A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity.

BACKGROUND: Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation contradicts each other. We therefore systematically investigated the genetic causal correlations between various ADs and COVID-19 infection/severity. METHODS: We performed a two-sample, bidirectional Mendelian randomization (MR) study for five types of ADs and the latest round of COVID-19 GWAS meta-analysis datasets (critically ill, hospitalized, and infection cases). We also further validated the significant causal correlations and elucidated the potential underlying molecular mechanisms. RESULTS: With the most suitable MR method, asthma consistently demonstrated causal protective effects on critically ill and hospitalized COVID-19 cases (OR < 0.93, p < 2.01 × 10-2), which were further confirmed by another validated GWAS dataset (OR < 0.92, p < 4.22 × 10-3). In addition, our MR analyses also observed significant causal correlations of food allergies such as shrimp allergy with the risk of COVID-19 infection/severity. However, we did not find any significant causal effect of COVID-19 phenotypes on the risk of ADs. Regarding the underlying molecular mechanisms, not only multiple immune-related cells such as CD4+ T, CD8+ T and the ratio of CD4+/CD8+ T cells showed significant causal effects on COVID-19 phenotypes and various ADs, the hematology traits including monocytes were also significantly correlated with them. Conversely, various ADs such as asthma and shrimp allergy may be causally correlated with COVID-19 infection/severity by affecting multiple hematological traits and immune-related cells. CONCLUSIONS: Our systematic and bidirectional MR analyses suggest a unidirectional causal effect of various ADs, particularly of asthma on COVID-19 infection/severity, but the reverse is not true. The potential underlying molecular mechanisms of the causal effects call for more attention to clinical monitoring of hematological cells/traits and may be beneficial in developing effective therapeutic strategies for allergic patients following infection with COVID-19.

Results of the Cologne Corona Surveillance (CoCoS) project- a cross-sectional study: survey data on risk factors of SARS-CoV-2 infection, and moderate-to-severe course in primarily immunized adults.

BACKGROUND: Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey. METHODS: The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants' demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model. RESULTS: A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415-0.823) and older age (HR = 0.974, 95%CI 0.966-0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949-0.977). Female sex (HR = 2.570, 95%CI1.435-4.603), smoking (HR = 1.965, 95%CI1.147-3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465-5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection. CONCLUSION: The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Age-specific contribution of contacts to transmission of SARS-CoV-2 in Germany.

Current estimates of pandemic SARS-CoV-2 spread in Germany using infectious disease models often do not use age-specific infection parameters and are not always based on age-specific contact matrices of the population. They also do usually not include setting- or pandemic phase-based information from epidemiological studies of reported cases and do not account for age-specific underdetection of reported cases. Here, we report likely pandemic spread using an age-structured model to understand the age- and setting-specific contribution of contacts to transmission during different phases of the COVID-19 pandemic in Germany. We developed a deterministic SEIRS model using a pre-pandemic contact matrix. The model was optimized to fit age-specific SARS-CoV-2 incidences reported by the German National Public Health Institute (Robert Koch Institute), includes information on setting-specific reported cases in schools and integrates age- and pandemic period-specific parameters for underdetection of reported cases deduced from a large population-based seroprevalence studies. Taking age-specific underreporting into account, younger adults and teenagers were identified in the modeling study as relevant contributors to infections during the first three pandemic waves in Germany. For the fifth wave, the Delta to Omicron transition, only age-specific parametrization reproduces the observed relative and absolute increase in pediatric hospitalizations in Germany. Taking into account age-specific underdetection did not change considerably how much contacts in schools contributed to the total burden of infection in the population (up to 12% with open schools under hygiene measures in the third wave). Accounting for the pandemic phase and age-specific underreporting is important to correctly identify those groups of the population in which quarantine, testing, vaccination, and contact-reduction measures are likely to be most effective and efficient. Age-specific parametrization is also highly relevant to generate informative age-specific output for decision makers and resource planers.

Abdominal and Chest Ultrasonography: A predictor for disease progression in nonsevere dengue.

Background: Dengue is one of the most rapidly spreading arboviral infections in the world. Ultrasound is well established in abdomino-thoracic evaluation of patients with dengue infection. The aim of this study was to explore the role of ultrasound in predicting occurrence of severe infection in dengue patients and in predicting deterioration in patients with nonsevere dengue. Methods: The serologically proven dengue patients who reported to hospital during the study period were divided into three categories based on the dengue infection severity score. Ultrasound findings of abdomen and chest in these patients were noted in the initial, as well as follow-up scans and inferences drawn. Results: 61% belonged to the category of Dengue Fever, 35% were in Dengue Hemorrhagic Fever category, and 4% had Dengue Shock Syndrome. Positive ultrasound findings were seen to be significantly higher in patients with severe dengue. Logistic regression analysis revealed the presence of pericholecystic fluid to be significantly associated with the severe disease, while the presence of gall bladder wall edema, ascites, and any ultrasound finding were significantly associated with the disease progression. The odds of a patient with severe dengue having gall bladder wall edema, ascites, or any ultrasound finding were 2.74, 2.04, and 2.619 times, respectively. Conclusion: Our study indicates that positive findings on ultrasound are significantly higher in severe dengue and also that ultrasound can be reliably used to identify the patients with nonsevere dengue who are likely to progress to severe dengue.

Smoking status and SARS-CoV-2 infection severity among Lebanese adults: a cross-sectional study.

BACKGROUND: A paradoxical hypothesis about the effect of smoking on patients infected with severe acute respiratory syndrom 2 (SARS-CoV-2) infection still exists. Furthermore, gender-discrepancy in the impact of smoking on COVID-19 severity was given little attention. Thus, the aims of the present study were to evaluate the prevalence of smoking and the COVID-19 infection severity in a sample of adult patients diagnosed with COVID-19 and to explore the relationship between smoking status and SARS-CoV-2 infection severity in the overall sample and stratified by gender. METHODS: A retrospective analytical study was conducted on patients diagnosed with COVID-19 cases between December, 2020 and April, 2021 from three leading laboratories in Lebanon. Sociodemographic characteristics, smoking status and clinical symptoms were collected. Multinomial logistic regression analysis was used to explore the relationship between smoking status and SARS-CoV-2 infection severity. RESULTS: A total of 901 confirmed COVID-19 cases participated in the study, 50.8% were females. The mean age of patients was 38.4 years (SD = 15.3). Of the total sample, 521(57.8%) were current smokers. Regarding infection severity, 14.8% were asymptomatic, 69.9% had mild symptoms, while 15.3% had severe infection. In the overall sample, smoking status, smoking types and dose-response were not significantly associated with infection severity. Upon stratifying the entire sample by gender, no association was found between all the considered variables with infection severity among females. However, a significant association was found among male with mild infection compared to their asymptomatic counterparts (OR = 1.78 95% CI (1.01-3.13)). Waterpipe smoking was found to be associated with infection severity among male with mild infection (OR 2.64 (95% CI 1.32-5.27)) and severe infection 2.79, 95% CI (1.19-6.53) compared to their asymptomatic counterparts. CONCLUSION: Our fundings highlight sex differences in the association between tobacco smoking and COVID-19 severity. Current tobacco smoking was not associated with SARS-CoV-2 infection severity among female patients, however, tobacco smoking, particularly waterpipe, was found to be associated with infection severity among male. Thus, the battle against smoking should continue by assisting smokers to successfully and permanently quit.

Changes in the intestinal microbiota of Pacific white shrimp (Litopenaeus vannamei) with different severities of Enterocytozoon hepatopenaei infection.

The intestinal microbiota of the Pacific white shrimp Litopenaeus vannamei during Enterocytozoon hepatopenaei (EHP) infection was investigated by 16S rRNA gene-based analysis. The results showed that bacterial diversity in the intestine of L. vannamei was high, but it decreased with increasing severity of EHP infection. The relative abundances of the phyla Planctomycetes, Actinobacteria and Acidobacteria decreased significantly with a decrease in body size or EHP infection severity (P < 0.05). The most abundant genera were Pseudomonas, Methylobacterium, Bradyrhizobium, Bacteroides, Vibrio, Prevotella and so on. In addition, the relative abundances of some bacteria, such as Pseudomonas, Bradyrhizobium, Bacteroides and Vibrio, increased significantly with a decrease in body size or EHP infection severity (P < 0.05). These findings suggest that changes in the intestinal microbiota occur depending on the severity of EHP infection.

Correlation between lung infection severity and clinical laboratory indicators in patients with COVID-19: a cross-sectional study based on machine learning.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic that has raised worldwide concern. This study aims to investigate the correlation between the extent of lung infection and relevant clinical laboratory testing indicators in COVID-19 and to analyse its underlying mechanism. METHODS: Chest high-resolution computer tomography (CT) images and laboratory examination data of 31 patients with COVID-19 were extracted, and the lesion areas in CT images were quantitatively segmented and calculated using a deep learning (DL) system. A cross-sectional study method was carried out to explore the differences among the proportions of lung lobe infection and to correlate the percentage of infection (POI) of the whole lung in all patients with clinical laboratory examination values. RESULTS: No significant difference in the proportion of infection was noted among various lung lobes (P > 0.05). The POI of total lung was negatively correlated with the peripheral blood lymphocyte percentage (L%) (r = - 0.633, P < 0.001) and lymphocyte (LY) count (r = - 0.555, P = 0.001) but positively correlated with the neutrophil percentage (N%) (r = 0.565, P = 0.001). Otherwise, the POI was not significantly correlated with the peripheral blood white blood cell (WBC) count, monocyte percentage (M%) or haemoglobin (HGB) content. In some patients, as the infection progressed, the L% and LY count decreased progressively accompanied by a continuous increase in the N%. CONCLUSIONS: Lung lesions in COVID-19 patients are significantly correlated with the peripheral blood lymphocyte and neutrophil levels, both of which could serve as prognostic indicators that provide warning implications, and contribute to clinical interventions in patients.

Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection, Atlanta, Georgia, USA, 2020.

Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.

Evolution of Compatibility Range in the Rice-Magnaporthe oryzae System: An Uneven Distribution of R Genes Between Rice Subspecies.

Efficient strategies for limiting the impact of pathogens on crops require a good understanding of the factors underlying the evolution of compatibility range for the pathogens and host plants, i.e., the set of host genotypes that a particular pathogen genotype can infect and the set of pathogen genotypes that can infect a particular host genotype. Until now, little is known about the evolutionary and ecological factors driving compatibility ranges in systems implicating crop plants. We studied the evolution of host and pathogen compatibility ranges for rice blast disease, which is caused by the ascomycete Magnaporthe oryzae. We challenged 61 rice varieties from three rice subspecies with 31 strains of M. oryzae collected worldwide from all major known genetic groups. We determined the compatibility range of each plant variety and pathogen genotype and the severity of each plant-pathogen interaction. Compatibility ranges differed between rice subspecies, with the most resistant subspecies selecting for pathogens with broader compatibility ranges and the least resistant subspecies selecting for pathogens with narrower compatibility ranges. These results are consistent with a nested distribution of R genes between rice subspecies.

Changes in the expression of COI1, TIR1, and ERF1 genes and respective MiRNAs in Fusarium basal Rot-Stressed onion.

Fusarium oxysporum f.sp. cepae (FOC), as basal rot fungus, is the most detrimental pathogen causing a serious threat to onion productivity in the world. In this study, we first determined FOC tolerance in seven Iranian onion cultivars, two known international onions (Texas Early Grano and Sweet Yellow Spanish), and an Allium species related to the onion (Allium asarence) based on the infection severity. Then, a transcriptional screen was performed by comparing the transcript levels of some pathogen-responsive genes (ERF1, COI1, and TIR1) and their predicted miRNAs in the sensitive (Ghermeze Azarshahr Cv.) and the resistant (A. asarence) onions to determine key genes and their miRNAs involved in the defense responses of onions to FOC. From our results, a difference was found in the COI1 and ERF1 expression 48 h after inoculation with FOC as compared to the respective 24 and 72 h. It can be explained by either special mechanisms involved in raising energy consumption efficiency or the interactive effects of other genes in the jasmonic acid (JA) and ethylene (ET) signaling pathways. Moreover, expression analysis of the pathogen-responsive genes and their targeting miRNAs identified the miR-5629, which targets the COI1 gene as a likely key factor in conferring resistance in the FOC-resistant onion, i.e., A. asarence. However, exploring the function of the miRNA/target pair is highly recommended to deeply understand the effect of the miRNA/target pair-associated pathway in the control of A. asarense-FOC interaction.

Virulence is associated with daily rhythms in the within-host replication of the malaria parasite Plasmodium chabaudi.

Most malaria (Plasmodium spp.) parasite species undergo asexual replication synchronously within the red blood cells of their vertebrate host. Rhythmicity in this intraerythrocytic developmental cycle (IDC) enables parasites to maximise exploitation of the host and align transmission activities with the time of day that mosquito vectors blood feed. The IDC is also responsible for the major pathologies associated with malaria, and plasticity in the parasite's rhythm can confer tolerance to antimalarial drugs. Both the severity of infection (virulence) and synchrony of the IDC vary across species and between genotypes of Plasmodium; however, this variation is poorly understood. The theory predicts that virulence and IDC synchrony are negatively correlated, and we tested this hypothesis using two closely related genotypes of the rodent malaria model Plasmodium chabaudi that differ markedly in virulence. We also test the predictions that, in response to perturbations to the timing (phase) of the IDC schedule relative to the phase of host rhythms (misalignment), the virulent parasite genotype recovers the correct phase relationship faster, incurs less fitness losses and so hosts benefit less from misalignment when infected with a virulent genotype. Our predictions are partially supported by results suggesting that the virulent parasite genotype is less synchronous in some circumstances and recovers faster from misalignment. While hosts were less anaemic when infected by misaligned parasites, the extent of this benefit did not depend on parasite virulence. Overall, our results suggest that interventions to perturb the alignment between the IDC schedule, and host rhythms and increase synchrony between parasites within each IDC, could alleviate disease symptoms. However, virulent parasites, which are better at withstanding conventional antimalarial treatment, would also be intrinsically better able to tolerate such interventions.

Comparison of infection severity of vaccinated and unvaccinated health workers with Corona Virus: A cohort study.

BACKGROUND: Hospital staff members are most susceptible to the COVID-19 illness, which is currently prevented through vaccination. Hospital staff members also refuse vaccinations, albeit the underlying causes have not been identified. The study aimed to compare the severity of the symptoms of the disease on the body for health workers who took the coronavirus vaccine and those who did not take the vaccine. MATERIALS AND METHODS: This cohort study aimed to estimate the of infection severity of vaccinated and unvaccinated health workers with Corona Virus in Mosul Hospital, Iraq. Data were obtained from the General Mosul Hospital, Nineveh, Iraq. The first of the three components of this questionnaire outlined the demographic characteristics. Second part: First group of unvaccinated Health care workers included those who had not received the COVID-19 immunization or had only gotten one dose of the vaccine; the second group included those who had received their first dose of Corona vaccine and the third group included those who had received two doses of Corona Vaccine. HCWs who got corona vaccine were included in the three-dose final group. RESULTS: The study's findings indicate that as compared to the corona vaccination, the vaccinated experienced less severe infection symptoms and fewer dosage stays. The high share of healthcare workers among the 20- to 30-year-olds who received vaccinations accounts for the gender gap between the vaccinated and unvaccinated groups. CONCLUSION: This study concluded that the results of the corona vaccine are not consistent among the various groups of HCWs. The acceptability of vaccinations is practically unanimous among nurses, but less so among doctors and other healthcare professionals.

Relationship between leptin and white blood cells: a potential role in infection susceptibility and severity-the Olivetti Heart Study.

A number of evidence showed an emerging role of leptin on immune system, involving inflammation, and innate and adaptive immunity. Few observational studies have evaluated the relationship between leptin and immunity, albeit with low statistical power and methodological differences. Therefore, the aim of this study was to evaluate the potential role of leptin on the immunity, expressed as white blood cells (WBC)-and its subpopulations, by comprehensive multivariate models in a sample of adult men. A cross-sectional evaluation of a general population comprised 939 subjects participating in the Olivetti Heart Study, with available leptin levels and WBC-and its subpopulations. WBC were significantly and positively associated with leptin, C-reactive protein and HOMA index (p < 0.05), but not with age and anthropometric indices (p > 0.05). The multivariate analysis confirmed the association between leptin and WBC, after accounting for main confounders (p < 0.05). Additional analysis on WBC subpopulations showed a positive and significant correlation between leptin and lymphocytes, monocytes and eosinophils (p < 0.05), but not with neutrophils and basophils (p > 0.05). After stratification by body weight, the positive and significant association between leptin and WBC-and its subpopulations-was found in excess body weight participants. The results of this study indicate a direct relationship between leptin levels and WBC-and its subpopulations-in excess body weight participants. These results support the hypothesis that leptin has modulatory functions on immunity and role in the pathophysiology of immune-related diseases, in particular in those associated with excess body weight.

Community-Acquired Severe Clostridium difficile Enteritis Complicated by Metabolic Acidosis and Acute Kidney Injury.

Clostridium difficile (CD) is known to be pathogenic when the balance of intestinal microbiota is disrupted by the administration of broad-spectrum antimicrobial agents. Therefore, CD enteritis is often suspected in cases of hospital-onset diarrhea. There has been a rise in the incidence of community-acquired CD enteritis in recent years in the United States. In this report, we present a case of a 57 year-old-man who was admitted to the emergency department with abdominal distension and dyspnea. The patient suffered from acute renal failure and metabolic acidosis from enteritis. He required mechanical ventilation and continuous renal replacement therapy (CRRT) in the ICU. Analysis of the patient's stool sample on admission revealed the presence of CD antigens, and the prompt administration of metronidazole led to swift improvement. No studies have investigated the actual incidence of community-acquired CD enteritis infection in Japan. Since 20% of community-acquired CD enteritis cases have been reported as severe, all cases of community-acquired enteritis should raise concerns for CD enteritis. CD antigen/toxin in the stool should then be determined promptly before administering antibiotics.

The same boat, different storm: stress volatile emissions in response to biotrophic fungal infections in primary and alternate hosts.

Rust infection results in stress volatile emissions, but due to the complexity of host-pathogen interaction and variations in innate defense and capacity to induce defense, biochemical responses can vary among host species. Fungal-dependent modifications in volatile emissions have been well documented in numerous host species, but how emission responses vary among host species is poorly understood. Our recent experiments demonstrated that the obligate biotrophic crown rust fungus (P. coronata) differently activated primary and secondary metabolic pathways in its primary host Avena sativa and alternate host Rhamnus frangula. In A. sativa, emissions of methyl jasmonate, short-chained lipoxygenase products, long-chained saturated fatty acid derivatives, mono- and sesquiterpenes, carotenoid breakdown products, and benzenoids were initially elicited in an infection severity-dependent manner, but the emissions decreased under severe infection and photosynthesis was almost completely inhibited. In R. frangula, infection resulted in low-level induction of stress volatile emissions, but surprisingly, in enhanced constitutive isoprene emissions, and even severely-infected leaves maintained a certain photosynthesis rate. Thus, the same pathogen elicited a much stronger response in the primary than in the alternate host. We argue that future work should focus on resolving mechanisms of different fungal tolerance and resilience among primary and secondary hosts.

Factors Associated with Infection Severity of Diabetic Foot Ulcers: A Cross-Sectional Study.

Background: Infection in the ulcerated foot is a foremost cause of morbidity, constituting the biggest proportion of hospitalization and amputation among patients with diabetic foot ulcers. Assessment of infection severity lays a foundation for making treatment decisions, for which the IDSA/IWGDF classification is recommended. Different factors may cause various severity of infection. However, few investigations have been conducted concerning factors associated with infection severity of diabetic foot ulcers. Objective: To investigate factors associated with infection severity of diabetic foot ulcers. Methods: This cross-sectional study involved 150 subjects hospitalized in the Department of Endocrinology of Sun Yat-sen Memorial Hospital in Guangdong Province between July 2020 and September 2021. The IDSA/IWGDF classification was adopted to assess ulcer infection severity. Demographic and disease information, laboratory reports, and ulcer assessment results were evaluated for an association with the infection severity. The generalized linear model was performed to conduct multivariate analyses of the factors associated with the severity of foot infection. Results: The prevalence of mild, moderate, and severe infected diabetic foot was 23.3%, 64.7% and 10.2%, respectively. The results of generalized linear models showed a correlation between Alb (OR = -1.74, 95%CI1.12-6.58, p = .023), CRP (OR = 2.13, 95%CI1.38-7.21, p = .014), PCT (OR = 2.01, 95%CI1.29-7.64, p = .013), microbial type (OR = 2.04, 95%CI1.43-7.83, p = .004) and ulcer infection severity. Conclusion: Alb, CRP, PCT and microbial type were among the factors influencing infection severity of diabetic foot ulcers.

Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population.

Genetic and non-genetic factors are responsible for the high interindividual variability in the response to SARS-CoV-2. Although numerous genetic polymorphisms have been identified as risk factors for severe COVID-19, these remain understudied in Latin-American populations. This study evaluated the association of non-genetic factors and three polymorphisms: ACE rs4646994, ACE2 rs2285666, and LZTFL1 rs11385942, with COVID severity and long-term symptoms by using a case-control design. The control group was composed of asymptomatic/mild cases (n = 61) recruited from a private laboratory, while the case group was composed of severe/critical patients (n = 63) hospitalized in the Hospital Universitario Mayor-Méderi, both institutions located in Bogotá, Colombia. Clinical follow up and exhaustive revision of medical records allowed us to assess non-genetic factors. Genotypification of the polymorphism of interest was performed by amplicon size analysis and Sanger sequencing. In agreement with previous reports, we found a statistically significant association between age, male sex, and comorbidities, such as hypertension and type 2 diabetes mellitus (T2DM), and worst outcomes. We identified the polymorphism LZTFL1 rs11385942 as an important risk factor for hospitalization (p < 0.01; OR = 5.73; 95% CI = 1.2-26.5, under the allelic test). Furthermore, long-term symptoms were common among the studied population and associated with disease severity. No association between the polymorphisms examined and long-term symptoms was found. Comparison of allelic frequencies with other populations revealed significant differences for the three polymorphisms investigated. Finally, we used the statistically significant genetic and non-genetic variables to develop a predictive logistic regression model, which was implemented in a Shiny web application. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC = 0.86; 95% confidence interval 0.79-0.93). These results suggest that LZTFL1 rs11385942 may be a potential biomarker for COVID-19 severity in addition to conventional non-genetic risk factors. A better understanding of the impact of these genetic risk factors may be useful to prioritize high-risk individuals and decrease the morbimortality caused by SARS-CoV2 and future pandemics.

Characterizing Macrophages Diversity in COVID-19 Patients Using Deep Learning.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for coronavirus disease 2019 (COVID-19), has affected the lives of billions and killed millions of infected people. This virus has been demonstrated to have different outcomes among individuals, with some of them presenting a mild infection, while others present severe symptoms or even death. The identification of the molecular states related to the severity of a COVID-19 infection has become of the utmost importance to understanding the differences in critical immune response. In this study, we computationally processed a set of publicly available single-cell RNA-Seq (scRNA-Seq) data of 12 Bronchoalveolar Lavage Fluid (BALF) samples diagnosed as having a mild, severe, or no infection, and generated a high-quality dataset that consists of 63,734 cells, each with 23,916 genes. We extended the cell-type and sub-type composition identification and our analysis showed significant differences in cell-type composition in mild and severe groups compared to the normal. Importantly, inflammatory responses were dramatically elevated in the severe group, which was evidenced by the significant increase in macrophages, from 10.56% in the normal group to 20.97% in the mild group and 34.15% in the severe group. As an indicator of immune defense, populations of T cells accounted for 24.76% in the mild group and decreased to 7.35% in the severe group. To verify these findings, we developed several artificial neural networks (ANNs) and graph convolutional neural network (GCNN) models. We showed that the GCNN models reach a prediction accuracy of the infection of 91.16% using data from subtypes of macrophages. Overall, our study indicates significant differences in the gene expression profiles of inflammatory response and immune cells of severely infected patients.

Sex- and gender-related differences linked to SARS-CoV-2 infection among the participants in the web-based EPICOVID19 survey: the hormonal hypothesis.

Objective To investigate sex- and gender-based differences linked to SARS-COV-2 infection and to explore the role of hormonal therapy (HT) in females. Study design Data from the self-administered, cross-sectional, web-based EPICOVID19 survey of 198,822 adults living in Italy who completed an online questionnaire during the first wave of the epidemic in Italy (April-May 2020) were analyzed. Main outcomes measures Multivariate binary logistic and multinomial regression models were respectively used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) for positive nasopharyngeal swab (NPS) test results and severe SARS-CoV-2 infection. Results The data from 6,873 participants (mean age 47.9 ± 14.1 years, 65.8% females) who had a known result from an NPS test were analyzed. According to the multivariate analysis, females had lower odds of a positive result from the NPS test (aOR 0.75, 95%CI 0.66-0.85) and of having a severe infection (aOR 0.46, 95%CI 0.37-0.57) than did their male counterparts. These differences were greater with decreasing age in both sexes. In addition, females aged ≥60 years receiving HT (N = 2,153, 47.6%) had a 46% lower probability of having a positive NPS test (aOR 0.54, 95%CI 0.36-0.80) than their same-aged peers who had never used HT; there were no differences in the younger age groups with respect to HT status. Conclusion Female sex was associated with an age-dependent lower risk of having a severe SARS-CoV-2 infection than their male counterparts. Age seemed to modify the relationship between HT status and infection: while the two were not related among younger participants, it was negative in the older ones. Future prospective studies are needed to elucidate the potential protective role sex hormones may play. Trial registration ClinicalTrials.gov NCT04471701.

Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85.

OBJECTIVES: Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways. Here, we aimed to provide proof of concept for a novel solution to reduce the burden and potential long-term sequelae of severe early-life respiratory viral infection through maternal oral treatment during pregnancy with OM-85, already in widespread human clinical use. METHODS: In this study, we performed flow cytometry and targeted gene expression (RT-qPCR) analysis on lungs from neonatal offspring whose mothers received oral OM-85 treatment during pregnancy. We next determined whether neonatal offspring from OM-85 treated mothers demonstrate enhanced protection against lethal lower respiratory infection with mouse-adapted rhinovirus (vMC0), and associated lung immune changes. RESULTS: Offspring from mothers treated with OM-85 during pregnancy display accelerated postnatal seeding of lung myeloid populations demonstrating upregulation of function-associated markers. Offspring from OM-85 mothers additionally exhibit enhanced expression of TLR4/7 and the IL-1ß/NLRP3 inflammasome complex within the lung. These treatment effects were associated with enhanced capacity to clear an otherwise lethal respiratory viral infection during the neonatal period, with concomitant regulation of viral-induced IFN response intensity. CONCLUSION: These results demonstrate that maternal OM-85 treatment protects offspring against lethal neonatal respiratory viral infection by accelerating development of innate immune mechanisms crucial for maintenance of local immune homeostasis in the face of pathogen challenge.