Severe COVID-19 Research Articles

Cardiopulmonary long-term effects 6, 18 and 30 months after severe COVID-19 infection

Abstract Background SARS-CoV-2 infection affects the cardiopulmonary system in both the acute and long-term phase. This study aimed to comprehensively assess symptoms and potential longterm impairments 6, 18 and 30 months in patients previously hospitalized for severe Covid-19 infection. Methods This prospective registry included patients hospitalized for PCR-confirmed Covid-19 infection. Approximately 6 months post-discharge, follow-up examination included patient history, clinical examination, echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a comprehensive laboratory panel. Patients with pathologic findings during the first visit underwent a second (at 18 months) and third (at 30 months) follow-up examination. Those without pathologic findings or who refused further medical examinations were contacted via phone to inquire about symptoms. Results Between July 2020 and April 2022, 200 patients (91% general ward, 9% intensive care unit) were recruited. Due to dropouts, the second visit was conducted in 170 patients and the third visit in 139 (74 in person, 65 via telephone). Long Covid criteria were fulfilled by 73% at 6 months, 52% at 18 months and 49% at 30 months post-discharge, with fatigue being the most common symptom (Figure 1). Echocardiography at 6 months showed impaired left ventricular function in 15 patients, with normalization in 80% at 18 months and further 66% at 30 months (Figure 2). cMRI revealed pericardial effusions in 28 patients at 6 months, which resolved in 47% at 18 months and in further 60% at 30 months. Signs of peri- or myocarditis were present in 7 patients at 6 months and were resolved in all 4 patients who attended control studies at 18 months. PFT at 6 months detected reduced vital capacity in 17 patients, of whom 10% returned to normal at 18 months and a further 66% showed normalization at 30 months. Chest CT scans at 6 months identified post-infectious residues in 41 patients, with full recovery in 20% at 18 months without further normalization after 30 months. The length of in-hospital stay was identified as a significant predictor for persisting Long Covid 6 months after discharge (95% CI: 1.005 - 1.12, p=0.03). No predictors have been found for Long Covid at 18 and 30 months. Conclusion While the prevalence of Long Covid decreased over time, a significant symptom burden persisted at 6, 18 and even 30 months after severe Covid-19 infection. Structural and functional abnormalities were less frequent compared to reported symptoms, posing a challenge in substantiating the causes of these symptoms.

Impact of primary course COVID-19 vaccination on hospitalizations in Belgium, a Bayesian approach

Abstract Background The Belgian COVID-19 primary course vaccine rollout was prioritized for individuals aged 18-64 years with underlying health conditions (increased risk of severe COVID-19), over their peers of the same age. This led to a 32-day earlier vaccination of prioritized individuals. In this research, we assessed the impact of vaccine rollout prioritization on hospitalizations for COVID-19 in Belgium between April 1st 2021 and June 30th 2021. Methods The sample consisted of the Belgian population aged 18-64 years. Individuals were classified by their priority status according to underlying health conditions and by vaccination status, creating weekly changing cohorts. The hospitalization probability was estimated by cohort using a national COVID-19 hospital surveillance. Two counterfactual scenarios were considered: (1) a no vaccination scenario and (2) a scenario in which the vaccine administration occurred at random in both cohorts (a vaccine rollout without prioritization). We used a Bayesian model to jointly estimate cohort-specific hospitalization probability and scenario outcomes. Results Out of the sample of 5,448,534 individuals, 22.65 % was prioritized. By May 1st, vaccination coverage was 18% and 2% within the prioritized and the non-prioritized cohort. In scenario 2, coverage within the prioritized was 6% by May 1st. There were 6968 hospitalizations reported through the hospital survey. Our initial scenario-outcomes indicated a reduction in hospitalizations of 3203 (95%CI[2548;3858]) and 919 (95%CI[406;1433]) by the vaccination prioritization, compared to scenarios 1 and 2, respectively. Conclusions This research provides insights in the impact of vaccination in a pandemic context in Belgium. We report a significant reduction in simulated COVID-19 hospitalization by vaccine prioritization compared to at random vaccination and no vaccination at all. Currently, we are investigating the effect of age-dependent vaccination next to at random vaccination. Key messages • The prioritised vaccination campaign in Belgium led to a significant reduction in hospitalizations. • Prioritisation based on underlying health conditions is an important public health measure.

Mortality related to different circulatory diseases: a multiple causes of death analysis, 2008-2022

Abstract Background Mortality from circulatory diseases significantly increased in 2020 compared to pre-pandemic years in many countries. However, data were mostly limited to the underlying cause of death and to the first phases of the pandemic. Analyses of any mention of a disease in death certificates (multiple causes of death approach, MCOD) are more robust to changes in coding rules/practices and to the role of COVID-19 as a competing cause of death. Methods Mortality records were extracted from 2008 to 2022 among residents of the Veneto Region (Northeastern Italy, 4.9 million population). Based on MCOD, age-standardized mortality rates (2013 European standard) were computed for ischemic heart diseases (IHD), cerebrovascular diseases (CVD), atrial fibrillation (AF), and hypertensive diseases (HD). The annual percent change (APC) was estimated through the pre-pandemic period (2008-2019), and change in rates during pandemic years were computed compared to 2019. Results Before the pandemic, rates were steeply declining for IHD (APC -5.1%; 95%CI -5.5, -4.6) and CVD (-4.0%; -4.4, -3.5); mortality related to HD reduced at a slower pace (-1.9%; -2.3, -1.4), whereas AF-related mortality was increasing (+1.0%; 0.1, 1.8). During the first year of the pandemic, the growth in mortality compared to 2019 was +26% for HD, +18% for AF, +13% for CVD and +12% for IHD. In 2021-2022, rates for CVD and IHD returned to pre-pandemic levels; rates for HD reduced with respect to 2020 but remained above the baseline; AF-related mortality was still increasing. Conclusions The pandemic differentially impacted mortality associated to different circulatory diseases, depending on pre-existing long-term trends (increasing for AF) and on susceptibility to severe COVID-19 disease (higher for HD). Continuous surveillance based on MCOD is warranted to properly assess changes in mortality associated to specific circulatory diseases after the end of the pandemic. Key messages • Multiple causes of death analyses are warranted to assess how the pandemic affected pre-existing long term trends in cause-specific mortality. • Mortality related to different circulatory diseases increased in 2020, but pre-pandemic trends, the extent of the increase in 2020, and further changes observed in 2021-2022 largely diverged.

SARS-CoV-2 Infection And COVID-19 Outcomes Among Mental Disorders: A Register-based Study in Catalonia

Abstract This study aimed to study the risk of SARS-CoV-2 infection and severe COVID-19 outcomes across different mental diagnoses and to assess the role of sex in these associations. We used electronic health records from Catalonia to identify adults receiving inpatient/outpatient mental health care between 2017-2019 with diagnosis of non-affective psychosis (NAP), bipolar disorder (BD), depressive disorder (DEP), stress-related disorders, neurotic/somatoform disorders (NSD), and substance misuse (SUB) (exposed). Outcomes included SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19-related death. Adjusted logistic regression analyses were conducted. 785,378 adults were included (70.3% < 65 years old; 57.1% women). Compared to unexposed, those with NAP [OR (95%CI): 0.84 (0.80-0.88)], BD [0.80 (0.75-0.86)], DEP [0.97 (0.94-1.00)] and SUB [0.81 (0.78-0.84)] had a lower risk of SARS-CoV-2 infection, while people with NSD presented an increased risk [1.03 (1.01-1.06)]. Among those infected, people with DEP, NSD, and SUB had a lower risk of COVID-19 hospitalization, but higher risk of COVID-19-related death [1.23 (1.07-1.41); 1.26 (1.07-1.48); 1.48 (1.24-1.71), respectively]. A higher COVID-19-related death was also found in people with NAP and BD [1.68 (1.34-2.12); 2.02 (1.50-2.73)]. Sex-stratified analysis showed that women with NSD were especially vulnerable to infection [1.07 (1.03-1.11)], and women with DEP and NSD to COVID-19-related death [1.24 (1.05-1.47); 1.26 (1.02-1.54)]. These results suggest different vulnerabilities to infection and COVID-19 hospitalization and death across mental disorders. These findings have implications for pandemic preparedness, highlighting the need for specific public health strategies to mitigate the excess of mortality of people with certain mental disorders.

Difference in long COVID prevalence due to different definitions and long COVID related risk factors

Abstract Several definitions of long COVID are used in research and practice what challenges epidemiological investigations. Here we present differences in long COVID prevalence accounting for several definitions and concordance between the definitions, as well as the risk factors associated with long COVID. Definitions considered were WHO post-COVID19 condition (PCC) definition with several thresholds (at least low - standard definition, moderate or strong impact on daily activities), NICE1 and NICE2 definitions (reported at least one or at least two symptoms), United States National Centre for Health Statistics, and United Kingdom Office for National Statistics definitions and perceived long COVID. Prevalence of long COVID among French adult population (N = 10 615) in autumn 2022 ranged from 1.2% to 13.4%, conditional of the definition. The concordance between the definitions was at best moderate. Next, on a smaller representative sample of a French adult population (N = 1 813) eight potential risk factors groups for long COVID were assessed in a systematic epidemiological investigation, following a conceptual model. Fifteen factors from seven groups were associated with long COVID including early-defined sociodemographic characteristics, pre-existing chronic conditions, short-term work-related factors, current socioeconomic position, health behaviours, infection-related factors, and perception of COVID-19 severity and long COVID. The likelihood of long COVID was higher for individuals with higher number of diseases and for nineteen out of twenty-six most prevalent dyads and a triad. A more standardized definition would facilitate research and surveillance of long COVID. Furthermore, long COVID should be observed as an interplay of social, medical and contextual factors rather than a mere complication of SARS-COV-2 infection, while patients with multimorbidity may present some of the particularly vulnerable population groups.

The Impact of COVID-19 Vaccination and Infection on the Exacerbation of Myasthenia Gravis

Objectives: Myasthenia Gravis (MG) is an autoimmune disorder that can exacerbate for various reasons, including vaccination and infection. This study aimed to investigate the safety of COVID-19 vaccines for MG patients, factors influencing MG exacerbation after COVID-19 infection (MECI), the course and prognosis of MECI, and the impact of COVID-19 vaccine on infected MG patients. Methods: Patients were enrolled from the MG database in the Department of Neurology, Xuanwu Hospital, Capital Medical University. Two questionnaires were administered to collect data concerning COVID-19 vaccination (questionnaire 1, Q1) and infection (questionnaire 2, Q2) during two distinct periods. MG exacerbation was defined as an increase of at least two points in the MG activity of daily living (MG-ADL) score. COVID-19 severity was categorized as “hospitalization” or “home management”; Results: During the first data-collecting period, our database registered 1013 adult patients: 273 (26.9%) had received COVID-19 vaccinations and completed Q1, and 8 (2.9%) experienced MG exacerbation after vaccination. During the second data-collecting period, among the newly registered patients, 366 patients completed Q2. Of these, 244 were infected, with 39 (16.0%) experiencing MECI and 21 (8.6%) requiring hospitalization. Multivariate analysis showed that generalized myasthenia gravis was associated with MECI (OR 3.354, 95% CI: 1.423–7.908, p = 0.006). Among the 244 infected patients, 143 had received COVID-19 vaccinations, including 14 who received their booster dose within 6 months before COVID-19 and 129 who were vaccinated more than 6 months before COVID-19. The remaining 101 were unvaccinated. No significant associations were found between COVID-19 vaccination and COVID-19 severity (p = 0.292) or MECI incidence (p = 0.478); Conclusions: COVID-19 vaccines were found to be safe for MG patients in stable condition. Patients with gMG were more susceptible to experiencing MECI. No significant impact of the vaccine on COVID-19 severity or MECI incidence was observed.

The silent predictors: exploring galectin-3 and Irisin’s tale in severe COVID-19

ObjectiveThis study aimed to evaluate the roles of galectin-3 and irisin as biomarkers in predicting severe outcomes in COVID-19 patients.ResultsWe analyzed serum levels of galectin-3 and irisin in 59 patients with severe COVID-19 and 30 healthy controls. Elevated galectin-3 levels were associated with increased risks of mortality, need for intensive care, and severe acute respiratory distress syndrome. The optimal cut-off value for galectin-3 was 13.47 ng/ml, with a sensitivity of 72.7% and specificity of 76.6%. Irisin levels did not differ significantly between survivors and non-survivors at admission or on the 3rd day post-admission, but approached significance on the 7th day. These findings suggest that galectin-3 could be a valuable prognostic biomarker for severe COVID-19 outcomes, while irisin’s role remains to be clarified in further studies.

Lecturer

COVID-19 is a highly contagious viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It primarily affects the respiratory system but can also impact other significant organs. Its rapid spread has heightened interest in biomarkers for screening and early diagnosis. This study evaluated D-dimer, C-reactive protein (CRP), and complete blood count (CBC) levels in patients with COVID-19 compared to healthy individuals. A total of 50 healthy individuals and 50 COVID-19 patients, aged 20 to 65, were included in the study, excluding individuals with conditions such as leukemia, thalassemia, or pregnancy. Whole blood and plasma samples were collected for CBC and D-dimer assays and stored at 2-4°C. The COVID-19 patients had significantly higher levels of D-dimer, CRP, white blood cells (WBC), granulocytes, and granulocyte percentage as compared with the healthy individuals (p<0.01), lower levels of lymphocyte percentage, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) (p<0.01), as shown. The severe COVID-19 cases often show elevated D-dimer levels, indicating a higher risk of thrombosis. Increased CRP levels correlate with more severe conditions and help assess inflammation severity. A CBC provides insights into blood components, like RBC and WBC, and platelets. During COVID-19, CBC results may reveal lymphopenia, a low lymphocyte count linked to increased severity. For the most accurate and current information, consult healthcare professionals, reliable health organizations, or recent scientific studies on COVID-19.

Chemokine CCL2 and its receptor CCR2 in different age groups of patients with COVID-19

BackgroundDespite the development of various antiviral drugs, most of them are not effective in the treatment of coronavirus disease 2019 (COVID-19) as a hyperinflammatory disorder. Chemokine (C-C motif) ligand 2 (CCL2) is one of the critical CC chemokines involved in the pathogenesis and severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This study aimed to investigate the expression of CCL2 and CC chemokine receptor 2 (CCR2) in COVID-19 patients.MethodsPeripheral blood samples were collected from 60 confirmed COVID-19 patients and 60 age-matched healthy subjects. The ages of the subjects were categorized as follows: up to 20 years, 20 to 40 years, 40 to 60 years, and more than 60 years. CCL2 serum levels were measured using the enzyme-linked immunosorbent assay (ELISA). CCR2 gene expression in peripheral blood mononuclear cells (PBMCs) was measured employing real-time polymerase chain reaction (PCR).ResultsIn all age groups, CCL2 serum levels were significantly elevated in patients compared to healthy controls (P < 0.0001). CCL2 levels were higher in severe patients than in moderate patients. Moreover, CCR2 expression by PBMCs was higher in patients compared to control subjects. However, a significant difference between patients and controls over 60 years of age was identified (P = 0.0353). There was no significant difference in CCR2 expression between moderate and severe COVID-19 patients.ConclusionsTaken together, the findings demonstrate that CCL2 and CCR2 are upregulated in COVID-19 patients at protein and mRNA levels, respectively. Therefore, the CCL2/CCR2 axis may be a potential therapeutic target in order to improve patient outcomes.

Profiling the transcriptomic age of single-cells in humans

Although aging clocks predicting the age of individual organisms have been extensively studied, the age of individual cells remained largely unexplored. Most recently single-cell omics clocks were developed for the mouse, however, extensive profiling the age of human cells is still lacking. To fill this gap, here we use available scRNA-seq data of 1,058,909 blood cells of 508 healthy, human donors (between 19 and 75 years), for developing single-cell transcriptomic clocks and predicting the age of human blood cells. By the application of the proposed cell-type-specific single-cell clocks, our main observations are that (i) transcriptomic age is associated with cellular senescence; (ii) the transcriptomic age of classical monocytes as well as naive B and T cells is decreased in moderate COVID-19 followed by an increase for some cell types in severe COVID-19; and (iii) the human embryo cells transcriptomically rejuvenated at the morulae and blastocyst stages. In summary, here we demonstrate that single-cell transcriptomic clocks are useful tools to investigate aging and rejuvenation at the single-cell level.

HbA1c and leukocyte mtDNA levels as major factors associated with post-COVID-19 syndrome in type 2 diabetes patients

Post-COVID-19 syndrome (PCS) is an emerging health problem in people recovering from COVID-19 infection within the past 3–6 months. The current study aimed to define the predictive factors of PCS development by assessing the mitochondrial DNA (mtDNA) levels in blood leukocytes, inflammatory markers and HbA1c in type 2 diabetes patients (T2D) with regard to clinical phenotype, gender, and biological age. In this case-control study, 65 T2D patients were selected. Patients were divided into 2 groups depending on PCS presence: the PCS group (n = 44) and patients who did not develop PCS (n = 21) for up to 6 months after COVID-19 infection. HbA1c and mtDNA levels were the primary factors linked to PCS in different models. We observed significantly lower mtDNA content in T2D patients with PCS compared to those without PCS (1.26 ± 0.25 vs. 1.44 ± 0.24; p = 0.011). In gender-specific and age-related analyses, the mt-DNA amount did not differ significantly between the subgroups. According to the stepwise multivariate logistic regression analysis, low mtDNA content and HbA1c were independent variables associated with PCS development, regardless of oxygen, glucocorticoid therapy and COVID-19 severity. The top-performing model for PCS prediction was the gradient boosting machine (GBM). HbA1c and mtDNA had a notably greater influence than the other variables, indicating their potential as prognostic biomarkers.

Clinical implications of persistently increased blood urea nitrogen/serum creatinine ratio (PI-BUN/Cr) in severe COVID-19 patients

BackgroundPatients with COVID-19 may experience a persistent increase in the blood urea nitrogen over creatinine ratio (PI-BUN/Cr). Its elevation could reflect multiple underlying pathophysiological processes beyond prerenal injury but also warrants nuanced interpretation due to its complex interplay with various factors, underscoring the importance of investigating its effects on mortality and acute kidney injury in this population.MethodsWe analized a retrospective and longitudinal cohort of patients admitted to a single center in Mexico City for patients with severe COVID-19. Between March 5, 2020 and August 25, 2021, we included patients with confirmed positive diagnosis for SARS-CoV-2, age > 18 years, disease severity was defined by clinical data of respiratory distress syndrome and a ratio of partial oxygen pressure to inspired oxygen fraction < 300 mmHg on admission. We excluded patients with End Stage Kidney Disease. Data was obtained from electronic medical records. PI-BUN/Cr was defined as an increase in the BUN/Cr ratio > 30 in more than 60% of measurements in the hospital. The outcomes included: risk factors to mortality and AKI in-hospital.ResultsThe cohort included 3,007 patients with a median age of 54.6 ± 14.5 years. 35% of patients died; 44.6% developed PI-BUN/Cr ratio and 71.4% AKI. Mortality was associated with older age > 60 years [Hazard ratio (HR)] = 1.45, 95% CI: 1.28–1.65; p < 0.001); male (HR 1.25, 95% CI 1.09–1.44; p = 0.002) and AKI (HR 3.29, 95% CI 2.42–4.46; p < 0.001); PI-BUN/CR & Non-AKI (HR = 2.82, 95% CI: 1.61–4.93; p < 0.001); Non PI-BUN/CR & AKI (HR = 5.47, 95% CI: 3.54–8.44; p < 0.001); and PI-BUN/CR & AKI (HR = 4.26, 95% CI: 2.75–6.62, p < 0.001). Only hiperuricemia was a risk factor for AKI (HR = 1.71, 95% CI: 1.30–2.25, p < 0.001).ConclusionsWhile PI-BUN/Cr alone may not directly associate with mortality, its capacity to sub-phenotype patients according to their AKI status holds significant promise in offering valuable insights into patient prognosis and outcomes. Understanding the nuanced relationship between PI-BUN/Cr and AKI enhances our comprehension of renal function dynamics. It equips healthcare providers with a refined tool for risk stratification and personalized patient management strategies.

Association Between the Use of Proton Pump Inhibitors and Severe Clinical Outcomes in COVID-19 Patients: A Retrospective Observational Study.

Background Proton pump inhibitors (PPIs) increase the risk of pneumonia secondary to PPI-induced hypochlorhydria. We aim to investigate the association between PPI and disease severity in coronavirus disease 2019 (COVID-19)-positive patients and the risk of hospitalizations in Muscat, Oman. Methodology COVID-19-positive patients aged 18 years and above at the time of diagnosis were included in this retrospective observational study. The details of the patients were retrieved from the electronic health records of the Al Shifa Hospital Information Management System and Tarassud. The composite primary endpoint was COVID-19 admission to a government tertiary hospital ward or intensive care within 14 days of diagnosis. Results A total of 506 COVID-19-positive patients were identified during the specified period. The mean age was 44 ± 15 years. The majority of the patients were Omani, and a female preponderance was observed. Overall, 104 (20.4%) patients were current PPI users. Admission due to COVID-19 was significantly associated with the presence of comorbid conditions such as diabetes mellitus (p = 0.001), hypertension (p = 0.001), and chronic kidney disease (p < 0.001). However, current PPI use (p = 0.140) was not significantly associated with an increased risk of hospitalization. Conclusions This data suggests that the use of PPIs during COVID-19 infection did not increase the risk of severe COVID-19 infection and poor outcomes leading to hospitalization in Muscat, Oman. However, the presence of other medical comorbidities, such as diabetes and hypertension, was associated with a higher risk of adverse clinical symptoms that resulted in hospitalization.

Mexican Hispanics show significant improvement in lung function approximately 1year after having severe COVID-19.

The long-term effects of COVID-19 on lung function are not understood, especially for periods extending beyond 1year after infection. This observational, longitudinal study investigated lung function in Mexican Hispanics who experienced severe COVID-19, focusing on how the length of recovery affects lung function improvements. At a specialized COVID-19 follow-up clinic in Yucatan, Mexico, lung function and symptoms were assessed in patients who had recovered from severe COVID-19. We used z-scores, and Wilcoxon's signed rank test to analyse changes in lung function over time. Lung function was measured twice in 82 patients: the first and second measurements were taken a median of 94 and 362days after COVID-19 diagnosis, respectively. Initially, 61% of patients exhibited at least one of several pulmonary function abnormalities (lower limit of normal = -1.645), which decreased to 22% of patients by 390days post-recovery. Considering day-to-day variability in lung function, 68% of patients showed improvement by the final visit, while 30% had unchanged lung function from the initial assessment. Computed tomography (CT) scans revealed ground-glass opacities in 33% of patients. One year after infection, diffusing capacity of the lungs for carbon monoxide z-scores accounted for 30% of the variation in CT fibrosis scores. There was no significant correlation between the length of recovery and improvement in lung function based on z-scores. In conclusion, 22% of patients who recovered from severe COVID-19 continued to show at least one lung function abnormality 1year after recovery, indicating a prolonged impact of COVID-19 on lung health.

Aromatase, testosterone, TMPRSS2: determinants of COVID-19 severity

BackgroundMale sex has been identified as a risk factor for worse COVID-19 outcomes. This sex difference has been mostly attributed to the complex role of sex hormones. Cell surface entry of SARS-CoV-2 is mediated by the transmembrane protease serine 2 (TMPRSS2) which is under transcriptional regulation by androgens. P450 aromatase enzyme converts androgens to estrogens. This study measured concentrations of aromatase enzyme, testosterone, estradiol, and TMPRSS-2 in plasma of hospitalized COVID-19 patients to elucidate the dynamics of sex-linked disparity in COVID-19 and correlate them with disease severity and mortality.MethodsIn this prospective cohort study, a total of 265 patients (41% women), age 18 years and older, who had a positive COVID-19 PCR test and were hospitalized for COVID-19 at Memorial Hermann Hospital in Houston, (between May 2020 and May 2021) were enrolled in the study if met inclusion criteria. Plasma concentrations of Testosterone, aromatase, TMPRSS-2, and estradiol were measured by ELISA. COVID-19 patients were dichotomized based on disease severity into moderate-severe (n = 146) or critical (n = 119). Mann Whitney U and logistic regression were used to correlate the analytes with disease severity and mortality.ResultsTMPRSS2 (2.5 ± 0.31 vs. 1.73 ± 0.21 ng/mL, p < 0.01) and testosterone (1.2 ± 0.1 vs. 0.44 ± 0.12 ng/mL, p < 0.01) were significantly higher in men as compared to women with COVID-19 after adjusting for age in a multivariate model. There was no sex difference seen in the level of estradiol and aromatase in COVID-19 patients. TMPRSS2 and aromatase were higher, while testosterone was lower in patients with increased COVID-19 severity. They were independently associated with COVID-19 severity, after adjusting for several baseline risk factors in a multivariate logistic regression model. In terms of mortality, TMPRRS2 and aromatase levels were significantly higher in non-survivors.ConclusionsOur study demonstrates that testosterone, aromatase, and TMPRSS2 are markers of COVID-19 severity. Estradiol levels do not change with disease severity in COVID-19. In terms of mortality prediction, higher aromatase and TMPRSS-2 levels can be used to predict mortality from COVID-19 in hospitalized patients.Plain English SummaryCOVID-19 has caused over a million deaths in the U.S., with men often getting sicker than women. Testosterone, a male hormone, helps control a protein called TMPRSS-2, which allows the COVID-19 virus to spread more easily in the body. A protein called aromatase converts the male hormone testosterone into the female hormone estrogen. It is thought that female hormone estrogen helps protect women from getting seriously ill from COVID-19. To understand the role of these hormones in COVID-19 and sex differences, we measured levels of testosterone, estrogen, aromatase (which turns testosterone into estrogen), and TMPRSS-2 in hospitalized COVID-19 patients. We also checked how this level might reflect the severity of the disease. We found that critically ill COVID-19 patients (the ones in ICU) had higher levels of TMPRSS-2 and aromatase, and lower testosterone levels. When we used these hormone levels to predict death in hospitalized COVID-19 patients, higher levels of TMPRSS-2 and aromatase were linked to a lower chance of survival.

Distribution Of Microrna Counts Across Human Chromosomes.

microRNAs (miRNAs) are a class of non-coding RNAs that play important roles in gene regulation. miRNAs are transcribed from DNA sequences into primary miRNAs and then processed into precursor miRNAs and mature miRNAs. miRNA gene counts in chromosomes for different species have been studied. Certain chromosomes have higher numbers of miRNA genes in all species, such as the X chromosome, while the Y chromosome has the fewest or no miRNA genes. miRNA counts in different chromosomes might have a positive correlation with coding gene counts in many species. In this study, a regression model was used to find the relationship between the miRNA count and the coding gene count across human chromosomes, and miRNA counts for 23 human chromosomes were predicted based on this regression model. In addition, the chromosome locations for the miRNA biomarkers of major depression, diabetes, Parkinson's disease, and COVID-19 are discussed. The results reveal that miRNA biomarkers of these diseases are located in various chromosomes. The dispersion of miRNA locations across different chromosomes might explain the complication of the pathology of these diseases. Moreover, diabetes and COVID-19 have the largest number of miRNA biomarkers from Chromosome X. As Chromosome X is a sex chromosome, this phenomenon may explain the gender difference in the prevalence or severity of diabetes and COVID-19. The significant gender difference in the prevalence or severity of diabetes and COVID-19 might be due to the regulation function of their miRNA biomarkers from Chromosome X.

Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19

Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a few other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad spectrum of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers. In particular, CAST/EiJ, a wild-derived strain, developed high lung viral burdens, more severe lung pathology than seen in other CC strains, and a dysregulated cytokine profile resulting in morbidity and mortality. These inbred mouse strains may serve as a valuable platform to evaluate therapeutic countermeasures against severe COVID-19 and other coronavirus pandemics in the future.

The role of transforming growth factor-β in lung damage in COVID-19: clinical and diagnostic parallels

BACKGROUND: Coronavirus 2 (SARS-CoV-2), which causes severe acute respiratory syndrome in COVID-19, leads to complex immune reactions, hyperactivation of immunocompetent cells, including increased degranulation activity of mast cells and the release of their secretome products. The SARS-CoV-2 virus and the subsequent strong immune and inflammatory response, as well as a violation of the regulation of coagulation and fibrinolytic pathways, cause massive activation of latent TGF-β in the lungs, as well as the latent pool of TGF-β in the blood of patients with COVID-19. AIMS: To assume the participation of transforming growth factor-β (TGF-β) in lung damage in patients with COVID-19 by determining its quantitative level in autopsy lung samples in patients with COVID-19 and to conduct a correlation analysis with clinical and laboratory parameters. MATERIALS AND METHODS: The study included samples of lung autopsy material obtained from patients who died from severe COVID-19. A correlation analysis of TGF-β-positive cells and clinical and laboratory parameters was also performed. RESULTS: Extensive representation of TGF-β-positive cells was found in lung tissues of patients who died from COVID-19.A negative correlation was revealed: between TGF-β and the content of nucleated neutrophils in the blood (r = - 0,617; p = 0,033); between TGF-β and the level of C-reactive protein (CRP) according to the results of blood biochemistry (r = - 0,491; p = 0,013). A positive correlation was revealed between TGF-β and the content of blood platelets (r = 0,384; p =0,012);TGF-β with the level of erythrocyte sedimentation rate (ESR) (r = 0,409; p = 0,025). A positive correlation was also found between TGF-β and the presence of cough in the patient at the beginning of hospitalization (r = 0,367; p = 0,046). CONCLUSIONS: Activation of TGF-β in the lungs of patients who died from severe COVID-19 correlates with the level of neutrophils, platelets, ESR, CRP and the presence of cough in the patient. Further research is needed on the activation, release of TGF-β and its interactions in larger cohorts of patients. These correlations suggest the negative involvement of the transforming growth factor and consider the therapeutic possibilities of regulatory influence on its activation.

Antiviral combination treatment strategies for SARS-CoV-2 infection in immunocompromised patients.

The purpose of this review is to report the available evidence regarding the use of combination regimens of antivirals and/or antibody-based therapy in the treatment of SARS-CoV-2 in immunocompromised patients. Literature search identified 24 articles, excluding single case reports, which included mainly patients with hematological malignancies and/or B-cell depletion. Data were divided based on the timing and reason for administration of combination treatment, that is, early treatment to prevent progression to severe COVID-19 and treatment of prolonged or relapsed infection. We described the treated populations, treatment duration and composition of combination treatment. We briefly addressed new treatment options and we proposed an algorithm for the management of COVID-19 infection in patients affected by hematological malignancies. Combination treatment seems an effective (73-100%) and well tolerated (<5% reported bradycardia, hepatotoxicity, neutropenia) strategy for treating prolonged/relapsed SARS-CoV-2 infections in the immunocompromised host, although its optimal composition and duration cannot be defined based on the currently available evidence. The role of combination treatment as an early treatment strategy for immunocompromised patients at a high risk of progression to severe disease/persistent shedding requires further evidence from comparison with monotherapy, even though high efficacy was reported for combinations of antivirals plus mAbs in case of previous viral variants.

Real-world clinical outcomes of tixagevimab/cilgavimab in the Omicron outbreak in China: baseline characteristics and interim analysis of the CLEAR study

PurposeThis study aimed to investigate the real-world use and clinical outcomes of tixagevimab/cilgavimab in China during the Omicron outbreak in late 2022.MethodsThis observational, real-world study included patients who received tixagevimab/cilgavimab from July 9 to December 30, 2022, in Hainan, China. Here, we report the baseline and characteristics and interim analysis results of the clinical outcomes in those receiving at least one dose of tixagevimab/cilgavimab (300 mg) for pre-exposure prophylaxis.ResultsAmong 248 subjects who received tixagevimab/cilgavimab, 229 subjects were included in this analysis. Until March 28, 2023, the median follow-up was 95 days. The mean age of the subjects was 44.4 ± 15.9 years, 11.8% were ≥ 65 years, and 41.5% were male. Fifty-eight (25.3%) subjects had comorbidities, 16.2% subjects had key immune compromised conditions. Seventy-two (32.6%) patients had laboratory-confirmed SARS-CoV-2 infection and/or received healthcare within three months; 71/72 (98.6%) had mild disease, and one (1.4%) was moderate. No COVID-19-related intensive care unit (ICU) admissions, extracorporeal membrane oxygenation utilizations, or death occurred. Two (0.9%) patients required hospitalization. One (0.4%) serious adverse event occurred, which was considered unrelated to tixagevimab/cilgavimab.ConclusionAmong Chinese patients receiving prophylactic tixagevimab/cilgavimab, the incidence of COVID-19-related hospitalization, ICU admission, or death was low during the Omicron surge. Further randomized controlled trials with larger sample sizes are needed to determine the effectiveness of tixagevimab/cilgavimab in preventing severe COVID-19 outcomes.Trial registrationThe study was registered with clinicaltrial.gov (NCT05917951).