demonstrated worse patient reported outcome measures at index admission and 28-60 days follow-up though cardiovascular hospitalization was lower.

The COVID-19 pandemic has had a significant impact on every aspect of life, especially for healthcare professionals. Dentists are the most at risk of infection due to close contact with patients. This study aimed to assess the level of awareness, perception, and attitude of Palestinian dentists towards COVID-19 and infection control. A cross-sectional online survey was conducted from 17-30 July 2020, and 349 dentists from the West Bank participated. The survey assessed demographic variables, participation in infection control training, prevention methods used in dental clinics, patient preparation for dental work, cross-infection control and sterilization before and after the pandemic, and sources for guideline protocols for dental workers. The results of the study showed that 54 (14.4%) dentists had received training in infection control in dentistry and 121 (34.3%) had attended training specifically regarding COVID-19. During a partial lockdown, 60% of dentists treated only urgent cases. Overall, the dentists in the West Bank demonstrated good knowledge and a positive attitude towards COVID-19 and infection control measures in dental clinics, as there were significant differences between replacing a medical apron or mask and wearing a face shield, cover shoes, head cap, and goggles before and after COVID (p < 0.05). Moreover, there were significant differences between wrapping the chair and using purification devices to disinfect the clinic before and after COVID (p < 0.05). However, dentists' knowledge could be improved by increasing their accessibility to materials and provided training. Dental associations should provide guidelines regularly to dentists during a crisis to inform them of best practices and disease management. In conclusion, dentists need to update their knowledge, continuing education and training to guarantee the proper handling of COVID-19. The study's findings show the importance of updating infection control protocols and training programs that address the specific needs and challenges faced by dentists in the West Bank.

Pre-pandemic psychological distress is associated with increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but associations with the coronavirus disease 2019 (COVID-19) severity are not established. The authors examined the associations between distress prior to SARS-CoV-2 infection and subsequent risk of hospitalization.

Between April 2020 (baseline) and April 2021, we followed 54 781 participants from three ongoing cohorts: Nurses' Health Study II (NHSII), Nurses' Health Study 3 (NHS3), and the Growing Up Today Study (GUTS) who reported no current or prior SARS-CoV-2 infection at baseline. Chronic depression was assessed during 2010-2019. Depression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at baseline. SARS-CoV-2 infection and hospitalization due to COVID-19 was self-reported. Relative risks (RRs) were calculated by Poisson regression.

3663 participants reported a positive SARS-CoV-2 test (mean age = 55.0 years, standard deviation = 13.8) during follow-up. Among these participants, chronic depression prior to the pandemic [RR = 1.72; 95% confidence interval (CI) 1.20-2.46], and probable depression (RR = 1.81, 95% CI 1.08-3.03), being very worried about COVID-19 (RR = 1.79; 95% CI 1.12-2.86), and loneliness (RR = 1.81, 95% CI 1.02-3.20) reported at baseline were each associated with subsequent COVID-19 hospitalization, adjusting for demographic factors and healthcare worker status. Anxiety and perceived stress were not associated with hospitalization. Depression, worry about COVID-19, and loneliness were as strongly associated with hospitalization as were high cholesterol and hypertension, established risk factors for COVID-19 severity.

Psychological distress may be a risk factor for hospitalization in patients with SARS-CoV-2 infection. Assessment of psychological distress may identify patients at greater risk of hospitalization. Future work should examine whether addressing distress improves physical health outcomes.

In a retrospective analysis of 477 fatal COVID-19 cases hospitalised at a single medical centre during the period from 6 March 2020 to 30 June 2022, several factors defining those patients at admission were assessed, as well as the course of the hospitalisation and factors contributing to death. There was a predominance of men (59.3% (283)) burdened by comorbidities, with increased inflammation at admission. Patients aged ≥ 81 years were significantly more likely to be admitted to and die in infectious diseases units (IDU) due to respiratory failure, their hospital stays were shorter, and they were most likely not to receive specialist treatment. The most common COVID-19 complications included acute kidney injury in 31.2% (149) patients and thromboembolic complications in 23.5% (112). The course of hospitalisation was complicated by healthcare-associated infections (HAI) in 33.3% (159) of cases, more often in those treated with baricitinib (p < 0.001). The initial use of an antibiotic, although common (94.8% (452)), was unwarranted in almost half of the cases (47.6% (215)). Complications of hospitalisation (46.1% (220)) and adverse events involving staff (49.7% (237)) were found in almost half of the patients. In 88.7% (423) of the cases, death was due to respiratory failure in the course of SARS-CoV-2 infection. Adverse events during hospitalisation should be considered as an additional factor that, in addition to the infection itself, may have influenced the death of patients.

Sex related differences in the incidence or severity of infection have been described for multiple viruses. With herpes simplex viruses, the best example is HSV-2 genital infection where women have a higher incidence of infection and can have more severe infections than men. HSV-1 causes several types of infections including skin and mucosal ulcers, keratitis, and encephalitis in humans that do not appear to have a strong biological sex component. Given that mouse strains differ in their MHC loci it is important to determine if sex differences occur in multiple strains of mice. Our goal was to answer two questions: Are virus related sex differences present in BALB/C mice and does virulence of the viral strain have an effect? We generated a panel of recombinant HSV-1 viruses with differing virulence phenotypes and characterized multiple clinical correlates of ocular infection in BALB/c mice. We found no sex-specific differences in blepharitis, corneal clouding, neurovirulence, and viral titers in eye washes. Sex differences in neovascularization, weight loss and eyewash titers were observed for some recombinants, but these were not consistent across the phenotypes tested for any recombinant virus. Considering these findings, we conclude that there are no significant sex specific ocular pathologies in the parameters measured, regardless of the virulence phenotype following ocular infection in BALB/c mice, suggesting that the use of both sexes is not necessary for the bulk of ocular infection studies.

COVID-19 is a new pandemic, which was declared by the World Health Organization in 2019 as a threat to public health. According to numerous reports, it can have negative consequences for pregnant women, labour, and neonates born to infected mothers. The aim of this paper was to gather the evidence and to present a summary of the results of studies concerning COVID-19 in pregnant women and their neonates.

Articles from prestigious journals covering the period from 2020 to February 2023, relevant review papers, and original research articles from PubMed were analysed. In order to analyse the available research literature, the Web of Science, Scopus, and PubMed databases were used, in which the search for articles was conducted using terms ("pregnancy," "coronavirus," "SARS-CoV-2," and "newborn") and using PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analysis) guidelines for clinical trials. Meta-analyses and systematic reviews (2022-2023) on symptoms, neonatal course, and risk of COVID-19 infection have been summarized. Summary of meta-analyses and systematic reviews (2022-2023) on the effect and adverse reaction of the COVID-19 vaccination is presented.

As a result of the research conducted, it was confirmed that in most pregnant women, no serious signs of the infection were observed, although isolated cases of death related to COVID-19 in pregnant women were reported. Several authors called attention to the more severe course of the infection in pregnant women with obesity. It seemed that no vertical transmission from mother to child was occurring. Nevertheless, the information was not clinching. The condition of the neonates born to mothers with COVID-19 was in most cases described as normal; however, some papers reported deaths of infected neonates.

Due to insufficient data, further research is necessary. Further studies and follow-up are recommended, which would make possible an assessment of remote effects of COVID-19 on pregnancy and vital parameters of the newborn.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has affected all countries worldwide. Although some symptoms are relatively mild, others are still associated with severe and even fatal clinical outcomes. Innate and adaptive immunity are important for the control of SARS-CoV-2 infections, whereas a comprehensive characterization of the innate and adaptive immune response to COVID-19 is still lacking and the mechanisms underlying immune pathogenesis and host predisposing factors are still a matter of scientific debate. Here, the specific functions and kinetics of innate and adaptive immunity involved in SARS-CoV-2 recognition and resultant pathogenesis are discussed, as well as their immune memory for vaccinations, viral-mediated immune evasion, and the current and future immunotherapeutic agents. We also highlight host factors that contribute to infection, which may deepen the understanding of viral pathogenesis and help identify targeted therapies that attenuate severe disease and infection.

The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of SARS-CoV-2 has given rise to multiple variants with varying pathogenicity and transmissibility, such as the Delta and Omicron variants. Individuals with advanced age or underlying comorbidities, including hypertension, diabetes and cardiovascular diseases, are at a higher risk of increased disease severity. Hence, this has resulted in an urgent need for the development of better therapeutic and preventive approaches. This review describes the origin and evolution of human coronaviruses, particularly SARS-CoV-2 and its variants as well as sub-variants. Risk factors that contribute to disease severity and the implications of co-infections are also considered. In addition, various antiviral strategies against COVID-19, including novel and repurposed antiviral drugs targeting viral and host proteins, as well as immunotherapeutic strategies, are discussed. We critically evaluate strategies of current and emerging vaccines against SARS-CoV-2 and their efficacy, including immune evasion by new variants and sub-variants. The impact of SARS-CoV-2 evolution on COVID-19 diagnostic testing is also examined. Collectively, global research and public health authorities, along with all sectors of society, need to better prepare against upcoming variants and future coronavirus outbreaks.

Epidemiological studies have revealed sex differences in the incidence and morbidity of respiratory virus infection in the human population, and often these observations are correlated with sex differences in the quality or magnitude of the immune response. Sex differences in immunity and morbidity also are observed in animal models of respiratory virus infection, suggesting differential dominance of specific immune mechanisms. Emerging research shows intrinsic sex differences in immune cell transcriptomes, epigenomes, and proteomes that may regulate human immunity when challenged by viral infection. Here, we highlight recent research into the role(s) of sex steroids and X chromosome complement in immune cells and describe how these findings provide insight into immunity during respiratory virus infection. We focus on the regulation of innate and adaptive immune cells by receptors for androgen and estrogens, as well as genes with a propensity to escape X chromosome inactivation. A deeper mechanistic knowledge of these pathways will help us to understand the often significant sex differences in immunity to endemic or pandemic respiratory pathogens such as influenza viruses, respiratory syncytial viruses and pathogenic coronaviruses.

Liver injury occurs frequently as a consequence of SARS-CoV-2 infection. Direct infection of the liver leads to hepatic impairment with elevated transaminases. In addition, severe COVID-19 is characterized by cytokine release syndrome, which may initiate or exacerbate liver injury. In patients with cirrhosis, SARS-CoV-2 infection is associated with acute-on-chronic liver failure. The Middle East and North Africa (MENA) region is one of the world's regions characterized by a high prevalence of chronic liver diseases. Both parenchymal and vascular types of injury contribute to liver failure in COVID-19, with a myriad of pro-inflammatory cytokines playing a major role in perpetuating liver injury. Additionally, hypoxia and coagulopathy complicate such a condition. This review discusses the risk factors, and the underlying causes of impaired liver functions in COVID-19, with a focus on key players in the pathogenesis of liver injury. It also highlights the histopathological changes encountered in postmortem liver tissues as well as potential predictors and prognostic factors of such injury, in addition to the management strategies to ameliorate liver damage.

Significant efforts and initiatives were already made in the health care systems, however in the last few years; our world is facing emergences of viral infections which potentially leading to considerable challenges in terms of higher morbidity, mortality, increased and considerable financial loads on the affected populations. Over ten major epidemics or pandemics have been recorded in the twenty-first century, the ongoing coronavirus pandemic being one of them. Viruses being distinct obligate pathogens largely dependent on living beings are considered as one of the prominent causes of death globally. Although effective vaccines and antivirals have led to the eradication of imperative viral pathogens, the emergences of new viral infections as well as novel drug-resistant strains have necessitated the implementation of ingenious and efficient therapeutic approaches to treat viral outbreaks in the future. Nature being a constant source of tremendous therapeutical resources has inspired us to develop multi-target antiviral drugs, overcoming the challenges and limitations faced by pharmaceutical industry. Recent breakthroughs in the understanding of the cellular and molecular mechanisms of viral reproduction have laid the groundwork for potential treatment approaches including antiviral gene therapy relying on the application of precisely engineered nucleic acids for disabling pathogen replication. The development of RNA interference and advancements in genome manipulating tools have proven to be especially significant in this regard. In this review, we discussed mode of actions and pathophysiological events associated with the viral infections; followed by distributions, and advancement made towards the detection strategies for timely diagnosis. In the later section, current approaches to cope up the viral pathogens and their key limitations have also been elaborated. Lastly, we also explored some novel and potential targets to treat such infections, where attentions were made on next generation gene editing technologies.

Although androgen in gender disparity of COVID-19 has been implied, no direct link has been provided.

Here, we applied AlphaFold multimer, network and single cells database analyses to highlight specificity of Androgen receptor (AR) against spike receptor binding protein (RBD) of SARS-CoV-2.

LXXL motifs in spike RBD are essential for AR binding. RBD LXXA mutation complex with the AR depicting slightly reduced binding energy, as LXXLL motif usually mediates nuclear receptor binding to coregulators. Moreover, AR preferred to bind a LYRL motif in specificity and interaction interface, and showed reduced affinity against Omicron compared to other variants (alpha, beta, gamma, and delta). Importantly, RBD LYRL motif is a conserved antigenic epitope (9 residues) for T-cell response. Network analysis of AR-related genes against COVID-19 database showed T-cell signaling regulation, and CD8+ T-cell spatial location in AR+ single cells, which is consistent with the AR binding motif LYRL in epitope function.

We provided the potent mechanisms of AR binding to RBD linking to immune response and vaccination shift. AR could be an anti-infective therapy target for anti-Omicron new lineages.

Geroscience puts mechanisms of aging as a driver of the most common age-related diseases and dysfunctions. Under this perspective, addressing the basic mechanisms of aging will produce a better understanding than addressing each disease pathophysiology individually. Worldwide, despite greater functional impairment, life expectancy is higher in women than in men. Gender differences in the prevalence of multimorbidity lead mandatory to the understanding of the mechanisms underlying gender-related differences in multimorbidity patterns and disability-free life expectancy. Extensive literature suggested that inflammaging is at the crossroad of aging and age-related diseases. In this review, we highlight the main evidence on sex/gender differences in the mechanisms that foster inflammaging, i.e. the age-dependent triggering of innate immunity, modifications of adaptive immunity, and accrual of senescent cells, underpinning some biomarkers of inflammaging that show sex-related differences. In the framework of the "gender medicine perspective", we will also discuss how sex/gender differences in inflammaging can affect sex differences in COVID-19 severe outcomes.

In early 2020, the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, and rapidly propagated worldwide causing a global health emergency. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) protein for cell entry, followed by proteolytic cleavage of the Spike (S) protein by the transmembrane serine protease 2 (TMPRSS2), allowing fusion of the viral and cellular membranes. Interestingly, TMPRSS2 is a key regulator in prostate cancer (PCa) progression which is regulated by androgen receptor (AR) signaling. Our hypothesis is that the AR signaling may regulate the expression of TMPRSS2 in human respiratory cells and thus influence the membrane fusion entry pathway of SARS-CoV-2. We show here that TMPRSS2 and AR are expressed in Calu-3 lung cells. In this cell line, TMPRSS2 expression is regulated by androgens. Finally, pre-treatment with anti-androgen drugs such as apalutamide significantly reduced SARS-CoV-2 entry and infection in Calu-3 lung cells but also in primary human nasal epithelial cells. Altogether, these data provide strong evidence to support the use of apalutamide as a treatment option for the PCa population vulnerable to severe COVID-19.

The role of steroid hormones against infectious diseases has been extensively studied. From immunomodulatory action to direct inhibition of microorganism growth, hormones D3 (VD3) and 17β-estradiol (E2), and the genetic pathways modulated by them, are key targets for a better understanding pathogenesis of infectious respiratory diseases (IRD) such as tuberculosis (TB) and the coronavirus disease-19 (COVID-19). Currently, the world faces two major public health problems, the outbreak of COVID-19, accounting for more than 6 million so far, and TB, more than 1 million deaths per year. Both, although resulting from different pathogens, the Mtb and the SARS-CoV-2, respectively, are considered serious and epidemic. TB and COVID-19 present similar infection rates between men and women, however the number of complications and deaths resulting from the two infections is higher in men when compared to women in childbearing age, which may indicate a role of the sex hormone E2 in the context of these diseases. E2 and VD3 act upon key gene pathways as important immunomodulatory players and supporting molecules in IRDs. This review summarizes the main roles of these hormones (VD3 and E2) in modulating immune and inflammatory responses and their relationship with TB and COVID-19.