Levels of plant-based aeroallergens are rising as growing seasons lengthen and intensify with anthropogenic climate change. Increased exposure to pollens could increase risk for mortality from respiratory causes, particularly among older adults. We determined short-term, lag associations of four species classes of pollen (ragweed, deciduous trees, grass pollen and evergreen trees) with respiratory mortality (all cause, chronic and infectious related) in Michigan, USA.

We obtained records for all Michigan deaths from 2006-2017 from the Michigan Department of Health and Human Services (MDHHS). Deaths from infectious and chronic respiratory-related causes were selected using International Classification of Diseases (ICD-10) codes. Pollen data were obtained from a prognostic model of daily pollen concentrations at 25 km resolution. Case-crossover models with distributed lag non-linear crossbases for pollen were used to estimate associations between lags of daily pollen concentrations with mortality and to explore effect modification by sex and racial groups.

127,163 deaths were included in the study. Cumulative daily high concentrations (90th percentile) of deciduous broadleaf, grass and ragweed were associated with all-cause respiratory mortality at early lags with e.g., a 1.81 times higher risk of all respiratory deaths at cumulative 7 day lag exposure to deciduous broadleaf pollen at the 90th percentile (95% confidence interval: 1.04, 3.15). Exposure to high concentrations of grass and ragweed pollens was associated with increased risk for death from chronic respiratory causes. No association was found for any pollen species with death from infectious respiratory causes though there was a positive but non-significant association of exposure to deciduous broadleaf and ragweed pollens. We found no evidence to suggest effect modification by race or sex.

Modelled exposures to high concentrations of pollen taxa were associated with increased all-cause and chronic respiratory mortality among older adults. Results suggest that pollen exposure may become more important to respiratory mortality as the temperatures increase and pollen seasons lengthen.

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.

Since the beginning of the COVID-19 pandemic, in Brazil, there has been a high rate of deaths, mainly among those who were hospitalised due to the disease and those who needed intensive care units (ICUs) and mechanical ventilation support.

The study evaluated the hospitalised patients with COVID-19 as well as subgroups considering those hospitalised patients who needed ICU treatment and those who received invasive mechanical ventilation in an ICU. The risk of death was compared in these three groups with adjustments for gender, age, race and comorbidities. A multivariable analysis was performed to identify the main predictors of death. A hospitalised patient was considered COVID-19 positive if they had a positive real-time polymerase chain reaction (RT-PCR) or serological test, followed by a notification form completed by a health professional, usually a medical doctor. The study was approved by the ethics committee of the institution (Certificate of Presentation of Ethical Appreciation n° 67241323.0.0000.5514; Study Approval Technical Opinion n° 5.908.611).

The study evaluated 2 031 309 hospitalised individuals with COVID-19. The case fatality rate was 33.2% (673 527/2 031 309). The case fatality rate was even higher among those patients who required ICU (372 031/665 621; 55.9%) treatment with the need for invasive ventilation support (240 704/303 505; 79.3%). In the multivariable analysis, the male sex (OR=1.14; 95% CI=1.13-1.15), older age [61 to 72 years old (OR=2.43; 95% CI=2.41-2.46), 83 to 85 years old (OR=4.10; 95% CI=4.06-4.14) and+85 years (OR=6.98; 95% CI=6.88-7.07)], race [mixed individuals (Pardos) (OR=1.33; 95% CI=1.32-1.34), Black people (OR=1.57; 95% CI=1.55-1.60) and Indigenous peoples (OR=1.82, 95% CI=1.69-1.97)] and the presence of comorbidities [mainly, hepatic disorder (OR=1.80; 95% CI=1.73-1.87), immunosuppressive disorder (OR=1.80; 95% CI=1.76-1.84) and kidney disorder (OR=1.67; 95% CI=1.64-1.70)] were associated with an increased chance of death, except asthma (OR=0.77; 95% CI=0.75-0.79). In addition, among all admitted patients with COVID-19, the need for an ICU (OR=2.08; 95% CI=2.06-2.13) and invasive ventilatory support (OR=14.86; 95% CI=14.66-15.05) had an impact on death as an outcome.

Although the number of daily deaths from the coronavirus dropped during the COVID-19 pandemic in Brazil, our retrospective analysis showed a higher case fatality rate in patients requiring ICU, mainly when using invasive ventilation, compared with the rest of the world.

The global number of COVID-19 deaths has reached 7 million, with 4% of these deaths occurring in children and adolescents. In Brazil, around 1500 children up to 11 years old died from the disease. The most common symptoms in children are respiratory, potentially progressing to severe illnesses, such as severe acute respiratory syndrome (SARS) and MIS-C. Studies indicate that comorbidities and genetic factors, such as polymorphisms in immune response genes, can influence the severity of COVID-19. This study investigates the occurrence of single-nucleotide polymorphisms (SNPs) in innate immune response genes in children with COVID-19. Seventy-three samples were analyzed from children under 13 years old hospitalized at João Paulo II Children's Hospital due to COVID-19. The evaluated SNPs were tlr8 (1) (rs3764879), tlr8 (2) (rs2407992), tlr7 (rs179008), tlr3 (rs3775291), tirap (rs8177374), and mcp-1 (rs1024611), considering four categories of severity: mild, moderate, severe, and critical COVID-19. To identify the SNPs, PCR and sequencing were performed. The frequencies of the SNPs obtained were not discrepant when compared to the frequencies described in the Global ALFA, Global 1000 Genomes, Global gnomAD, American 1000 Genomes, and American gnomAD databases, except for the SNP in TLR7. Comparing severe and critical cases to mild and moderate cases, we found a higher relative risk associated with mutations in tlr8 (1), tlr7, tlr3, and tirap (p < 0.05). No association was found for SNPs in tlr8 (2) and mcp-1. Our analyses suggest an association between SNPs in innate immune response genes and severity of symptoms in children with COVID-19 (or SARS-CoV-2 infected children).

Background: The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (dNLR), neutrophil-to-lymphocyte and platelet ratio (N/LP ratio), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and systemic inflammation index (SII) have emerged as noteworthy determinants in evaluating the severity and mortality prognosis of inflammatory diseases. In order to predict mortality rate, this study aimed to assess the impact of systemic inflammatory markers on both men and women who were admitted to the hospital due to SARS-CoV-2 infection. Methods: The laboratory parameters of the 2007 COVID-19 patients were analyzed in a retrospective study (men = 1145 and women = 862). Receiver operating characteristic (ROC) analysis was used to determine the capability of inflammatory markers to differentiate the severity of COVID-19, while survival probability was determined using Kaplan-Meier curves, with the endpoint being death. To prevent any linear bias, the inflammatory indices were assessed separately using univariate analysis for Charlson comorbidity index (CCI), and adjustments were made for confounding factors if p < 0.2. Results: Adjusted-NLR, adjusted-MLR, N/LP ratio, adjusted-dNLR, adjusted-AISI, adjusted-SII, and adjusted-SIRI exhibited remarkably higher values in patients who did not survive as compared to those who did. The multivariate Cox regression models demonstrated significant association between survival and N/LP ratio (HR = 1.564, 95% CI = 1.161 to 2.107, p < 0.01) in men and N/LP ratio (HR = 1.745, 95% CI = 1.230 to 2.477, p < 0.01) and adjusted-SII (HR = 6.855, 95% CI = 1.454 to 32.321, p < 0.05) in women. Conclusion: A reliable predictor in the current study of men and women with COVID-19 was N/LP ratio.

COVID-19 is characterised by a wide variety of clinical manifestations, and clinical tests and genetic analysis might help to predict patient outcomes.

In the current study, the expression of genes related to immune response (CCL5, IFI6, OAS1, IRF9, IL1B, and TGFB1) was analysed in the upper airway and paired-blood samples from 25 subjects infected with SARS-CoV-2. Relative gene expression was determined by RT-qPCR.

CCL5 expression was higher in the blood than in the upper airway (p < 0.001). In addition, a negative correlation was found between IFI6 and viral load (p = 0.033) in the upper airway, suggesting that the IFI6 expression inhibits the viral infection. Concerning sex, women expressed IL1B and IRF9 in a higher proportion than men at a systemic level (p = 0.008 and p = 0.049, respectively). However, an increased expression of IRF9 was found in men compared to women in the upper airway (p = 0.046), which could be due to the protective effect of IRF9, especially in men.

The higher expression of CCL5 in blood might be due to the key role of this gene in the migration and recruitment of immune cells from the systemic circulation to the lungs. Our findings confirm the existence of sex differences in the immune response to early stages of the infection. Further studies in a larger cohort are necessary to corroborate the current findings.

COVID-19 is an infectious disease that caused a global pandemic in 2020. In the critical moments of this healthcare emergencies, the medical staff needs to take important decisions in a context of limited resources that must be carefully managed. To this end, the computer-aided diagnosis methods are extremely powerful and help them to better recognize the evidences of high-risk patients. This can be done with the support of relevant information extracted from electronic health records, lab tests and imaging studies. In this work, we present a novel fully-automatic efficient method to help the clinical decision-making process in the context of COVID-19 risk estimation, using multimodal data fusion of clinical features and deep features extracted from chest X-ray images. The risk estimation is studied in two of the most relevant and critical encountered scenarios: the risk of hospitalization and mortality. This study shows which are the most important features for each scenario, the ratio of clinical and imaging features present in the top ranking and the performance of the used machine learning models. The results demonstrate a great performance by the classifiers, estimating the risk of hospitalization with an AUC-ROC of 0.8452 ± 0.0133 and the risk of death with an AUC-ROC of 0.8285 ± 0.0210, only using a subset of the original features, and highlight the significant contribution of imaging features to hospitalization risk assessment, while clinical features become more crucial for mortality risk evaluation. Furthermore, multimodal data fusion can outperform the approaches that use one data source. Despite the model's complexity, it requires fewer features, an advantage in scenarios with limited computational resources. This streamlined, fully-automated method shows promising potential to improve the clinical decision-making process and better manage medical resources, not only in the context of COVID-19, but also in other clinical scenarios.

IL-26 is a key mediator of pulmonary host defense given its abundant expression in human airways and its established antibacterial properties. Moreover, recent studies indicate that IL-26 can also inhibit viral replication. Along these lines, we have previously reported an increase in the plasma concentration of IL-26 among patients with acute COVID-19 that is linked to harmful hyperinflammation. Nevertheless, it is still unclear whether this systemic increase in IL-26 relates to disease severity, sex, comorbidities, viral load, or the innate immune response in acute COVID-19.

IL-26 was quantified using ELISA in plasma samples from a large cohort of well-characterized patients with acute COVID-19 (n=178) and healthy controls (n=30). The plasma concentrations of SARS-CoV-2 nucleocapsid and spike protein, as well as those of IFN-α2a, IFN-β, and IFN-γ, were determined using electrochemiluminescence immunoassay. The concentration of double-stranded DNA was determined using fluorometry.

The plasma concentration of IL-26 was increased in patients with severe/critical COVID-19, particularly among males and patients with comorbid obstructive lung disease. Moreover, the concentration of IL-26 displayed positive correlations with length of hospital stay, as well as with systemic markers of viral load, antiviral immunity, and extracellular DNA.

Systemic IL-26 is involved in severe COVID-19, especially in males and patients with comorbid obstructive lung disease. These findings argue that systemic IL-26 has pathogenic and antiviral relevance, as well as biomarker potential.

The SARS-CoV-2 Omicron variant is characterized by its high transmissibility, which has caused a worldwide epidemiological event. Yet, it turns ominous once the disease progression degenerates into severe pneumonia and sepsis, presenting a horrendous lethality. To elucidate the alveolar immune or inflammatory landscapes of Omicron critical-ill patients, we performed single-cell RNA-sequencing (scRNA-seq) of bronchoalveolar lavage fluid (BALF) from the patients with critical pneumonia caused by Omicron infection, and analyzed the correlation between the clinical severity scores and different immune cell subpopulations. In the BALF of Omicron critical patients, the alveolar violent myeloid inflammatory environment was determined. ISG15+ neutrophils and CXCL10+ macrophages, both expressed the interferon-stimulated genes (ISGs), were negatively correlated with clinical pulmonary infection score, while septic CST7+ neutrophils and inflammatory VCAN+ macrophages were positively correlated with sequential organ failure assessment. The percentages of ISG15+ neutrophils were associated with more protective alveolar epithelial cells, and may reshape CD4+ T cells to the exhaustive phenotype, thus preventing immune injuries. The CXCL10+ macrophages may promote plasmablast/plasma cell survival and activation as well as the production of specific antibodies. As compared to the previous BALF scRNA-seq data from SARS-CoV-2 wild-type/Alpha critical patients, the subsets of neutrophils and macrophages with pro-inflammatory and immunoregulatory features presented obvious distinctions, suggesting an immune disparity in Omicron variants. Overall, this study provides a BALF single-cell atlas of Omicron critical patients, and suggests that alveolar interferon-responsive neutrophils and macrophages may extricate SARS-CoV-2 Omicron critical patients from the nasty fate of sepsis.

The liver, the largest organ in the human body, plays a multifaceted role in digestion, coagulation, synthesis, metabolism, detoxification, and immune defense. Changes in liver function often coincide with disruptions in both the central and peripheral nervous systems. The intricate interplay between the nervous and immune systems is vital for maintaining tissue balance and combating diseases. Signaling molecules and pathways, including cytokines, inflammatory mediators, neuropeptides, neurotransmitters, chemoreceptors, and neural pathways, facilitate this complex communication. They establish feedback loops among diverse immune cell populations and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems within the liver. In this concise review, we provide an overview of the structural and compositional aspects of the hepatic neural and immune systems. We further explore the molecular mechanisms and pathways that govern neuroimmune communication, highlighting their significance in liver pathology. Finally, we summarize the current clinical implications of therapeutic approaches targeting neuroimmune interactions and present prospects for future research in this area.

COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction.

This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention.

An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized.

The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection.

Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses.

The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare in the United States.

To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease (IBD) decedents.

We performed a register-based study using data from the National Vital Statistics System, which reports death data from over 99% of the United States population, from January 1, 2006 through December 31, 2021. IBD-related deaths among adults 25 years and older were stratified by age, sex, race/ethnicity, place of death, and primary cause of death. Predicted and actual age-standardized mortality rates (ASMRs) per 100000 persons were compared.

49782 IBD-related deaths occurred during the study period. Non-COVID-19-related deaths increased by 13.14% in 2020 and 18.12% in 2021 [2020 ASMR: 1.55 actual vs 1.37 predicted, 95% confidence interval (CI): 1.26-1.49; 2021 ASMR: 1.63 actual vs 1.38 predicted, 95%CI: 1.26-1.49]. In 2020, non-COVID-19-related mortality increased by 17.65% in ulcerative colitis (UC) patients between the ages of 25 and 65 and 36.36% in non-Hispanic black (NHB) Crohn's disease (CD) patients. During the pandemic, deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased.

IBD patients suffered excess non-COVID-19-related death during the pandemic. Excess death was associated with younger age among UC patients, and with NHB race among CD patients. Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

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.

Since there are currently no specific SARS-CoV-2 prognostic viral biomarkers for predicting disease severity, there has been interest in using SARS-CoV-2 polymerase chain reaction (PCR) cycle-threshold (Ct) values to predict disease progression.

This study assessed the association between in-hospital mortality of hospitalized COVID-19 cases and Ct-values of gene targets specific to SARS-CoV-2.

Clinical data of hospitalized COVID-19 cases from Gauteng Province from April 2020-July 2022 were obtained from a national surveillance system and linked to laboratory data. The study period was divided into pandemic waves: Asp614Gly/wave1 (7 June-22 Aug 2020); beta/wave2 (15 Nov 2020-6 Feb 2021); delta/wave3 (9 May-18 Sept 2021) and omicron/wave4 (21 Nov 2021-22 Jan 2022). Ct-value data of genes specific to SARS-CoV-2 according to testing platforms (Roche-ORF gene; GeneXpert-N2 gene; Abbott-RdRp gene) were categorized as low (Ct < 20), mid (Ct20-30) or high (Ct > 30).

There were 1205 recorded cases: 836(69.4%; wave1), 122(10.1%;wave2) 21(1.7%; wave3) and 11(0.9%;in wave4). The cases' mean age(±SD) was 49 years(±18), and 662(54.9%) were female. There were 296(24.6%) deaths recorded: 241(81.4%;wave1), 27 (9.1%;wave2), 6 (2%;wave3), and 2 (0.7%;wave4) (p < 0.001). Sample distribution by testing platforms was: Roche 1,033 (85.7%), GeneXpert 169 (14%) and Abbott 3 (0.3%). The median (IQR) Ct-values according to testing platform were: Roche 26 (22-30), GeneXpert 38 (36-40) and Abbott 21 (16-24). After adjusting for sex, age and presence of a comorbidity, the odds of COVID-19 associated death were high amongst patients with Ct values 20-30[adjusted Odds Ratio (aOR) 2.25; 95% CI: 1.60-3.18] and highest amongst cases with Ct-values <20 (aOR 3.18; 95% CI: 1.92-5.27), compared to cases with Ct-values >30.

Although odds of COVID19-related death were high amongst cases with Ct-values <30, Ct values were not comparable across different testing platforms, thus precluding the comparison of SARS-CoV-2 Ct-value results.

Our aim was to highlight the clinical characteristics and determine the risk factors associated with severe and non-severe COVID-19 infection.

A retrospective review was conducted on clinical data obtained from patients with COVID-19 infection, admitted to the emergency department between November 2022 and January 2023. Total of 1684 participants were categorized into severe (312 cases,18.53%) and non-severe (1,372 cases,81.47%) cohorts. Logistic regression was utilized for multivariate analysis, with a P-value less than 0.05 signifying a significant difference between the groups.

The study consisted of 952 males (56.53%) and 732 females (43.47%) participants. The age distribution ranged from 18 to 93 years in both cohorts. There were statistically significant differences between the clinical symptoms of the severe and non-severe cohorts (P < 0.05). According to the multivariate statistical analysis, patients with more pronounced clinical manifestations had significantly elevated values related to age(P < 0.05), diabetes(P < 0.01), hypertension(P < 0.01), C-reactive protein (CRP) (P < 0.05), and lactate dehydrogenase (LDH) (P < 0.01) as compared to those presenting with milder symptoms.

The primary clinical presentations in both the cohorts were mostly similar. Predominant factors contributing to the severity of COVID-19 infection were age, diabetes, hypertension, elevated CRP levels, and increased LDH.

In clinical practice, we observed an apparent overrepresentation of COVID-19 patients on anti-CD20 monoclonal antibody therapy. The aim of this study was to characterize the clinical picture of COVID-19 in these patients.

All adult patients from Turku University Hospital, Turku, Finland, with COVID-19 diagnosis and/or positive SARS-CoV-2 PCR test result up to March 2023, and with anti-CD20 therapy within 12 months before COVID-19 were included. Data was retrospectively obtained from electronic patient records.

Ninety-eight patients were identified. 44/93 patients (47.3%) were hospitalized due to COVID-19. Patients with demyelinating disorder (n = 20) were youngest (median age 36.5 years, interquartile range 33-45 years), had less comorbidities, and were least likely to be hospitalized (2/20; 10.0%) or die (n = 0). COVID-19 mortality was 13.3% in the whole group, with age and male sex as independent risk factors. Persistent symptoms were documented in 33/94 patients (35.1%) alive by day 30, in 21/89 patients (23.6%) after 60 days, and in 15/85 after 90 days (17.6%), mostly in patients with haematological malignancy or connective tissue disease. Prolonged symptoms after 60 days predisposed to persistent radiological findings (odds ratio 64.0; 95% confidence interval 6.3-711; p < 0.0001) and persistently positive PCR (odds ratio 45.5, 95% confidence interval 4.0-535; p < 0.0001). Several patients displayed rapid response to late antiviral therapy.

Anti-CD20 monoclonal antibody therapy is associated with high COVID-19 mortality and with a phenotype consistent with prolonged viral pneumonia. Our study provides rationale for retesting of immunocompromised patients with prolonged COVID-19 symptoms and considering antiviral therapy.

Currently, sequencing has been the only tool for the identification of circulating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants. However, it is known to be an expensive and laborious approach involving high technical expertise. Considering the reduced adherence to preventive measures postlockdown in Accra, this study presents an alternative method that leverages polymerase chain reaction (PCR) to identify circulating SARS-CoV-2 variants in the Accra Metropolis postlockdown.

This prospective cross-sectional study was conducted between July and December 2022. Nasopharyngeal samples were collected from 268 consenting participants. Samples were subjected to nucleic acid extraction and followed by real-time polymerase chain reaction for the detection and quantification of SARS-CoV-2 RNA. SARS-CoV-2 positive samples were subsequently subjected to variant identification using rapid PCR. Findings. The prevalence of SARS-CoV-2 within the Accra Metropolis was 30.2%. The majority of the SARS-CoV-2 infection was diagnosed in females, participants aged 41-50 years, and symptomatic participants. Participants aged ≤10 years and females recorded the highest viral load while participants aged 41-50 years recorded the highest number of infections. The SARS-CoV-2 variants detected were Alpha (64.2%), Delta (22.2%), and Omicron (13.6%). Predictors of SARS-CoV-2 infection identified were chills, cough, headache, body weakness, sore throat, and dyspnoea in order of decreasing association with SARS-CoV-2 infection. There was a strong association between symptom status, gender, age, and SARS-CoV-2 infection.

There was a high prevalence of SARS-CoV-2 within the Accra Metropolis postlockdown within the sampling period. The Alpha variant of SARS-CoV-2 is the predominant circulating variant, and persons presenting with symptoms are most likely to be diagnosed with COVID-19. Children aged ≤10 years serve as a reservoir for infection transmission.

The world has witnessed one of the largest pandemics, dubbed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of December 2020, the USA alone reported 98,948 cases of coronavirus disease 2019 (COVID-19) infection during pregnancy, with 109 related maternal deaths. Current evidence suggests that unvaccinated pregnant women infected with SARS-CoV-2 are at a higher risk of experiencing complications related to COVID-19 compared to nonpregnant women. This review aimed to provide healthcare workers and non-healthcare workers with a comprehensive overview of the available information regarding the efficacy of vaccines in pregnant women.

We performed a systematic review and meta-analysis following PRISMA guidelines. The search through the database for articles published between December 2019 and October 2021 was performed. A comprehensive search was performed in PubMed, Scopus, and EMBASE databases for research publications published between December 2019 and October 2021. We focused on original research, case reports, case series, and vaccination side effect by authoritative health institutions. Phrases used for the Medical Subject Heading [MeSH] search included ("COVID-19" [MeSH]) or ("Vaccine" [MeSH]) and ("mRNA" [MeSH]) and ("Pregnant" [MeSH]). Eleven studies were selected and included, with a total of 46,264 pregnancies that were vaccinated with mRNA-containing lipid nanoparticle vaccine from Pfizer/BioNTech and Moderna during pregnancy. There were no randomized trials, and all studies were observational (prospective, retrospective, and cross-sectional). The mean maternal age was 32.2 years, and 98.7% of pregnant women received the Pfizer COVID-19 vaccination. The local and systemic adverse effects of the vaccination in pregnant women were analyzed and reported. The local adverse effects of the vaccination (at least 1 dose) such as local pain, swelling, and redness were reported in 32%, 5%, and 1%, respectively. The systemic adverse effects such as fatigue, headaches, new onset or worsening of muscle pain, chills, fever, and joint pains were also reported in 25%, 19%, 18%, 12%, 11%, and 8%, respectively. The average birthweight was 3,452 g. Among these pregnancies, 0.03% were stillbirth and 3.68% preterm (<37 weeks) births.

The systemic side effect profile after administering the COVID-19 mRNA vaccine to pregnant women was similar to that in nonpregnant women. Maternal and fetal morbidity and mortality were lowered with the administration of either one or both the doses of the mRNA COVID-19 vaccination.

The Omicron variant has rapidly spread throughout the world compared to the Delta variant and poses a great threat to global healthcare systems due to its immune evasion and rapid spread. Sex has been identified as a factor significantly associated with COVID-19 mortality, but it remains unclear which clinical indicators could be identified as risk factors in each sex group and which sex-specific risk factors might shape the worse clinical outcome, especially for Omicrons. This study aimed to confirm the relationship between sex and the progression of the Omicron variant and to explore its sex-biased risk factors.

We conducted a retrospective study including 1,132 hospitalized patients with the COVID-19 Omicron variant from 5 December 2022 to 25 January 2023 at Shanghai General Hospital, and the medical history data and clinical index data of the inpatients for possible sex differences were compared and analyzed. Then, a sex-specific Lasso regression was performed to select the variables significantly associated with critical illness, including intensive care unit admission, invasive mechanical ventilation, or death. A logistic regression was used to construct a sex-specific predictive model distinctively for the critical illness outcome using selected covariates.

Among the collected 115 clinical indicators, up to 72 showed significant sex differences, including the difference in merit and the proportion of people with abnormalities. More importantly, males had greater critical illness (28.4% vs. 19.9%) and a significantly higher intensive care unit occupancy (20.96% vs. 14.49%) and mortality (13.2% vs. 4.9%), and males over 80 showed worse outcomes than females. Predictive models (AUC: 0.861 for males and 0.898 for females) showed 12 risk factors for males and 10 for females. Through a comprehensive sex-stratified analysis of a large cohort of hospitalized Omicron-infected patients, we identified the specific risk factors for critical illness by developing prediction models.

Sex disparities and the identified risk factors should be considered, especially in the personalized prevention and treatment of the COVID-19 Omicron variant.

The COVID-19 pandemic's uneven impact on subnational regions highlights the importance of understanding its local-level mortality impact. Vital statistics are available for an increasing number of countries for 2020, 2021, and 2022, facilitating the computation of subnational excess mortality and a more comprehensive assessment of its burden. However, this calculation faces two important methodological challenges: it requires appropriate mortality projection models; and small populations imply considerable, though commonly neglected, uncertainty in the estimates. We address both issues using a method to forecast mortality at the subnational level, which incorporates uncertainty in the computation of mortality measures. We illustrate our approach by examining French départements (NUTS 3 regions, or 95 geographical units), and produce sex-specific estimates for 2020. This approach is highly flexible, allowing one to estimate excess mortality during COVID-19 in most demographic scenarios and for past pandemics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with enhanced transmissibility and immune escape have emerged periodically throughout the coronavirus disease 2019 (COVID-19) pandemic, but the impact of these variants on disease severity has remained unclear. In this single-center, retrospective cohort study, we examined the association between SARS-CoV-2 clade and patient outcome over a two-year period in Chicago, Illinois. Between March 2020 and March 2022, 14,252 residual diagnostic specimens were collected from SARS-CoV-2-positive inpatients and outpatients alongside linked clinical and demographic metadata, of which 2,114 were processed for viral whole-genome sequencing. When controlling for patient demographics and vaccination status, several viral clades were associated with risk for hospitalization, but this association was negated by the inclusion of population-level confounders, including case count, sampling bias, and shifting standards of care. These data highlight the importance of integrating non-virological factors into disease severity and outcome models for the accurate assessment of patient risk.

In 2019, the breakthrough of the coronavirus 2 disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represented one of the major issues of our recent history. Different drugs have been tested to rapidly find effective anti-viral treatments and, among these, antiandrogens have been suggested to play a role in mediating SARS-CoV-2 infection. Considering the high heterogeneity of studies on this topic, we decided to review the current literature.

We performed a systematic review according to PRISMA guidelines. A search strategy was conducted on PUBMED and Medline. Only original articles published from March 2020 to 31 August 2023 investigating the possible protective role of antiandrogens were included. In vitro or preclinical studies and reports not in the English language were excluded. The main objective was to investigate how antiandrogens may interfere with COVID-19 outcomes.

Among 1755 records, we selected 31 studies, the majority of which consisted of retrospective clinical data collections and of randomized clinical trials during the first and second wave of the COVID-19 pandemic.

In conclusion, we can state that antiandrogens do not seem to protect individuals from SARS-CoV-2 infection and COVID-19 severity and, thus, their use should not be encouraged in this field.

Coronavirus disease (COVID-19) has posed a significant threat to the lives and health of people worldwide since its onset in 2019. However, the relationship between the number of vaccination shots and the severity of SARS-CoV-2 infection in Chinese patients remains unclear.

We retrospectively collected information from 829 patients infected with SARS-CoV-2 in Ningbo Medical Center Lihuili Hospital from December 05, 2022 to March 31, 2023, then divided them into four groups based on the severity of pneumonia. Last, we compared the difference in the number of shots of COVID-19 vaccine between the four groups, considering potential confounding factors using univariate and multivariate logistic regression.

Vaccination with two and three doses was positively associated with low prevalence of pneumonia and severe pneumonia both in crude and optimal models, while only three doses of the vaccine was correlated with low prevalence of death in SARS-CoV-2-infected patients. In optimal models, male SARS-CoV-2-infected individuals with advanced age were positively associated with high prevalence of pneumonia, severe pneumonia, and death; comorbidity with hypertension (OR = 2.532, p < 0.001) was positively associated with high prevalence of pneumonia (OR = 2.532, p < 0.001); and comorbidity with diabetes was positively associated with high prevalence of death (OR = 1.856, p = 0.011). However, this is a cross-sectional study and the causal relationships need to be further studied.

One dose of vaccine may not have a protective effect against pneumonia, severe pneumonia, and death; more than one dose of vaccine is an independent protective factor for pneumonia and severe pneumonia; and three doses of vaccine is an independent protective factor for death.

This study aims at evaluating the trend of glycemic control metrics during the infection of SARS-CoV-2 in individuals with Type 1 Diabetes (T1D) using a Continuous Glucose Monitoring (CGM) system and vaccinated against COVID-19.

This is a retrospective study of T1D subjects who got a breakthrough SARS-CoV-2 infection between November 2021 and February 2022. Data of glycemic control of CGM-derived metrics were compared 14 days before COVID-19 (Time 1), 14 days during COVID-19 (Time 2) and 14 days after COVID-19 (Time 3).

A total of 106 patients with T1D and breakthrough SARS-CoV-2 infection was included in the analysis. A significant reduction of GMI [%, 7.41 ± 1.60 vs 7.52 ± 1.63, P = 0.006)] and increase of TIR [%, 54.6 ± 20.4 vs 52.1 ± 19.7, P = 0.026] were observed at Time 3 as compared with Time 2. There was a significant reduction of SD (P < 0.001) and CV (P < 0.001) at Time 3 and Time 2 as compared with Time 1, associated with significant changes of mean glucose levels, TBR level 1 and total daily insulin doses.

Breakthrough SARS-CoV-2 infection did not worsen glycemic control in vaccinated people with T1D.

Three years into the coronavirus disease (COVID)-19 pandemic and the world is still struggling with the aftermath of this global health crisis. In Brazil, we are witnessing serious economic, health, social, and political problems. The rapid spread of the virus in our country was the result of a shortage of vaccines and the lack of an effective national campaign to identify and report cases. This health crisis also intensified social inequalities, hitting Indigenous peoples hard due to the lack of access to health services. In addition, rising unemployment and overcrowding of the health system made contagion possible, especially among the most vulnerable, increasing the number of serious cases of the disease. It is important to highlight that emotional problems worsened, the educational system was severely affected, and domestic violence increased during the confinement period, in addition to the fact that the pandemic exposed the great disparities of regional inequalities that exist across the country, mainly concerning health management.

Cytokines, notably interleukin-6 (IL-6), increase considerably in patients with severe corona virus disease 2019 (COVID-19). This vigorous immune response may cause end-organ failure or death; hence, measuring IL-6 in the context of patient characteristics may help predict outcomes and encourage early comprehensive therapy. This study investigated the association between serum IL-6 levels, COVID-19 severity, and demographic, clinical, and biochemical characteristics. COVID-19 inpatients in NMC hospitals were investigated between November 2020 and November 2021. Several patient variables related to serum IL-6 and COVID-19 severity have been examined. The study included 374 COVID-19 inpatients, 235 of whom had severe disease with a median age of 51. The elderly had an increased risk of severe COVID-19 (73.8%) compared with young adults (71%), with higher white blood cells, D-dimer, Lactate dehydrogenase, creatinine, ferritin, prothrombin time, Procalcitonin, and fibrinogen levels (P < .001). C-reactive protein, troponin, intensive care unit admission, disease severity score, and mortality were significantly associated with higher serum IL-6 levels (P = .05) in the univariate analysis, but this significance disappeared in the multivariate analysis. IL-6, along with other demographic and clinical variables affected COVID-19 severity. These characteristics may predict patients at risk of severe disease and assist in establishing early comprehensive disease outcome strategies. Large-scale clinical research is needed to emphasize IL-6 and COVID-19.

The COVID-19 pandemic has raised some concerns regarding the management of chronic skin diseases, especially in patients on immunosuppressive therapy including patients with pemphigus vulgaris (PV). Literature review reveals conflicting results about the effect of monoclonal antibodies such as rituximab on clinical outcome of COVID-19.

To assess the reciprocal interaction of COVID-19 and pemphigus and the effect of rituximab on prognosis of COVID-19 in patients.

We set up a retrospective study on adult patients with a confirmed diagnosis of pemphigus vulgaris and a history of COVID-19 with or without symptoms during 2020.

Thirty-six adults with pemphigus vulgaris and SARS-CoV-2 infection were included. The SARS-CoV-2 infection was confirmed with positive RT-PCR test results in 31 cases (86.1%) and suspected in the 5 others (13.9%). Gender, total dose of rituximab, number of rituximab cycles, and involvement of head and neck were not associated to duration of COVID-19 symptoms (p values: 0.32, 0.23, 0.84, and 0.51, respectively), severity of disease (hospitalization) (p values: 0.46, 0.39, 0.23, and 0.72, respectively), or the percentage of lung involvement on CT scan (p values: 0.07, 0.36, 0.38, and 0.09, respectively). Regarding the impact of COVID-19 on pemphigus, the majority of patients did not experience any changes in their pemphigus regarding clinical phenotype (100%) or severity (83.3%), but PV was worsened in 6 (16.9%) patients which was controlled with increasing the prednisolone dosage.

Rituximab appears to be safe with no increased risk of severe form of COVID-19 in patients with pemphigus vulgaris.

Anosmia, a total or partial loss of the ability to smell, is one of the most frequently documented sequelae of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Persistent anosmia is associated with a decrease in quality of life. Here, we assess the impact of virus lineage and vaccination status on anosmia development in the golden Syrian hamster model. To characterize anosmia driven by current variants, we assessed olfactory function in hamsters infected with SARS-CoV-2 lineages A, BA.2, BA.5, BQ.1, and BQ.1.1 using a buried food detection test. We found that significant anosmia occurs upon infection with all variants with a significant correlation between disease severity and degree of anosmia. Moreover, we found that vaccination with either the Pfizer (BNT16b2) or Moderna (mRNA-1273) mRNA vaccines does not protect against anosmia, despite protection against severe disease.

The clinical presentation of coronavirus disease 2019 (COVID-19) can vary widely, and while the primary infection involves the respiratory system, other organs can also be affected. This study presents the clinical and epidemiological characteristics of hospitalized COVID-19 patients in a tertiary hospital in Ado Ekiti, South-West Nigeria.

This is a retrospective study involving COVID-19 patients admitted to the isolation ward between August 2020 and January 2021. The data used for this study was obtained from the patient's medical record, which includes demographic characteristics, clinical presentation, baseline co-morbidities, and laboratory investigations.

The average age of the patients was 60.3 years, and more than two-thirds were male. The most common symptoms were fever, shortness of breath, cough, and tiredness. Comorbidities identified among the patients included diabetes mellitus, heart disease, obesity, and chronic kidney disease. The most common radiological findings were bilateral homogeneous patchy opacities and peripheral fluffy infiltrates. The overall mortality rate was 21.9%, with 13 deaths in patients with severe disease. Age and duration of admission were found to be significant predictors of death.

The results of this study provide valuable insights into the clinical presentation of COVID-19 in Nigeria and may guide future management strategies for similar infections.

The impact of multiple risk factors on COVID-19 mortality has been previously reported in multiple systematic reviews and meta-analyses. The aim of this review is to provide a comprehensive update on the association between hypertension (HTN) and mortality in patients with COVID-19.

A systematic review and meta-analysis were performed and followed the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. A search was achieved using PubMed, Scopus, and Cochrane Databases for research publications on hypertension, COVID-19, and mortality published between December 2019 and August 2022.

A total of 23 observational studies involving 611,522 patients from 5 countries (China, Korea, the UK, Australia, and the USA) were included in our study. The confirmed number of COVID-19 with HTN cases in each study ranged from 5 to 9964. The mortality ranged from 0.17% to 31% in different studies. Pooled results show that the mortality rate of COVID-19 among the included studies ranges from a minimum of 0.39 (95% CI 0.13-1.12) to a maximum of 5.74 (95% CI 3.77-8.74). Out of the 611,522 patients, 3119 died which resulted in an overall mortality prevalence of 0.5%. Subgroup analyses indicated that patients with COVID-19 who have hypertension and male patients had slightly less risk of mortality than female patients [the percentage of men > 50%; OR 1.33: 95% CI (1.01, 1.76); the percentage of men ≤ 50%: OR 2.26; and 95% CI (1.15, 4.48)]. Meta-regression analysis results also showed a statistically significant association between hypertension and COVID-19 mortality.

This systematic review and meta-analysis suggest that hypertension may not be the only risk factor associated with the increased mortality rate during the COVID-19 pandemic. In addition, a combination of other comorbidities and old age appears to increase the risk of mortality from COVID-19. The impact of hypertension on mortality rate among COVID-19 patients.

The GENCOV study aims to identify patient factors which affect COVID-19 severity and outcomes. Here, we aimed to evaluate patient characteristics, acute symptoms and their persistence, and associations with hospitalization. Participants were recruited at hospital sites across the Greater Toronto Area in Ontario, Canada. Patient-reported demographics, medical history, and COVID-19 symptoms and complications were collected through an intake survey. Regression analyses were performed to identify associations with outcomes including hospitalization and COVID-19 symptoms. In total, 966 responses were obtained from 1106 eligible participants (87% response rate) between November 2020 and May 2022. Increasing continuous age (aOR: 1.05 [95%CI: 1.01-1.08]) and BMI (aOR: 1.17 [95%CI: 1.10-1.24]), non-White/European ethnicity (aOR: 2.72 [95%CI: 1.22-6.05]), hypertension (aOR: 2.78 [95%CI: 1.22-6.34]), and infection by viral variants (aOR: 5.43 [95%CI: 1.45-20.34]) were identified as risk factors for hospitalization. Several symptoms including shortness of breath and fever were found to be more common among inpatients and tended to persist for longer durations following acute illness. Sex, age, ethnicity, BMI, vaccination status, viral strain, and underlying health conditions were associated with developing and having persistent symptoms. By improving our understanding of risk factors for severe COVID-19, our findings may guide COVID-19 patient management strategies by enabling more efficient clinical decision making.

Devastating consequences of COVID-19 disease enhanced the role of promoting prevention-focused practices. Among targeted efforts, diet is regarded as one of the potential factors which can affect immune function and optimal nutrition is postulated as the method of augmentation of people's viral resistance. As epidemiological evidence is scarce, the present study aimed to explore the association between dietary intake of total polyphenols, lignans and plant sterols and the abundance of immunomodulatory gut microbiota such as Enterococcus spp. and Escherichia coli and the risk of developing COVID-19 disease.

Demographic data, dietary habits, physical activity as well as the composition of body and gut microbiota were analyzed in a sample of 95 young healthy individuals. Dietary polyphenol, lignan and plant sterol intakes have been retrieved based on the amount of food consumed by the participants, the phytochemical content was assessed in laboratory analysis and using available databases.

For all investigated polyphenols and phytosterols, except campesterol, every unit increase in the tertile of intake category was associated with a decrease in the odds of contracting COVID-19. The risk reduction ranged from several dozen percent to 70 %, depending on the individual plant-based chemical, and after controlling for basic covariates it was statistically significant for secoisolariciresinol (OR = 0.28, 95% CI: 0.11-0.61), total phytosterols (OR = 0.47, 95% CI: 0.22-0.95) and for stigmasterols (OR = 0.34, 95% CI: 0.14-0.72). We found an inverse association between increased β-sitosterol intake and phytosterols in total and the occurrence of Escherichia coli in stool samples outside reference values, with 72% (OR = 0.28, 95% CI: 0.08-0.86) and 66% (OR = 0.34, 95% CI: 0.10-1.08) reduced odds of abnormal level of bacteria for the highest compared with the lowest tertile of phytochemical consumption. Additionally, there was a trend of more frequent presence of Enterococcus spp. at relevant level in people with a higher intake of lariciresinol.

The beneficial effects of polyphenols and phytosterols should be emphasized and these plant-based compounds should be regarded in the context of their utility as antiviral agents preventing influenza-type infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 19 (COVID-19), has caused a global health crisis. Despite ongoing efforts to treat patients, there is no universal prevention or cure available. One of the feasible approaches will be identifying the key genes from SARS-CoV-2-infected cells. SARS-CoV-2-infected in vitro model, allows easy control of the experimental conditions, obtaining reproducible results, and monitoring of infection progression. Currently, accumulating RNA-seq data from SARS-CoV-2 in vitro models urgently needs systematic translation and interpretation. To fill this gap, we built COVIDanno, COVID-19 annotation in humans, available at http://biomedbdc.wchscu.cn/COVIDanno/. The aim of this resource is to provide a reference resource of intensive functional annotations of differentially expressed genes (DEGs) among different time points of COVID-19 infection in human in vitro models. To do this, we performed differential expression analysis for 136 individual datasets across 13 tissue types. In total, we identified 4,935 DEGs. We performed multiple bioinformatics/computational biology studies for these DEGs. Furthermore, we developed a novel tool to help users predict the status of SARS-CoV-2 infection for a given sample. COVIDanno will be a valuable resource for identifying SARS-CoV-2-related genes and understanding their potential functional roles in different time points and multiple tissue types.

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.

The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause of death and potentially contributed to a decline in life expectancy in the United States. The severe acute respiratory syndrome-related coronavirus-2 binds to the surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) leading to tissue infection and viral replication. ACE2 is an important enzymatic component of the renin-angiotensin system (RAS) expressed in the lung and other organs. The peptidase regulates the levels of the peptide hormones Ang II and Ang-(1-7), which have distinct and opposing actions to one another, as well as other cardiovascular peptides. A potential consequence of severe acute respiratory syndrome-related coronavirus-2 infection is reduced ACE2 activity by internalization of the viral-ACE2 complex and subsequent activation of the RAS (higher ratio of Ang II:Ang-[1-7]) that may exacerbate the acute inflammatory events in COVID-19 patients and possibly contribute to the effects of long COVID-19. Moreover, COVID-19 patients present with an array of autoantibodies to various components of the RAS including the peptide Ang II, the enzyme ACE2, and the AT1 AT2 and Mas receptors. Greater disease severity is also evident in male COVID-19 patients, which may reflect underlying sex differences in the regulation of the 2 distinct functional arms of the RAS. The current review provides a critical evaluation of the evidence for an activated RAS in COVID-19 subjects and whether this system contributes to the greater severity of severe acute respiratory syndrome-related coronavirus-2 infection in males as compared with females.