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BackgroundFollowing the launch of the global COVID-19 vaccination campaign, there have been increased reports of autoimmune diseases developing de novo following vaccination. These cases include rheumatoid arthritis, autoimmune hepatitis, immune thrombotic thrombocytopenia, and connective tissue diseases. Nevertheless, COVID-19 vaccines are considered safe for patients with autoimmune diseases and are strongly recommended.ObjectivesThe aim of this in silico analysis is to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most commonly administered COVID-19 vaccines, that could elicit an aberrant adaptive immune response in predisposed individuals.MethodsThe FASTA sequence of the protein encoded by the BNT-162b2 vaccine was retrieved from http://genome.ucsc.edu and used as a key input to the Immune Epitope Database and Analysis Resource (www.iedb.org). Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC ligand assays without MHC restriction were searched and evaluated. HLA-disease associations were screened on the HLA-SPREAD platform (https://hla-spread.igib.res.in) by selecting only positive markers.ResultsA total of 183 epitopes were found, corresponding to 178 SARS-CoV-2 and 5 SARS-CoV spike epitopes, respectively. Results were obtained from 22 T-cell assays, 398 B-cell assays, and 2 MHC ligand assays. Complementary receptors included 1080 T-cell receptors and 0 B-cell receptors.Specifically, the IEDB_epitope:1329790 (NATNVVIKVCEFQFCNDPFLGVYY) was shown to bind to HLA-DRB1*15:02 and HLA-DRB1*15:03 alleles, whereas the IEDB_epitope:1392457 (TKCTLKSFTVEKGIYQTSNFRVQPT) was reported to bind to HLA-DRB1*07:01, HLA-DRB1*03:01, HLA-DRB3*01:01, and HLA-DRB4*01:01 alleles. The HLA alleles detected were found to be positively associated with various immunological disorders (Table 1).Table 1.MHC-restricted epitopes of the BNT-162b2 vaccine and potentially associated immunological conditionsEpitopeAssayMHC moleculeAssociated disease (population)NATNVVIKVCEFQFCNDPFLGVYY + OX(C10)cellular MHC/mass spectrometry ligand presentationHLA-DRB1*15:02Takayasu arteritis (Japanese) Arthritis (Taiwanese) Scleroderma (Japanese) Colitis (Japanese)HLA-DRB1*15:03Systemic lupus erythematosus (Mexican American)TKCTLKSFTVEKGIYQTSNFRVQPT + SCM(K2)as aboveHLA-DRB1*07:01Allergy, hypersensitivity (Caucasian)HLA-DRB1*03:01Type 1 diabetes (African) Sarcoidosis, good prognosis (Finnish)HLA-DRB3*01:01Graves' disease (Caucasian) Thymoma (Caucasian) Sarcoidosis (Scandinavian) Autoimmune hepatitis (Caucasian)HLA-DRB4*01:01Vitiligo (Saudi Arabian)ConclusionSimilar to the SARS-CoV-2 spike protein, the protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals. Genotyping for HLA alleles may help identify at-risk individuals. However, further research is needed to elucidate the underlying mechanisms and potential clinical implications.References[1]Vita R, Mahajan S, Overton JA et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 2019 Jan 8;47(D1):D339-D343. doi: 10.1093/nar/gky1006.[2]Dholakia D, Kalra A, Misir BR et al. HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed s. BMC Genomics 23, 10 (2022). https://doi.org/10.1186/s12864-021-08239-0[3]Parker R, Partridge T, Wormald C et al. Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells. Cell Rep. 2021 May 25;35(8):109179. doi: 10.1016/j.celrep.2021.109179.[4]Knierman MD, Lannan MB, Spindler LJ et al. The Human Leukocyte Antigen Class II Immunopeptidome of the SARS-CoV-2 Spike Glycoprotein. Cell Rep. 2020 Dec 1;33(9):108454. doi: 10.1016/j.celrep.2020.108454.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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The human leukocyte antigen (HLA) is a critical component of antigen presentation and plays crucial role in conferring differential susceptibility and severity of diseases caused by viruses such as COVID-19. The immunogenetic profile of populations, BCG vaccination status, and a host of lifestyle factors might contribute to the observed variations in mortality rates due to COVID-19. These genetic, epigenetic, and environmental factors could widely influence infection dynamics and immune responses against COVID-19. The aim of this review is to provide an update on HLA association with SARS-CoV-2 infection in global populations and to highlight the possible neurological involvements. We also set out to explore the HLA immunogenetic markers related to COVID‐19 infections that can be used in screening high‐risk individuals for personalized therapies and in community-based vaccine development. © 2023 Elsevier Inc. All rights reserved.
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Objectives Human leukocyte antigens (HLA) are highly diverse transmembrane proteins that present viral peptides to T cells and launch pathogen-specific immune responses. We aim to investigate the correlation between HLA evolutionary divergence (HED), a surrogate for the capacity to present different peptides, and the outcomes of SARS-CoV-2 infection in a cohort from the St. Louis Metropolitan area. Methods We enrolled adult patients with SARS-CoV-2 infection confirmed by RT-PCR who were hospitalized at two tertiary hospitals in St. Louis between March and July 2020. Genomic DNA was extracted from peripheral blood and genotyped by next-generation sequencing (NGS). HLA alleles were assigned based on key-exon sequences (G group) and limited to the 2-field resolution. HED was calculated by Grantham distance, which considers the difference in composition, polarity, and molecular volume between each pair of amino acids from maternal and paternal HLA. The HED score was obtained for HLA class I (HLA-A, -B, and -C) genotypes using the HLAdivR package in R. Clinical data were collected retrospectively from electronic medical records. A poor outcome was defined as an admission to the intensive care unit (ICU), a need for mechanical ventilation, or death. A favorable outcome was defined as the absence of the above poor outcomes. Results A total of 234 patients were enrolled in this study, 96 being females (41%). The median age and BMI were 66 years old and 28.30 kg/m2, respectively. African Americans comprised 71.4% of the cohort. Only 19 patients (8.1%) presented with no comorbidity;the rest had one or more comorbidities, with cardiovascular diseases being the most common. A total of 137 (58.5%) patients had poor outcomes from SARS-CoV-2 infection, while 97 (41.5%) patients had a favorable outcome. We detected a significant association between higher HLA-B HED and favorable outcomes, with each 1-point increase in HLA-B HED associated with 8% increased probability for the composite endpoint (OR 1.08, 95% CI=1.01-1.16, P = 0.04). The HED scores calculated for HLA-A or HLA-C were not significantly different between patients with favorable or poor outcomes. In a multivariate logistic regression analysis, increased HLA-B HED score, younger age, and no comorbidity were independently associated with favorable outcomes (P = 0.02, P = 0.01, and P = 0.05, respectively). Conclusion Our study shows a significant correlation between lower HLA-B HED scores and poor outcomes after SARS-CoV-2 infection. This finding suggests that maximizing the presentation of diverse SARS-CoV-2 peptides by HLA-B alleles may improve the clearance of SARS-CoV-2. Further studies are warranted to understand the functional and mechanistic implications of this finding.
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AimRespiratory failure remains the most common cause of death in Cystic Fibrosis (CF) with chronic/complex infection a significant contributory factor. Infection frequency and associated treatment burden increase the risk drug-resistant organisms;however, stewardship strategies are challenging to translate to CF care.The CFTR modulator Kaftrio® (elexacaftor/tezacaftor/ivacaftor) launched in the UK in August 2020. Initial phase 3 clinical trials1 2 and a subsequent open-label extension study3 demonstrated promising data on health-related quality of life, including reduced pulmonary exacerbation (PEx) rates (63%), hospitalisation (71%) and PEx requiring IV antibiotics (78%). This evaluation aimed to provide a ‘real-world' review of the impact of Kaftrio® on IV antibiotic burden (admission rates, ‘bed-days', bed-day cost, total IV antibiotic use and ‘AWaRE' antibiotic use) in CF patients aged 12–16 years at a single tertiary centre.MethodA single-centre retrospective observational evaluation was conducted. All 12–16 year olds on Kaftrio® were identified using the local CF database. For each patient: month/year Kaftrio® commenced and prior CFTR modulator therapy were determined. Clinical trial patients were excluded. Digital clinical information systems were used to identify ‘chest-related' admissions for IV antibiotics in the 24 months prior to starting Kaftrio® and the treatment period post, up to June 2022. For each admission, drugs, doses administered and ‘IV antibiotic bed-days' were determined. ‘Bed-day' costs were calculated and use of ‘Restricted' or ‘Watch' antibiotics (WHO AWaRE/local Policy) were identified. IV antibiotic burden pre- and post Kaftrio® was evaluated.Results44 admissions in 33 patients were identified prior to Kaftrio®, compared with 13 admissions post-Kaftrio®, demonstrating a 65–70% overall reduction in admissions (PEx: rate 66/100patient/year vs 23/100patient/year). Pre-Kaftrio® 639 ‘bed days'/24 months were directly attributed to delivery of IV antibiotics-a total estimated cost of £383,400 (estimate £600/day/medical bed). From October 2020-June 2022, the number of IV antibiotic ‘bed days' fell to 183. A total reduction of 71%, with an estimated cost saving of £273,600. In the 24 months prior to Kaftrio® a total 2849 doses of IV antibiotics were administered vs 657 doses in the same patient cohort in the period post-Kaftrio® to June 2022, an absolute reduction of 2192 doses (77%). Of the 2849 IV antibiotics pre-Kaftrio® doses, 84% were restricted/watch antibiotics (R=706;W= 1681). Usage dropped by 37.5% and 89% respectively post-Kaftrio®.ConclusionResults suggest Kaftrio® reduces overall IV antibiotic burden in CF patients, providing real-word data supporting the phase 3 study outcomes. Significant reductions in PEx rates, IV antibiotic use, ‘bed days' and associated costs were all observed. Data demonstrated an absolute reduction in the use of ‘AWaRE' antibiotics, although use still accounts for a high overall proportion in this cohort. Results are limited by the data periods. Potential impact of the COVID-19 pandemic on PEx rates (‘shielding' population) should be considered. Nonetheless, the significance of these findings on overall outcomes and stewardship should not be downplayed. Ongoing review, including expanded patient populations (adults;6–11 years) is essential. Further works looking at oral antibiotics use, epidemiology, genotype and previous CFTR treatment would support extended evaluation of the overall impact of Kaftrio® on infection management in CF.ReferencesMiddleton PG, Mall MA, Drevineck P, et al. Elexacaftor-tezacaftor-ivacaftor for Cystic Fibrosis with a single Phe508del Allele. New England Journal of Medicine 2019;381:1809–1819.Southern K, Murphy J, Sinha I, et al. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants. Cochrane Database of Systematic Review 2020;12;1–313.Griese M, Costa, S, Linnemann R, et al. Safety and e ficacy of Elexacaftor/Tezacaftor/Ivacaftor for 24 weeks or longer in people with cystic fibrosis and one or more F598del Allele: Interim Results of an Open-Label Phase 3 Clinical Trial. American Journal of Respiratory and Critical Medicine 2021;203;381–384.
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More than 2 years into the COVID-19 pandemic with more than 6 million death worldwide, a dysregulated immune response to the pathogen associated with super-activation of pro-inflammatory cytokines, which may cause tissue injury, particularly lung tissue, IL-10 levels can impact on the clinical performance of the patients. this search conducted to detect the effect of Interleukin-10 gene polymorphisms on severity and outcome COVID-19 patients. A case - control study design for 120 COVID-19 patients that divided into sever, critical and moderate/mild patients in addition to 60 healthy subjects as control group to compare IL-10 serum level by ELISA technique and IL-10 gene polymorphism by ARMS-PCR assay. The result illustrated that 120 patients with covid-19 disease m classified as Critical cases 33 (27.5%), sever 42 (35%) and Mild/Moderate were 45 (37.5%). IL-10 increased in the serum of Covid-19 pneumonia patient's to (48.76 ± 12.3) pg / ml in compared with healthy controls (5.47±1.33) pg/ml. genotype results revealed that IL-10 gene distribution was GG homozygous (58.3%) higher in Covid-19 patients in compared to healthy controls (21.7)% and G allele was 124 for patient and 42 for healthy, so GG consider risk factor for coronavirus while AA genotype regard protective factor with frequency reach to 12% in patients and 48.3 % in healthy. The genotype distribution for critical/sever revealed the GG was 74.7% while in M/M was 31.1%. In conclusion: a significant association of GG genotype and allele G was observed with severity of COVID-19 infection.
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These proceedings contains 30 articles that covered various topics related to immunology and related fields. The conference papers presented focused on investigating the role of genetics, microbiome, and immunological pathways in disease pathogenesis and treatment. Studies presented at the conference explored the genetic factors associated with obesity in Brazilian children, the role of flavonoids in reprogramming microglia towards a neuroprotective inflammatory profile, the gut microbiome in asthmatic individuals, and the involvement of the MTOR gene and its variants in the severity of COVID-19. Other studies evaluated the immunodiagnostic potential of a protein exclusive to Corynebacterium pseudotuberculosis, genetic markers associated with alcohol dependence and asthma, and the effects of nicotine on glial cells in Parkinson's disease. The conference also presented research on the molecular mechanisms associated with the anti-glioma and immunomodulatory effects of flavonoids, the influence of Trypanosoma cruzi co-infection on the immune response and clinical outcome of patients with cutaneous leishmaniasis, and the association of metalloproteinase gene variants with periodontitis. Furthermore, the papers presented discussed the production of Zika virus singular peptide for the development of serological immunassays, and the role of genetic polymorphisms in the IL1B and IL6 genes in periodontitis. Lastly, the conference included research on the immunological response of broiler chickens fed with diet supplemented with zinc, and the modulatory effects of Agatis flavone on the glial response in an ex vivo model of brain trauma.
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SARS-CoV2 is a single-stranded RNA virus, gaining much attention after it out broke in China in December 2019. The virus rapidly spread to several countries around the world and caused severe respiratory illness to humans. Since the outbreak, researchers around the world have devoted maximum resources and effort to develop a potent vaccine that would offer protection to uninfected individuals against SARS-CoV2. Reverse vaccinology is a relatively new approach that thrives faster in vaccine research. In this study, we constructed Cytotoxic T Lymphocytes (CTL)-based multi-epitope vaccine using hybrid epitope prediction methods. A total of 121 immunogenic CTL epitopes were screened by various sequence-based prediction methods and docked with their respective HLA alleles using the AutoDock Vina v1.1.2. In all, 17 epitopes were selected based on their binding affinity, followed by the construction of multi-epitope vaccine by placing the appropriate linkers between the epitopes and tuberculosis heparin-binding hemagglutinin (HBHA) adjuvant. The final vaccine construct was modeled by the I-TASSER server and the best model was further validated by ERRAT, ProSA, and PROCHECK servers. Furthermore, the molecular interaction of the constructed vaccine with TLR4 was assessed by ClusPro 2.0 and PROtein binDIng enerGY prediction (PRODIGY) server. The immune simulation analysis confirms that the constructed vaccine was capable of inducing long-lasting memory T helper (Th) and CTL responses. Finally, the nucleotide sequence was codon-optimized by the JCAT tool and cloned into the pET21a (+) vector. The current results reveal that the candidate vaccine is capable of provoking robust CTL response against the SARS-CoV2.Communicated by Ramaswamy H. Sarma.
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Introduction: Cell entry of SARS-CoV-2 causes genome-wide disruption of the transcriptional profiles of genes and biological pathways involved in the pathogenesis of COVID-19. Expression allelic imbalance is characterized by a deviation from the Mendelian expected 1:1 expression ratio and is an important source of allele-specific heterogeneity. Expression allelic imbalance can be measured by allele-specific expression analysis (ASE) across heterozygous informative expressed single nucleotide variants (eSNVs). ASE reflects many regulatory biological phenomena that can be assessed by combining genome and transcriptome information. ASE contributes to the interindividual variability associated with the disease. We aim to estimate the transcriptome-wide impact of SARS-CoV-2 infection by analyzing eSNVs. Methods: We compared ASE profiles in the human lung cell lines Calu-3, A459, and H522 before and after infection with SARS-CoV-2 using RNA-Seq experiments. Results: We identified 34 differential ASE (DASE) sites in 13 genes (HLA-A, HLA-B, HLA-C, BRD2, EHD2, GFM2, GSPT1, HAVCR1, MAT2A, NQO2, SUPT6H, TNFRSF11A, UMPS), all of which are enriched in protein binding functions and play a role in COVID-19. Most DASE sites were assigned to the MHC class I locus and were predominantly upregulated upon infection. DASE sites in the MHC class I locus also occur in iPSC-derived airway epithelium basal cells infected with SARS-CoV-2. Using an RNA-Seq haplotype reconstruction approach, we found DASE sites and adjacent eSNVs in phase (i.e., predicted on the same DNA strand), demonstrating differential haplotype expression upon infection. We found a bias towards the expression of the HLA alleles with a higher binding affinity to SARS-CoV-2 epitopes. Discussion: Independent of gene expression compensation, SARS-CoV-2 infection of human lung cell lines induces transcriptional allelic switching at the MHC loci. This suggests a response mechanism to SARS-CoV-2 infection that swaps HLA alleles with poor epitope binding affinity, an expectation supported by publicly available proteome data.
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COVID-19 , Humans , Alleles , Epitopes , Haplotypes , Lung , Methionine Adenosyltransferase , SARS-CoV-2 , Histocompatibility Antigens Class I/geneticsABSTRACT
Background: COVID-19 is a respiratory disease caused by a novel coronavirus called as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Detected for the first time in December 2019 in Wuhan and it has quickly spread all over the world in a couple of months and becoming a world pandemic. Symptoms of the disease and clinical outcomes are very different in infected people. These differences highlight the paramount need to study and understand the human genetic variation that occurring viral infections. Human leukocyte antigen (HLA) is an important component of the viral antigen presentation pathway, and it plays an essential role in conferring differential viral susceptibility and severity of diseases. HLA alleles have been involved in the immune response to viral diseases such as SARS-CoV-2. Main body of the abstract: Herein, we sought to evaluate this hypothesis by summarizing the association between HLA class I and class II alleles with COVID-19 susceptibility and/or severity reported in previous studies among different populations (Chinese, Italian, Iranian, Japanese, Spanish, etc.). The findings of all selected articles showed that several alleles have been found associated with COVID-19 susceptibility and severity. Even results across articles have been inconsistent and, in some cases, conflicting, highlighting that the association between the HLA system and the COVID-19 outcome might be ethnic-dependent, there were some alleles in common between some populations such as HLA-DRB1*15 and HLA-A*30:02. Conclusion: These contradictory findings warrant further large, and reproducible studies to decipher any possible genetic predisposition underlying susceptibility to SARS-COV-2 and disease progression and host immune response.
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Myriad ecological and evolutionary factors can influence whether a particular parasite successfully transmits to a new host during a disease outbreak, with consequences for the structure and diversity of parasite populations. However, even though the diversity and evolution of parasite populations are of clear fundamental and applied importance, we have surprisingly few studies that track how genetic structure of parasites changes during naturally occurring outbreaks in non-human populations. Here, we used population genetic approaches to reveal how genotypes of a bacterial parasite, Pasteuria ramosa, change over time, focusing on how infecting P. ramosa genotypes change during the course of epidemics in Daphnia populations in two lakes. We found evidence for genetic change - and, therefore, evolution - of the parasite during outbreaks. In one lake, P. ramosa genotypes were structured by sampling date; in both lakes, genetic distance between groups of P. ramosa isolates increased with time between sampling. Diversity in parasite populations remained constant over epidemics, although one epidemic (which was large) had low genetic diversity while the other epidemic (which was small) had high genetic diversity. Our findings demonstrate that patterns of parasite evolution differ between outbreaks; future studies exploring the feedbacks among epidemic size, host diversity, and parasite genetic diversity would improve our understanding of parasite dynamics and evolution.
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HLA genes play a pivotal role in the immune response via presenting the pathogen peptides on the cell surface in a host organism. Here, we studied the association of HLA allele variants of class I (loci A, B, C) and class II (loci DRB1, DQB1, DPB1) genes with the outcome of COVID-19 infection. We performed high-resolution sequencing of class HLA I and class II genes based on the sample population of 157 patients who died from COVID-19 and 76 patients who survived despite severe symptoms. The results were further compared with HLA genotype frequencies in the control population represented by 475 people from the Russian population. Although the obtained data revealed no significant differences between the samples at a locus level, they allowed one to uncover a set of notable alleles potentially contributing to the COVID-19 outcome. Our results did not only confirm the previously discovered fatal role of age or association of DRB1*01:01:01G and DRB1*01:02:01G alleles with severe symptoms and survival, but also allowed us to single out the DQB1*05:03:01G allele and B*14:02:01G~C*08:02:01G haplotype, which were associated with survival. Our findings showed that not only separate allele, but also their haplotype, could serve as potential markers of COVID-19 outcome and be used during triage for hospital admission.
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COVID-19 , Histocompatibility Antigens Class II , Histocompatibility Antigens Class I , Humans , Alleles , COVID-19/genetics , COVID-19/mortality , Gene Frequency , Haplotypes , HLA-DRB1 Chains/genetics , Russia/epidemiologyABSTRACT
The Coronavirus disease 19 (COVID-19) pandemic has resulted in considerable mortality and morbidity worldwide since identified in Wuhan in late 2019. It was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), which is a causative agent of human respiratory tract infection. The detailed mechanism of host immune response and pathogenesis to this virus is not fully elucidated. In this review, we recapitulate the characteristics of immune pathogenies of SARS-CoV-2 infection based on the recent studies of SARS-CoV-2 and previous information on MERS-CoV and SARS-CoV infection that may contribute to disease severity and death. The pathogenesis of COVID-19 includes virus entry and replication, cellular and humoral immunity, cytokine storms, and immune evasion. We also discuss the current approved COVID-19 vaccines in Saudi Arabia;Pfizer-BioNTech (BNT162b2), Oxford-AstraZeneca (ChAdOx1 nCoV-19), and Moderna (mRNA-1273). Furthermore, we review the characteristics and the contraindication of vaccines, and the most effective clinical diagnosis for this virus to combat the infection of SARS-CoV-2.
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Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19.
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COVID-19 , Cystic Fibrosis , Humans , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Alleles , Cystic Fibrosis/pathology , COVID-19/genetics , HeterozygoteABSTRACT
Background and Objective: Despite of the COVID-19 pathogenesis and severity of the infection still completely unclear, but the human's genetic variation in gene participate in SARS-COV2 infectivity, inflammation and immunity response might have a great association with severity of clinical out-comes of nCoV-2019 disease. This study evaluates the impact of CD14-159 and IL4 genotypes on the severity of SARS-COV2 infection. Materials and method: This research have been done with one hundred individuals from Al-Qadisiyah governorate in Iraq, whom infected with SARA-COV2. The patients have been divided into three subgroups according to severity of clinical symptoms;mild, moderate and severe groups. RFLP-PCR technique has been worked out to specify genes polymorphisms.
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Human leucocyte antigens (HLAs) are highly polymorphic glycoproteins expressed at the surface of all nucleated cells. It is required for the SARS-CoV-2 peptide antigen presentation to immune cells for their effector response. However, polymorphism in HLA significantly impacts the binding of SARS-CoV-2 antigenic peptide to the HLA pocket and regulates immune activation. In this study, 514 renal transplant recipients (RTRs) were recruited from the outpatient department and categorized either into symptomatic (n = 173) or asymptomatic groups (n = 341) based on Coronavirus disease-19 (COVID-19) symptoms. The anti-SARS-CoV-2 spike protein-specific IgG antibody titer was measured by chemiluminescent microparticle immune-assay methods in 310 RTRs. The HLA details of 514 patients were retrieved from the electronic medical records and analyzed retrospectively. We found that HLA antigen allele A*24 was significantly associated with asymptomatic infection in 22.78%, HLA C*02 in 4.51%, DRB1*12 in 10.85%, and HLA DQA1*02 in 27.74% of RTRs. Whereas HLA A*29 in 3.46%, A*33 in 26.01%, B*13 in 10.40%, DRB1*10 in 4.62%, DRB1*15 in 39.30%, DRB1*30 in 1.15%, and DQA1*60 in 3.57% of RTRs were associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease. The seroconversion rate in asymptomatic patients was 118/137 (86.13%), had a median titer of 647.80 au/ml, compared to symptomatic patients 148/173 (85.54%) with a median titer of 400.00 au/ml, which was not significant between the two groups (P = 0.88 and 0.13). In conclusion, HLA alleles A*24, C*02, DRB1*12, and DQA1*02 were significantly associated with asymptomatic infection, and A*29, A*33, B*13, DRB1*10, DRB*15, and DRB1*30 were significantly associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease.
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COVID-19 has emerged as the most alarming infection of the present time instigated by the virus SARS-CoV-2. In spite of advanced research technologies, the exact pathophysiology and treatment of the condition still need to be explored. However, SARS-CoV-2 has several structural and functional similarities that resemble SARS-CoV and MERS-CoV which may be beneficial in exploring the possible treatment and diagnostic strategies for SARS-CoV-2. This review discusses the pathogen phenotype, genotype, replication, pathophysiology, elicited immune response and emerging variants of SARSCoV-2 and their similarities with other similar viruses. SARS-CoV-2 infection is detected by a number of diagnostics techniques, their advantages and limitations are also discussed in detail. The review also focuses on nanotechnology-based easy and fast detection of SARS-CoV-2 infection. Various pathways which might play a vital role during SARS-CoV-2 infection have been elaborately discussed since immune response plays a major role during viral infections.
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Introduction: Coronavirus disease 2019 (COVID-19) has brought countless infections and deaths worldwide. COVID-19 patients demonstrated a great diversity in clinical manifestation and disease severity, but factors for these diversions are yet to be determined. Genetic variations such as the single nucleotide polymorphisms (SNPs) might be responsible for COVID-19 severity. Methods: Genomic DNA was extracted from the peripheral blood of 215 recovered COVID-19 patients with different disease severities (asymptomatic, mild, and severe). Their personal information such as gender, age, BMI, and comorbidities was recorded. Global Screening Array (GSA) was performed to search for SNPs linked with the COVID-19 severity. Potential SNPs were further genotyped using real-time PCR for validation, and their risk association was assessed. Results: Hypertension and obesity were the most prevalent comorbidities in severe COVID-19 patients. The GSA showed three potential SNPs (rs923147, rs409017, and rs17062791) that were significantly associated with COVID-19 severity. Further analyses on these SNPs revealed that male, older (>60 years), and overweight subjects who carried an A allele in the rs923147 were protective against severe COVID-19. In contrast, male patients who inherited a G allele had an increased risk of severe COVID-19. For the rs409017 SNP, the presence of an A allele significantly increased the risk of subjects developing severe COVID-19. Besides, obese patients who carried a T allele in the rs17062791 SNP had a significantly lower risk of developing mild symptoms. Conclusion: This study suggests SNPs' potential role that is linked with the COVID-19 severity. These data are useful in predicting the disease severity of COVID-19 patients.
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An unusual pneumonia infection, named COVID-19, was reported on December 2019 in China. It was reported to be caused by a novel coronavirus which has infected approximately 220 million people worldwide with a death toll of 4.5 million as of September 2021. This study is focused on finding potential vaccine candidates and designing an in-silico subunit multi-epitope vaccine candidates using a unique computational pipeline, integrating reverse vaccinology, molecular docking and simulation methods. A protein named spike protein of SARS-CoV-2 with the GenBank ID QHD43416.1 was shortlisted as a potential vaccine candidate and was examined for presence of B-cell and T-cell epitopes. We also investigated antigenicity and interaction with distinct polymorphic alleles of the epitopes. High ranking epitopes such as DLCFTNVY (B cell epitope), KIADYNKL (MHC Class-I) and VKNKCVNFN (MHC class-II) were shortlisted for subsequent analysis. Digestion analysis verified the safety and stability of the shortlisted peptides. Docking study reported a strong binding of proposed peptides with HLA-A*02 and HLA-B7 alleles. We used standard methods to construct vaccine model and this construct was evaluated further for its antigenicity, physicochemical properties, 2D and 3D structure prediction and validation. Further, molecular docking followed by molecular dynamics simulation was performed to evaluate the binding affinity and stability of TLR-4 and vaccine complex. Finally, the vaccine construct was reverse transcribed and adapted for E. coli strain K 12 prior to the insertion within the pET-28-a (+) vector for determining translational and microbial expression followed by conservancy analysis. Also, six multi-epitope subunit vaccines were constructed using different strategies containing immunogenic epitopes, appropriate adjuvants and linker sequences. We propose that our vaccine constructs can be used for downstream investigations using in-vitro and in-vivo studies to design effective and safe vaccine against different strains of COVID-19.
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COVID-19 has had severe consequences worldwide. It has been estimated that the contribution of genetic factors to the disease is about 50%. The A16974C polymorphism of the IL-12 p40 gene has been described as being related to resistance or susceptibility to other infectious diseases;therefore, it is likely that it can also be related to COVID-19. The objective of this study was to describe the relationship between the A16974C polymorphism of the IL12 p40 gene with clinical forms of COVID-19 in Cuban patients. The genotypes of the A16974C polymorphism of gene IL-12 p40 were determined through PCR in 102 persons with a COVID-19 epidemiologic discharge from the hospital. In this research, the CC genotype of this polymorphism was found only in symptomatic cases of this disease;since there are signs of relationship between the A16974C polymorphism of the IL12 p40 gene with clinical forms of COVID-19 in the studied Cuban patients, the variations of this polymorphism may be a predisposing risk factor in the development of COVID-19. © 2022 by the authors.
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Objective: To investigate whether lung function was causally associated with risk of fatality of COVID-19 based on a two-sample Mendelian randomization study.