Association of the rs2814778 variant in theACKR1gene, responsible for the Duffy erythrocyte antigen "null" phenotype, with COVID-19 severity in Southern Brazil

BackgroundCOVID-19 has so far affected more than 250 million individuals worldwide, causing more than 5 million deaths. Several risk factors for severe disease have been identified, most of which coincide with advanced age. In younger individuals, severe COVID-19 often occurs in the absence of obvious comorbidities. Guided by the finding of cytomegalovirus (CMV)-specific T cells with some cross-reactivity to SARS-CoV-2 in a COVID-19 intensive care unit (ICU) patient, we decided to investigate whether CMV seropositivity is associated with severe or critical COVID-19.Herpes simplex virus (HSV) serostatus was investigated as control.MethodsNational German COVID-19 bio-sample and data banks were used to retrospectively analyze the CMV and HSV serostatus of patients who experienced mild (n = 101), moderate (n = 130) or severe to critical (n = 80) disease by IgG serology. We then investigated the relationship between disease severity and herpesvirus serostatus via statistical models.ResultsNon-geriatric patients (< 60 years) with severe COVID-19 were found to have a very high prevalence of CMV-seropositivity, while CMV status distribution in individuals with mild disease was similar to the prevalence in the German population; interestingly, this was not detectable in older patients. Prediction models support the hypothesis that the CMV serostatus, unlike HSV, might be a strong biomarker in identifying younger individuals with a higher risk of developing severe COVID-19, in particular in absence of other co-morbidities.ConclusionsWe identified ‘CMV-seropositivity’ as a potential novel risk factor for severe COVID-19 in non-geriatric individuals in the studied cohorts. More mechanistic analyses as well as confirmation of similar findings in cohorts representing the currently most relevant SARS-CoV-2 variants should be performed shortly.

COVID-19 has so far affected more than 250 million individuals worldwide, causing more than 5 million deaths. Several risk factors for severe disease have been identified, most of which coincide with advanced age. In younger individuals, severe COVID-19 often occurs in the absence of obvious comorbidities. Guided by the finding of cytomegalovirus (CMV)-specific T cells with some cross-reactivity to SARS-CoV-2 in a COVID-19 intensive care unit (ICU) patient, we decided to investigate whether CMV seropositivity is associated with severe or critical COVID-19. Herpes simplex virus (HSV) serostatus was investigated as control. National German COVID-19 bio-sample and data banks were used to retrospectively analyze the CMV and HSV serostatus of patients who experienced mild (n = 101), moderate (n = 130) or severe to critical (n = 80) disease by IgG serology. We then investigated the relationship between disease severity and herpesvirus serostatus via statistical models. Non-geriatric patients (< 60 years) with severe COVID-19 were found to have a very high prevalence of CMV-seropositivity, while CMV status distribution in individuals with mild disease was similar to the prevalence in the German population; interestingly, this was not detectable in older patients. Prediction models support the hypothesis that the CMV serostatus, unlike HSV, might be a strong biomarker in identifying younger individuals with a higher risk of developing severe COVID-19, in particular in absence of other co-morbidities. We identified 'CMV-seropositivity' as a potential novel risk factor for severe COVID-19 in non-geriatric individuals in the studied cohorts. More mechanistic analyses as well as confirmation of similar findings in cohorts representing the currently most relevant SARS-CoV-2 variants should be performed shortly.

A response to “Male balding is a major risk factor for severe COVID-19”

Background Cancer, cardiovascular disease, hypertension, diabetes, chronic kidney disorders, chronic lung disorders, neurological disorders, obesity, immunocompromisation, and schizophrenia or bipolar disorders were found to be risk factors for severe Covid-19. The aim was to determine associations between having such diagnoses and future sickness absence (SA) due to Covid-19 or related diagnoses in 2020. Methods A prospective population-based cohort study of all 299,268 blue-collar workers (48% women) in Sweden in 2018, using linked microdata from four nationwide registers covering 2018-2020. People with any of the above diagnoses in 2018 or 2019 were identified using microdata from specialised in- and outpatient healthcare and prescribed drugs. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of a new SA spell &amp;gt;14 days due to diagnosed Covid-19 or one of the diagnoses used by the Social Insurance Agency for suspected Covid-19 in 2020, separately for each diagnosis group and a global estimate for all risk factors together, adjusted for sociodemographic characteristics. Results In total, 38,422 individuals had at least one of the diagnoses that was a risk factor for severe Covid-19. Of them, 284 individuals had SA due to Covid-19 or related diagnoses (0.7%) in 2020, while 1210 of those with no such risk factor for Covid-19 had SA due to Covid-19 or related diagnoses (0.5%). The adjusted OR of SA due to Covid-19 or related diagnoses was 1.37 (95% CI 1.20-1.56) for those who had any risk factors for severe Covid-19. The group of diagnoses with the highest adjusted OR for SA in Covid-19-related diagnoses was lung disease (2.23; 95% CI 1.93-2.56). Conclusions While only a few of those with prior morbidity that was a risk factor for severe Covid-19 had SA due to Covid-19 or related diagnoses in 2020, they had a higher risk than those without such prior morbidity. Key messages • Having prior morbidity with a diagnosis identified as a risk factor for severe Covid-19 was associated with a higher risk of having SA due to Covid-19 or related diagnoses in 2020. • Prior lung disease was the diagnosis group with the highest risk of SA due to Covid-19 or related diagnoses.

COVID-19 in children is characterized by a predominance of mild and asymptomatic forms, along with frequent gastrointestinal symptoms. It is known that comorbid conditions are a risk factor for severe COVID-19 in children; however, the course of SARS-CoV-2 infection in children with chronic digestive system diseases remains under-researched. Objective. To identify the specific characteristics of COVID-19 in children with chronic digestive system diseases, assess risk factors for severe COVID-19, and evaluate the impact of immunosuppressive therapy on COVID-19 outcomes. Materials and Methods. A single-center cohort retrospective and prospective non-randomized study was conducted, including 74 patients with COVID-19 and chronic digestive system diseases and a control group of 30 patients with COVID-19 without comorbidities, all hospitalized in the infectious disease department of the Russian Children’s Clinical Hospital, Moscow, in 2022 and 2023. Results. Сhildren with underlying digestive system diseases were not at a higher risk of severe COVID-19 compared to the control group. Severe, uncontrolled somatic disease and the presence of two or more comorbidities were risk factors for complicated SARS-CoV-2 infection. The duration of detectable SARS-CoV-2 RNA in the study group was nine days. Conclusion. Patients with chronic digestive system diseases, including those receiving immunosuppressive therapy, do not appear to be at higher risk for severe or unfavorable COVID-19 outcomes; however, prolonged SARS-CoV-2 RNA shedding was observed. Risk factors for severe COVID-19 include the presence of two or more comorbidities and severe somatic disease.

Is COVID-19 infection more severe in kidney transplant recipients?

Study ObjectivesObstructive sleep apnea (OSA) has been proposed as a risk factor for severe COVID-19. Confounding is an important consideration as OSA is associated with several known risk factors for severe COVID-19. Our aim was to assess the association of OSA with hospitalization due to COVID-19 using a population-based cohort with detailed information on OSA and comorbidities.MethodsIncluded were all community-dwelling Icelandic citizens 18 years of age and older diagnosed with SARS-CoV-2 infection in 2020. Data on demographics, comorbidities, and outcomes of COVID-19 was obtained from centralized national registries. Diagnosis of OSA was retrieved from the centralized Sleep Department Registry at Landspitali – The National University Hospital. Severe COVID-19 was defined as the composite outcome of hospitalization and death. The associations between OSA and the outcome were expressed as odds ratios (OR) with 95% confidence intervals (95% CI), calculated using logistic regression models and inverse probability weighting.ResultsA total of 4,756 individuals diagnosed with SARS-CoV-2 infection in Iceland were included in the study (1.3% of the Icelandic population), of whom 185 had a diagnosis of OSA. In total, 238 were hospitalized or died, 38 of whom had OSA. Adjusted for age, sex, and BMI, OSA was associated with poor outcome (OR 2.2, 95% CI 1.4–3.5). This association was slightly attenuated (OR 2.0, 95% CI 2.0, 1.2–3.2) when adjusted for demographic characteristics and various comorbidities.ConclusionsOSA was associated with twofold increase in risk of severe COVID-19, and the association was not explained by obesity or other comorbidities.

Increased mortality among hypertensive COVID-19 patients: Pay a closer look on diuretics in mechanically ventilated patients

BackgroundObstructive sleep apnoea (OSA) is associated with higher body mass index (BMI), diabetes, older age and male gender, which are all risk factors for severe COVID-19.We aimed to study if...

Decision letter: Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population

Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007–2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids, and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1–3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7–11 years after blood sampling (2.6 [1.7–3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1–15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population.

Background:To understand a causal role of modifiable lifestyle factors in angiotensin-converting enzyme 2 (ACE2) expression (a putative severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] receptor) across 44 human tissues/organs, and in coronavirus disease 2019 (COVID-19) susceptibility and severity, we conducted a phenome-wide two-sample Mendelian randomization (MR) study.Methods:More than 500 genetic variants were used as instrumental variables to predict smoking and alcohol consumption. Inverse-variance weighted approach was adopted as the primary method to estimate a causal association, while MR-Egger regression, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to identify potential horizontal pleiotropy.Results:We found that genetically predicted smoking intensity significantly increased ACE2 expression in thyroid (β=1.468, p=1.8×10−8), and increased ACE2 expression in adipose, brain, colon, and liver with nominal significance. Additionally, genetically predicted smoking initiation significantly increased the risk of COVID-19 onset (odds ratio=1.14, p=8.7×10−5). No statistically significant result was observed for alcohol consumption.Conclusions:Our work demonstrates an important role of smoking, measured by both status and intensity, in the susceptibility to COVID-19.Funding:XJ is supported by research grants from the Swedish Research Council (VR-2018–02247) and Swedish Research Council for Health, Working Life and Welfare (FORTE-2020–00884).

Decision letter: Mendelian randomization analysis provides causality of smoking on the expression of ACE2, a putative SARS-CoV-2 receptor

Few real-world analyses of the ability of vaccines to protect against severe COVID-19 have been published. In this real-world study, we compared the prevalence of severe or critical COVID-19 between patients at our hospital who were not vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or who had been vaccinated partial, full, or booster course with the CoronaVac, containing inactivated virus propagated in Vero cells. Data from electronic health records were retrospectively analyzed for 4090 inpatients with COVID-19 who were treated at West China Hospital, Chengdu between December 6, 2022 and February 14, 2023. Clinicodemographic characteristics and COVID-19 severity were compared among patients who had been vaccinated 0, 1, 2 or more times with inactivated vaccine CoronaVac. To evaluate vaccine effectiveness over time, we plotted Kaplan-Meier curves with the percentage of patients with the outcome of severe or critical COVID-19 from the time of their last vaccine dose according to vaccination status. Ordinal logistic regression was used to assess associations between vaccination status and COVID-19 severity. Cox regression was used to identify risk factors for severe or critical COVID-19. Among the 4090 patients, 171 had been vaccinated partial and 423 twice with the full CoronaVac regimens, while 905 had been vaccinated three times (boosted). The prevalence of severe or critical COVID-19 among patients was 11 percentage points lower among those vaccinated (40%) at least twice than among those unvaccinated (51%) (p＜0.001), while it was 10% points lower among those who had received a booster (41%) than among those unvaccinated (51%) (p＜0.001). Protection against severe or critical COVID-19 due to vaccination was significantly weakened by being older than 65 years, being male, or having diabetes, chronic heart disease, autoimmune disease, or chronic lung disease. Completing a full course of immunization with inactivated vaccine CoronaVac against SARS-CoV-2 can reduce the risk of severe or critical COVID-19 due to the Omicron BA.5 subvariant.

Cardiometabolic disease is associated with mortality and requirement for ventilation in COVID-19. Symptomatic atherosclerotic cardiovascular disease (CVD) implies the presence of significant endothelial dysfunction and is a risk factor for severe COVID-19. However, many patients with no history of CVD exhibit severe COVID-19. We hypothesised that CVD risk calculators could serve as a proxy for significant endothelial dysfunction and predict COVID-19 outcomes in those without symptomatic CVD. We reviewed 230 patients aged 35 to 65 years, hospitalized with COVID-19 at our institution. 190 patients with no history of symptomatic CVD were included. 23% developed severe respiratory failure (RF, requiring mechanical or non-invasive ventilation), while 4% (7/164) of those without prior end-stage renal disease required renal replacement therapy (RRT). In univariate analysis, age (β = 0.057 ± 0.02, p= 0.02), BMI (β = 0.05 ± 0.03, p = 0.049) and T2DM (β = 0.81 ± 0.41, p = 0.048) predicted RF. In keeping with a link between insulin resistance and severe COVID-19, an association was observed between triglycerides and RF (β = 0.26 ± 0.14, P = 0.058). CVD risk indices QRISK3 (0.07 ± 0.02, P &amp;lt;0.001), a CVD Risk Algorithm that predicts the risk of a CV event in next 10 years, and CHADS2VASC (0.53 ± 0.20, P=0.01) were both associated with RF. Age and QRISK3 were associated with a requirement for RRT and length of stay. We observed a threshold effect for QRISK3: when 10 year risk of a CV event was &amp;gt; 5% the risk of RF markedly increased (OR: 6.86 (95% CI: 2.30 - 20.5, P&amp;lt;0.001). The risk of RF was similar across all strata of QRISK3 &amp;gt;5%. A similar trend was observed when analysis was limited to those with T2DM (Ventilatory support in T2DM: QRISK&amp;lt;5% - 0/8, QRISK&amp;gt;5%: 11/30). All cases of RRT occurred in those with QRISK &amp;gt;5%. CVD risk calculators predict severe COVID-19, supporting a role for subclinical CVD in severe COVID-19. Patients hospitalized with QRISK3 &amp;gt;5% may be candidates for early intervention and enhanced monitoring. Disclosure S. Lockhart: None. A. Sheikh: None. H. Griffiths: None. J. Calvo latorre: None. A. B. Daly: None. L. Sibal: None. Funding National Institute for Health Research