Association between mannose binding lectin gene polymorphisms and clinical severity of COVID-19 in children.

BACKGROUND: Mannose-binding lectin (MBL) is a member of innate immunity and acts with MASP (MBL-associated serine protease) to activate the lectin pathway of the complement system. MBL gene polymorphisms are associated with susceptibility to infectious diseases. This study investigated whether MBL2 genotype, serum MBL levels, and serum MASP-2 levels affect the course of SARS-CoV-2 infection. METHODS AND RESULTS: Pediatric patients diagnosed with COVID-19 by positive real-time polymerase chain reaction (PCR) were included in the study. Single nucleotide polymorphisms in the promoter and exon 1 in the MBL2 gene (rs11003125, rs7096206, rs1800450, rs1800451, rs5030737) were identified by a PCR and restriction fragment length polymorphisms analysis. Serum MBL and MASP-2 levels were measured by ELISA. COVID-19 patients were divided into asymptomatic and symptomatic. Variables were compared between these two groups. A total of 100 children were included in the study. The mean age of the patients was 130 ± 67.2 months. Of the patients, 68 (68%) were symptomatic, and 32 (32%) were asymptomatic. The polymorphisms in the - 221nt and - 550nt promoter regions did not differ between groups (p > 0.05). All codon 52 and codon 57 genotypes were determined as wild-type AA. AB genotypes were found 45.6% in symptomatic patients while 23.5% in asymptomatics. Moreover, BB genotype was detected 9.4% in symptomatic and 6.3% in asymptomatic patients (p < 0.001). B allele was more frequent in symptomatic patients (46.3%) compared to asymptomatic patients (10.9%). (p < 0.001). Serum MBL and MASP-2 levels did not differ statistically between the groups (p = 0.295, p = 0.073). CONCLUSION: These findings suggest that codon 54 polymorphism in the MBL2 gene exon-1 region can be associated with the symptomatic course of COVID-19.

Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a devastating pandemic that causes disease with a variability in susceptibility and mortality based on variants of various clinical and demographic factors, including particular genes among populations. OBJECTIVES: Determine associations of demographic, clinical, laboratory, and single nucleotide polymorphisms in the ACE2, TMPRSS2, TNF-α, and IFN-γ genes to the incidence of infection and mortality in COVID-19 patients. DESIGN: Prospective cohort study SETTINGS: Various cities in the Kurdistan Region of Iraq. PATIENTS AND METHODS: This prospective cohort study compared laboratory markers (D-dimer, tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], C-reactive protein [CRP], lymphocyte and neutrophil counts) between COVID-19 patients and healthy controls. DNA was extracted from blood, and genotypes were done by Sanger sequencing. MAIN OUTCOME MEASURES: Single nucleotide polymorphisms of the ACE2, TMPRSS2, TNF-α, and IFN-γ genes and demographic characteristics and laboratory markers for predicting mortality in COVID-19. SAMPLE SIZE: 203 (153 COVID-19 patients, 50 health control subjects). RESULTS: Forty-eight (31.4%) of the COVID-19 patients died. Age over 40 and comorbidities were risk factors for mortality, but the strongest associations were with serum IFN-γ, the neutrophil-to-lymphocyte ratio (NLR), and serum TNF-α. The AA genotype and A allele of TMPRSS2 rs2070788 decreased while the GA genotype and A allele of TNF-α increased susceptibility to COVID-19. Patients with the GA genotype of TNF-α rs1800629 had shorter survival times (9.9 days) than those carrying the GG genotype (18.3 days) (P<.0001 by log-rank test). The GA genotype versus the GG genotype was associated with higher levels of serum TNF-α. The GA genotype increased mortality rates by up to 3.8 fold. The survival rate for COVID-19 patients carrying the IFN-γ rs2430561 TT genotype (58.5%) was lower than in patients with the TA and AA genotypes (80.3%). The TT genotype increased the risk of death (HR=3.664, P<.0001) and was linked to high serum IFN-γ production. Olfactory dysfunction was a predictor of survival among COVID-19 patients. CONCLUSIONS: Age older than 40, comorbidities, the NLR and particular genotypes for and the IFN-γ and TNF-α genes were risk factors for death. Larger studies in different populations must be conducted to validate the possible role of particular SNPs as genetic markers for disease severity and mortality in COVID-19 disease. LIMITATIONS: Small sample size. CONFLICT OF INTEREST: None.

Genotypic Diversity of Childhood Rhinovirus Infections.

Our objective was to describe the distribution of rhinovirus (RV) by species and type in both symptomatic and asymptomatic children in a prospective study over multiple years. A large and diverse distribution of RV types was seen among children with and without symptoms. RV-A and RV-C were predominant at all visits.

Association of IFIH1 and DDX58 genes polymorphism with susceptibility to COVID-19.

Pattern recognition receptors of the innate immune system, such as RIG-I and MDA5, are responsible for recognizing viruses and inducing interferon production. Genetic polymorphisms in the coding regions of RLR may be associated with the severity of COVID-19. Considering the contribution of the RLR signaling in immune-mediated reactions, this study investigated the association between three SNP in the coding region of IFIH1 and DDX58 genes with the susceptibility to COVID-19 in the Kermanshah population, Iran. 177 patients with severe and 182 with mild COVID-19 were admitted for this study. Genomic DNA was extracted from peripheral blood leukocytes of patients to determine the genotypes of two SNPs, rs1990760(C>T) and rs3747517(T>C) IFIH1 gene and rs10813831(G>A) DDX58 gene using PCR-RFLP method. Our results showed that the frequency of the AA genotype of rs10813831(G>A) was associated with susceptibility to COVID-19 compared to the GG genotype (p = 0.017, OR = 2.593, 95% CI 1.173-5.736). We also observed a statistically significant difference in the recessive model for SNPs rs10813831 variant (AA versus GG + GA, p = 0.003, OR = 2.901, 95% CI 1.405-6.103). Furthermore, No significant association was found between rs1990760 (C>T) and rs3747517(T>C) of IFIH1 gene polymorphisms with COVID-19. Our findings suggest that DDX58 rs10813831(A>G) polymorphism may be associated with COVID-19 severity in the Kermanshah population, Iran.

Association of Polymorphisms of IL-6 Pathway Genes (IL6, IL6R and IL6ST) with COVID-19 Severity in an Amazonian Population.

Interleukin-6 has been recognized as a major role player in COVID-19 severity, being an important regulator of the cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of the IL-6 pathway, namely IL6, IL6R, and IL6ST, may provide valuable prognostic/predictive markers for COVID-19. The present cross-sectional study genotyped three SNPs (rs1800795, rs2228145, and rs7730934) at IL6. IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As a control group, published data on gene and genotype frequencies were gathered from published studies before the pandemic started. Our major results point to an association of the IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion, the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidence from the literature about the association of these genotypes with mortality rates, pneumonia, and heightening of protein plasmatic levels pro-inflammatory driven effects.

Respiratory syncytial virus surge in 2022 caused by lineages already present before the COVID-19 pandemic.

In 2022, Austria experienced a severe respiratory syncytial virus (RSV) epidemic with an earlier-than-usual start (Weeks 35/2021-45/2022) and increased numbers of pediatric patients in emergency departments. This surge came 2 years after a season with no cases detected as a result of coronavirus disease 2019 nonpharmaceutical interventions. We analyzed epidemiologic patterns and the phylodynamics of RSV based on approximately 30 800 respiratory specimens collected year-round over 10 years from ambulatory and hospitalized patients from 248 locations in Austria. Genomic surveillance and phylogenetic analysis of 186 RSV-A and 187 RSV-B partial glycoprotein sequences collected from 2018 to 2022 revealed that the 2022/2023 surge was driven by RSV-B in contrast to the surge in the 2021/2022 season that was driven by RSV-A. Whole-genome sequencing and phylodynamic analysis indicated that the RSV-B strain GB5.0.6a was the predominant genotype in the 2022/2023 season and emerged in late 2019. The results provide insight into RSV evolution and epidemiology that will be applicable to future monitoring efforts with the advent of novel vaccines and therapeutics.

Genetic Analysis of Dengue Virus in Severe and Non-Severe Cases in Dhaka, Bangladesh, in 2018-2022.

Dengue virus (DENV) infections have unpredictable clinical outcomes, ranging from asymptomatic or minor febrile illness to severe and fatal disease. The severity of dengue infection is at least partly related to the replacement of circulating DENV serotypes and/or genotypes. To describe clinical profiles of patients and the viral sequence diversity corresponding to non-severe and severe cases, we collected patient samples from 2018 to 2022 at Evercare Hospital Dhaka, Bangladesh. Serotyping of 495 cases and sequencing of 179 cases showed that the dominant serotype of DENV shifted from DENV2 in 2017 and 2018 to DENV3 in 2019. DENV3 persisted as the only representative serotype until 2022. Co-circulation of clades B and C of the DENV2 cosmopolitan genotype in 2017 was replaced by circulation of clade C alone in 2018 with all clones disappearing thereafter. DENV3 genotype I was first detected in 2017 and was the only genotype in circulation until 2022. We observed a high incidence of severe cases in 2019 when the DENV3 genotype I became the only virus in circulation. Phylogenetic analysis revealed clusters of severe cases in several different subclades of DENV3 genotype I. Thus, these serotype and genotype changes in DENV may explain the large dengue outbreaks and increased severity of the disease in 2019.

FSGS and COVID-19 in Non-African American Patients.

Collapsing Focal Segmental Glomerulosclerosis (FSGS) has been reported relatively frequently in African American (AA) patients with coronavirus disease 2019 (COVID-19), and it is associated almost always with Apolipoprotein L gen 1 (APOL1) high-risk variants. We reviewed the published literature from April 2020 to November 2022 searching for non-African American (non-AA) patients with FSGS associated with COVID-19 (eight White patients, six Hispanic patients, three Asian patients, one Indian patient, and one Asian Indian patient). The following histologic patterns were found: collapsing (n=11), not otherwise specified (n=5), tip (n=2), and perihilar (n=1). Fifteen of the 19 patients had AKI. The APOL1 genotype was reported in only six of the 19 non-AA patients. Three of them (two Hispanic patients and one White patient) with collapsing FSGS had high-risk APOL1 variants. The other three patients (two White patients and one Hispanic patient with the collapsing variant, tip variant, and not otherwise specified) had low-risk APOL1 variants. Among 53 African American patients with collapsing FSGS associated with COVID-19, 48 had high-risk APOL1 variants and five had low-risk APOL1 variants. We conclude that in non-AA patients, FSGS is a rare complication of COVID-19. FSGS associated with COVID-19 can occur rarely with low-risk APOL1 variants in non-AA and AA patients. Non-AA patients reported to be associated with high-risk APOL1 variants possibly reflect inaccuracy of self-reported race with AA admixture because of unknown ancestry. Given the importance of APOL1 in the pathogenesis of FSGS associated with viral infection and to avoid racial bias, it seems appropriate that APOL1 testing be considered in patients with FSGS associated with COVID-19, regardless of self-reported race.

[Rapid detection and genotyping of SARS-CoV-2 Omicron BA.4/5 variants using a RT-PCR and CRISPR-Cas12a-based assay].

OBJECTIVE: To establish a rapid detection and genotyping method for SARS-CoV-2 Omicron BA.4/5 variants using CRISPPR-Cas12a gene editing technology. METHODS: We combined reverse transcription-polymerase chain reaction (RT-PCR) and CRISPR gene editing technology and designed a specific CRISPPR RNA (crRNA) with suboptimal protospacer adjacent motifs (PAM) for rapid detection and genotyping of SARS- CoV-2 Omicron BA.4/5 variants. The performance of this RT- PCR/ CRISPPR-Cas12a assay was evaluated using 43 clinical samples of patients infected by wild-type SARS-CoV-2 and the Alpha, Beta, Delta, Omicron BA. 1 and BA. 4/5 variants and 20 SARS- CoV- 2-negative clinical samples infected with 11 respiratory pathogens. With Sanger sequencing method as the gold standard, the specificity, sensitivity, concordance (Kappa) and area under the ROC curve (AUC) of RT-PCR/CRISPPR-Cas12a assay were calculated. RESULTS: This assay was capable of rapid and specific detection of SARS- CoV-2 Omicron BA.4/5 variant within 30 min with the lowest detection limit of 10 copies/µL, and no cross-reaction was observed in SARS-CoV-2-negative clinical samples infected with 11 common respiratory pathogens. The two Omicron BA.4/5 specific crRNAs (crRNA-1 and crRNA-2) allowed the assay to accurately distinguish Omicron BA.4/5 from BA.1 sublineage and other major SARS-CoV-2 variants of concern. For detection of SARS-CoV-2 Omicron BA.4/5 variants, the sensitivity of the established assay using crRNA-1 and crRNA-2 was 97.83% and 100% with specificity of 100% and AUC of 0.998 and 1.000, respectively, and their concordance rate with Sanger sequencing method was 92.83% and 96.41%, respectively. CONCLUSION: By combining RT-PCR and CRISPPR-Cas12a gene editing technology, we successfully developed a new method for rapid detection and identification of SARS-CoV-2 Omicron BA.4/5 variants with a high sensitivity, specificity and reproducibility, which allows rapid detection and genotyping of SARS- CoV-2 variants and monitoring of the emerging variants and their dissemination.

HPV prevalence and genotype distribution among women in eastern China during the Covid-19 pandemic.

Since March 2020, the pandemic caused by SARS-CoV-2 has affected nearly all aspects of daily life. In this study, we investigated the age-stratified prevalence and genotype distribution of human papillomavirus (HPV) among females in Shandong province (eastern China) and aimed to provide guidance on HPV-based cervical cancer screening and vaccination. The distribution of HPV genotypes was analyzed using PCR-Reverse Dot Hybridization. The overall infection rate of HPV was 16.4%, which was dominated by high-risk genotypes. The most prevalent genotype was HPV16 (2.9%), followed by HPV52 (2.3%), HPV53 (1.8%), HPV58 (1.5%), and HPV51 (1.3%). Among the positive cases with HPV infection, single-genotype infection was significantly higher than that of multi-genotype infection. In subgroup analyses by age (≤25, 26-35, 36-45, 46-55, >55), HPV16, 52, and 53 were consistently the three most common hrHPV genotypes in all age groups. The infection rate of multi-genotypes in the ≤25 and >55 age groups was significantly higher than that in other age groups. A bimodal distribution of HPV infection rate was observed in different age groups. Among lrHPV genotypes, HPV6, HPV11, and HPV81 were the three most common types in the ≤25 age group, while in other age groups, HPV81, HPV42, and HPV43 are the three most common lrHPV genotypes. This study provides basic information on the distribution and genotypes of HPV in the female population in eastern China, which could improve the application of HPV diagnostic probes and vaccines.

Rapid genotyping of porcine reproductive and respiratory syndrome virus (PRRSV) using MinION nanopore sequencing.

The global distribution and constant evolution are challenges for the control of porcine reproductive and respiratory syndrome virus (PRRSV), one of the most important viruses affecting swine worldwide. Effective control of PRRSV benefits from genotyping, which currently relies on Sanger sequencing. Here we developed and optimized procedures for real-time genotyping and whole genome sequencing of PRRSV directly from clinical samples based on targeted amplicon- and long amplicon tiling sequencing using the MinION Oxford Nanopore platform. Procedures were developed and tested on 154 clinical samples (including lung, serum, oral fluid and processing fluid) with RT-PCR Ct values ranging from 15 to 35. The targeted amplicon sequencing (TAS) approach was developed to obtain sequences of the complete ORF5 (main target gene for PRRSV genotyping) and partial ORF4 and ORF6 sequences of both PRRSV-1 and PRRSV-2 species. After only 5 min of sequencing, PRRSV consensus sequences with identities to reference sequences above 99% were obtained, enabling rapid identification and genotyping of clinical PRRSV samples into lineages 1, 5 and 8. The long amplicon tiling sequencing (LATS) approach targets type 2 PRRSV, the most prevalent viral species in the U.S. and China. Complete PRRSV genomes were obtained within the first hour of sequencing for samples with Ct values below 24.9. Ninety-two whole genome sequences were obtained using the LATS procedure. Fifty out of 60 sera (83.3%) and 18 out of 20 lung samples (90%) had at least 80% of genome covered at a minimum of 20X sequence depth per position. The procedures developed and optimized in this study here are valuable tools with potential for field application during PRRSV elimination programs.

Interferon-Induced Transmembrane Protein 3 rs34481144 C/T Genotype and Clinical Parameters Related to Progression of COVID-19.

Recent research has associated the interferon-induced transmembrane protein 3 gene (IFITM3) with the outcomes of coronavirus disease 2019 (COVID-19), although the findings are contradictory. This study aimed to determine the relationship between IFITM3 gene rs34481144 polymorphism and clinical parameters with COVID-19 mortality. The tetra-primer amplification refractory mutation system-polymerase chain reaction assay was used to analyze IFITM3 rs34481144 polymorphism in 1,149 deceased and 1,342 recovered patients. The clinical parameters were extracted from the patients' medical records. In this study, the frequency of IFITM3 rs34481144 CT genotypes (OR 1.47, 95% CI 1.23-1.76, P < 0.0001) in both sexes was significantly higher in deceased patients than in recovered patients. Moreover, IFITM3 rs34481144 TT genotypes (OR 3.38, 95% CI 1.05-10.87, P < 0.0001) in women were significantly associated with COVID-19 mortality. The multivariable logistic regression model results indicated that mean age (P < 0.001), alkaline phosphatase (P = 0.005), alanine aminotransferase (P < 0.001), low-density lipoprotein (P < 0.001), high-density lipoprotein (P < 0.001), fasting blood glucose (P = 0.010), creatinine (P < 0.001), uric acid (P < 0.001), C-reactive protein (P = 0.004), 25-hydroxyvitamin D (P < 0.001), erythrocyte sedimentation rate (P < 0.001), and real-time PCR Ct values (P < 0.001) were linked with increased COVID-19 death rates. In conclusion, IFITM3 rs34481144 gene polymorphism was linked to the mortality of COVID-19, with the rs34481144-T allele being especially important for mortality. Further studies are needed to confirm the results of this study.

Impact of the COVID-19 restrictions on the epidemiology of Cryptosporidium spp. in England and Wales, 2015-2021: a time series analysis.

Introduction. In England and Wales, cryptosporidiosis cases peak in spring and autumn, associated with zoonotic/environmental exposures (Cryptosporidium parvum, spring/autumn) and overseas travel/water-based activities (Cryptosporidium hominis, autumn). Coronavirus disease 2019 (COVID-19) restrictions prevented social mixing, overseas travel and access to venues (swimming pools/restaurants) for many months, potentially increasing environmental exposures as people sought alternative countryside activities.Hypothesis. COVID-19 restrictions reduced incidence of C. hominis cases and potentially increased incidence of C. parvum cases.Aim. To inform/strengthen surveillance programmes, we investigated the impact of COVID-19 restrictions on the epidemiology of C. hominis and C. parvum cases.Methodology. Cases were extracted from the Cryptosporidium Reference Unit (CRU) database (1 January 2015 to 31 December 2021). We defined two periods for pre- and post-COVID-19 restrictions implementation, corresponding to before and after the first UK-wide lockdown on 23 March 2020. We conducted a time series analysis, assessing differences in C. parvum and C. hominis incidence, trends and periodicity between these periods.Results. There were 21 304 cases (C. parvum=12 246; C. hominis=9058). Post-restrictions implementation incidence of C. hominis dropped by 97.5 % (95 % CI: 95.4-98.6 %; P<0.001). The decreasing incidence trend pre-restrictions was not observed post-restrictions implementation due to lack of cases. No periodicity change was observed post-restrictions implementation. There was a strong social gradient; there was a higher proportion of cases in deprived areas. For C. parvum, post-restrictions implementation incidence fell by 49.0 % (95 % CI: 38.4-58.3 %; P<0.001). There was no pre-restrictions incidence trend but an increasing incidence trend post-restrictions implementation. A periodicity change was observed post-restriction implementation, peaking 1 week earlier in spring and 2 weeks later in autumn. The social gradient was the inverse of that for C. hominis. Where recorded, 22 % of C. hominis and 8 % of C. parvum cases had travelled abroad.Conclusion. C. hominis cases almost entirely ceased post-restrictions implementation, reinforcing that foreign travel seeds infections. C. parvum incidence fell sharply but recovered post-restrictions implementation, consistent with relaxation of restrictions. Future exceedance reporting for C. hominis should exclude the post-restriction implementation period but retain it for C. parvum (except the first 6 weeks post-restrictions implementation). Infection prevention and control advice should be improved for people with gastrointestinal illness (GI) symptoms to ensure hand hygiene and swimming pool avoidance.

Insights and progress on epidemic characteristics, genotyping, and preventive measures of PEDV in China: A review.

Porcine Epidemic Diarrhoea (PED) is an acute, extremely infectious intestinal disease of pigs caused by the Porcine Epidemic Diarrhoea Virus (PEDV). The virus can affect pigs of all breeds and age groups and shows varying degrees of symptoms, with piglets, in particular, being infected with mortality rates of up to 100%. PEDV was first identified in China in the 1980s and in October 2010 a large-scale PED outbreak caused by a variant of PEDV occurred in China, resulting in huge economic losses. Initially, vaccination can effectively prevent the classical strain, but since December 2010, the PEDV variant has caused "persistent diarrhoea" with severe vomiting, watery diarrhoea, and high morbidity and mortality in newborn piglets as the dominant clinical features, with a significant increase in morbidity and mortality. This indicates that PEDV strains have mutated during evolution and that traditional vaccines no longer provide effective cross-immune protection, so it is necessary to optimize immunization programs and find effective treatments through epidemiological surveys of PEDV to reduce the economic losses caused by infections with mutated strains. This article reviews the progress of research on the aetiology, epidemiological characteristics, genotyping, pathogenesis, transmission routes, and comprehensive control of PEDV infection in China.

Outbreak of human astroviruses 1 and Melbourne 2 in acute gastroenteritis pediatric patients in Japan during the COVID-19 pandemic, 2021.

BACKGROUND: Human astrovirus (HAstV) infection is one of the leading causes of acute gastroenteritis in young children. The present study reports the outbreak of HAstV in children with acute gastroenteritis in Kyoto, Japan, during the COVID-19 pandemic, 2021. METHODS: A total of 61 stool samples were collected from children with acute gastroenteritis who visited a pediatric outpatient clinic in Maizuru city, Kyoto, Japan from July to October, 2021. HAstV was screened by RT-PCR, and the genotypes were identified by nucleotide sequence analysis. RESULTS: Of 61 cases of acute gastroenteritis, 20 were mono-infected with HAstV alone. In addition, mixed infection of HAstV and NoV, and HAstV and RVA were also detected in 15 and 1 cases, respectively. Of 36 HAstV strains detected in this outbreak, 29 and 7 were HAstV1 and MLB2 genotypes, respectively. All HAstV1 strains were closely related to the HAstV1 reported from Thailand and Japan in 2021 and all of them belonged to subgenotype HAstV1a. Among MLB2, they were most closely related to the MLB2 strains reported from China in 2016 and 2018. CONCLUSIONS: After the kindergartens and schools were re-opened at the middle of 2021 in Japan, an outbreak of HAstV was reported. Control measures against the COVID-19 pandemics might affect the spread of diarrheal virus infection. Here we report the outbreak of HAstV1 and MLB2 in Kyoto, Japan, during COVID-19 pandemic in 2021.

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Impact of the MCP-1-2518A>G polymorphism on COVID-19 severity in the Iranian population: A case-control study.

As a result of SARS-CoV-2 infection, the host's immune system is disrupted, and chemokines and cytokines are intensified to eliminate the virus, resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19 have been observed to have elevated levels of MCP-1, a chemokine associated with the severity of the disease. In some diseases, polymorphisms in the regulatory region of the MCP-1 gene correspond to serum levels and disease severity. An attempt was made in this study to assess the relationship between MCP-1 G-2518A and serum MCP-1 levels in Iranian COVID-19 patients and the severity of the disease. In this study, patients were randomly sampled from outpatients on the first day of diagnosis and from inpatients on the first day of their hospitalization. Patients were classified into the outpatient (without symptoms or with mild symptoms) and inpatient (with moderate, severe, and critical symptoms) groups. The serum level of MCP-1 was measured by ELISA and the frequency of MCP-1 G-2518A gene polymorphism genotypes in COVID-19 patients was checked by the RFLP-PCR method. Participants with COVID-19 infection had a higher rate of underlying diseases, such as diabetes, high blood pressure, kidney disease, and cardiovascular disease than the control group (P-value < 0.001). Also, the frequency of these factors in inpatients was significantly higher compared to outpatients (P-value < 0.001). Additionally, the level of MCP-1 in serum was significantly different with an average of 11.90 in comparison to 2.98 in the control group (P-value, 0.05), which is attributed to elevated serum levels among patients in hospitals with an average of 11.72 in comparison to 2.98 in the control group. Compared with outpatients, inpatients had a higher frequency of the G allele of the MCP-1-2518 polymorphism (P-value < 0.05), while a notable difference was observed in the serum level of MCP-1 in COVID-19 patients with the MCP-1-2518 AA genotype in the whole group in comparison to the control group (P-value: 0.024). Totally, the results showed that a high frequency of the G allele is related to hospitalization and poor outcome in COVID-19 cases.

Mannose-binding lectin gene 2 variant DD (rs 5030737) is associated with susceptibility to COVID-19 infection in the urban population of Patna City (India).

The study aimed to measure plasma levels of Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) and their polymorphisms in COVID-19 patients and controls to detect association. As MBL is a protein of immunological importance, it may contribute to the first-line host defence against SARS-CoV-2. MBL initiates the lectin pathway of complement activation with help of MASP-1 and MASP-2. Hence, appropriate serum levels of MBL and MASPs are crucial in getting protection from the disease. The polymorphisms of MBL and MASP genes affect their plasma levels, impacting their protective function and thus may manifest susceptibility, extreme variability in the clinical symptoms and progression of COVID-19 disease. The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively.The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively. Our results indicate that median serum levels of MBL and MASP-2 were significantly low in diseased cases but attained normal levels on recovery. Only genotype DD was found to be associated with COVID-19 cases in the urban population of Patna city.

The emergence, impact, and evolution of human metapneumovirus variants from 2014 to 2021 in Spain.

BACKGROUND: Human metapneumovirus (HMPV) is an important aetiologic agent of respiratory tract infection (RTI). This study aimed to describe the prevalence, genetic diversity, and evolutionary dynamics of HMPV. METHODS: Laboratory-confirmed HMPV were characterised based on partial-coding G gene sequences with MEGA.v6.0. WGS was performed with Illumina, and evolutionary analyses with Datamonkey and Nextstrain. RESULTS: HMPV prevalence was 2.5%, peaking in February-April and with an alternation in the predominance of HMPV-A and -B until the emergence of SARS-CoV-2, not circulating until summer and autumn-winter 2021, with a higher prevalence and with the almost only circulation of A2c111dup. G and SH proteins were the most variable, and 70% of F protein was under negative selection. Mutation rate of HMPV genome was 6.95 × 10-4 substitutions/site/year. CONCLUSION: HMPV showed a significant morbidity until the emergence of SARS-CoV-2 pandemic in 2020, not circulating again until summer and autumn 2021, with a higher prevalence and with almost the only circulation of A2c111dup, probably due to a more efficient immune evasion mechanism. The F protein showed a very conserved nature, supporting the need for steric shielding. The tMRCA showed a recent emergence of the A2c variants carrying duplications, supporting the importance of virological surveillance.

Recombinant human adenovirus type 5 based vaccine candidates against GIIa- and GIIb-genotype porcine epidemic diarrhea virus induce robust humoral and cellular response in mice.

Porcine epidemic diarrhea virus (PEDV) is a porcine enteropathogenic coronavirus causing severe watery diarrhea, vomiting, dehydration, and death in piglets. However, most commercial vaccines are developed based on the GI genotype strains, and have poor immune protection against the currently dominant GII genotype strains. Therefore, four novel replication-deficient human adenovirus 5-vectored vaccines expressing codon-optimized forms of the GIIa and GIIb strain spike and S1 glycoproteins were constructed, and their immunogenicity was evaluated in mice by intramuscular (IM) injection. All the recombinant adenoviruses generated robust immune responses, and the immunogenicity of recombinant adenoviruses against the GIIa strain was stronger than that of recombinant adenoviruses against the GIIb strain. Moreover, Ad-XT-tPA-Sopt-vaccinated mice elicited optimal immune effects. In contrast, mice immunized with Ad-XT-tPA-Sopt by oral gavage did not induce strong immune responses. Overall, IM administration of Ad-XT-tPA-Sopt is a promising strategy against PEDV, and this study provides useful information for developing viral vector-based vaccines.