A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.
Long coronavirus disease (COVID) has emerged as a global health issue, affecting a substantial number of people worldwide. However, the underlying mechanisms that contribute to the persistence of symptoms in long COVID remain obscure, impeding the development of effective diagnostic and therapeutic interventions. In this study, we utilized computational methods to examine the gene expression profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their associations with the wide range of symptoms observed in long COVID patients. Using a comprehensive data set comprising over 255 symptoms affecting multiple organ systems, we identified differentially expressed genes and investigated their functional similarity, leading to the identification of key genes with the potential to serve as biomarkers for long COVID. We identified the participation of hub genes associated with G-protein-coupled receptors (GPCRs), which are essential regulators of T-cell immunity and viral infection responses. Among the identified common genes were CTLA4, PTPN22, KIT, KRAS, NF1, RET, and CTNNB1, which play a crucial role in modulating T-cell immunity via GPCR and contribute to a variety of symptoms, including autoimmunity, cardiovascular disorders, dermatological manifestations, gastrointestinal complications, pulmonary impairments, reproductive and genitourinary dysfunctions, and endocrine abnormalities. GPCRs and associated genes are pivotal in immune regulation and cellular functions, and their dysregulation may contribute to the persistent immune responses, chronic inflammation, and tissue abnormalities observed in long COVID. Targeting GPCRs and their associated pathways could offer promising therapeutic strategies to manage symptoms and improve outcomes for those experiencing long COVID. However, the complex mechanisms underlying the condition require continued study to develop effective treatments. Our study has significant implications for understanding the molecular mechanisms underlying long COVID and for identifying potential therapeutic targets. In addition, we have developed a comprehensive website (https://longcovid.omicstutorials.com/) that provides a curated list of biomarker-identified genes and treatment recommendations for each specific disease, thereby facilitating informed clinical decision-making and improved patient management. Our study contributes to the understanding of this debilitating disease, paving the way for improved diagnostic precision, and individualized therapeutic interventions.
Rotavirus is the leading causative viral agent of pediatric acute gastroenteritis globally, infecting mostly children 5 years old and below. Data on rotavirus prevalence in Malaysia is scarce, despite the WHO's recommendation for continuous rotavirus surveillance, and has underestimated the need for national rotavirus vaccination. Characteristics of the current rotavirus strains in Malaysia have to be determined to understand the rotavirus epidemiology and vaccine compatibility. This study sought to determine the genetic relatedness of Sarawak rotavirus strains with global strains and to determine the antigenic coverage and epitope compatibility of Rotarix and RotaTeq vaccines with the Sarawak rotavirus strains via in silico analysis. A total of 89 stool samples were collected from pediatric patients (<5 years old) with acute gastroenteritis at private hospitals in Kuching, Sarawak. Rotavirus was detected using reverse transcription-polymerase chain reaction. Positive amplicons were analyzed using nucleotide sequencing before phylogenetic analyses and assessment of epitope compatibility. Genotyping revealed G1P[8] (1/13; 7.7%), G3P[8] (3/13; 23%), G9P[4] (1/13; 7.7%), and G9P[8] (3/13; 23%), G9P[X] (1/13; 7.7%), GXP[4] (1/13; 7.7%), and GXP[8] (3/13; 23%) in samples. All wild-type Sarawak rotavirus strains, with the exception of G1, showed variations in their phylogenetic and antigenic epitope characteristics.
The coronavirus disease 2019 (COVID-19) pandemic and related public health intervention measures have been reported to have resulted in the reduction of infections caused by influenza viruses and other common respiratory viruses. However, the influence may be varied in areas that have different ecological, economic, and social conditions. This study investigated the changing epidemiology of 8 common respiratory pathogens, including Influenza A (IFVA), Influenza B (IFVB), Respiratory syncytial virus (HRSV), rhinovirus (RV), Human metapneumovirus Adenovirus, Human bocavirus, and Mycoplasma pneumoniae, among hospitalized children during spring and early summer in 2019-2021 in two hospitals in Hainan Island, China, in the COVID-19 pandemic era. The results revealed a significant reduction in the prevalence of IFVA and IFVB in 2020 and 2021 than in 2019, whereas the prevalence of HRSV increased, and it became the dominant viral pathogen in 2021. RV was one of the leading pathogens in the 3 year period, where no significant difference was observed. Phylogenetic analysis revealed close relationships among the circulating respiratory viruses. Large scale studies are needed to study the changing epidemiology of seasonal respiratory viruses to inform responses to future respiratory virus pandemics.
Pteropine orthoreovirus (PRV), an emerging bat-borne virus, has been linked to cases of acute respiratory infections (ARI) in humans. The prevalence, epidemiology and genomic diversity of PRV among ARI of unknown origin were studied. Among 632 urban outpatients tested negative for all known respiratory viruses, 2.2% were PRV-positive. Patients mainly presented with moderate to severe forms of cough, sore throat and muscle ache, but rarely with fever. Phylogenetic analysis revealed that over 90% of patients infected with the Melaka virus (MelV)-like PRV, while one patient infected with the Pulau virus previously found only in fruit bats. Human oral keratinocytes and nasopharyngeal epithelial cells were susceptible to clinical isolates of PRV, including the newly isolated MelV-like 12MYKLU1034. Whole genome sequence of 12MYKLU1034 using Nanopore technique revealed a novel reassortant strain. Evolutionary analysis of the global PRV strains suggests the continuous evolution of PRV through genetic reassortment among PRV strains circulating in human, bats and non-human primate hosts, creating a spectrum of reassortant lineages with complex evolutionary characteristics. In summary, the role of PRV as a common etiologic agent of ARI is evident. Continuous monitoring of PRV prevalence, pathogenicity and diversity among human and animal hosts is important to trace the emergence of novel reassortants.
Liver disease is a growing burden among people living with HIV (PLHIV) in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels > 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10-year follow-up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score > 1.5, fibrosis-4 score > 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow-up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82-8.77, p
The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron's receptor-binding domain (RBD) and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterizing in the RBD, we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and negative electrostatic surface potential human angiotensin-converting enzyme 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild-type (WT). Negative electrostatic potential of N-terminal domain (NTD) of the spike protein value indicates that the Omicron variant binds receptors less efficiently than the WT. Given that at least one receptor is highly expressed in lung and bronchial cells, the electrostatic potential of NTD negative value could be one of the factors contributing to why the Omicron variant is thought to be less harmful to the lower respiratory tract. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, and R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N.
We aimed to perform meta-analyses to summarize the overall effectiveness of the mRNA-1273 vaccine against COVID-19 caused by the Delta variant from real-world studies. A systematic literature search with no language restriction was performed in electronic databases to identify eligible observational studies that reported the effectiveness of the mRNA-1273 vaccine to prevent reverse transcription-polymerase chain reaction (RT-PCR) confirmed COVID-19 caused by Delta variant of SARS-CoV-2 (B.1.617.2). A random-effects meta-analysis model was used to estimate the pooled odds ratio (OR) at a 95% confidence interval (CI), and the vaccine effectiveness was indicated as (pooled OR - 1)/OR. Five studies were included for this systematic review and meta-analysis. The meta-analysis revealed that the administration of mRNA-1273 vaccine protected against RT-PCR confirmed COVID-19 caused by Delta variant ≥21 days post first dose, with pooled vaccine effectiveness of 66% (95% CI: 65%-67%), as well as ≥14 days after the second dose, with pooled vaccine effectiveness of 91% (95% CI: 84%-95%). In conclusion, the mRNA-1273 vaccine offers a substantial protection rate against RT-PCR confirmed COVID-19 caused by the Delta variant upon full vaccination, although with slightly reduced effectiveness relative to other strains of SARS-CoV-2.
The entire world has been suffering from the coronavirus disease 2019 (COVID-19) pandemic since March 11, 2020. More than a year later, the COVID-19 vaccination brought hope to control this viral pandemic. Here, we review the unknowns of the COVID-19 vaccination, such as its longevity, asymptomatic spread, long-term side effects, and its efficacy on immunocompromised patients. In addition, we discuss challenges associated with the COVID-19 vaccination, such as the global access and distribution of vaccine doses, adherence to hygiene guidelines after vaccination, the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, and vaccine resistance. Despite all these challenges and the fact that the end of the COVID-19 pandemic is still unclear, vaccines have brought great hope for the world, with several reports indicating a significant decline in the risk of COVID19-related infection and hospitalizations.
Emerging severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, especially those of concern, may have an impact on the virus's transmissibility and pathogenicity, as well as diagnostic equipment performance and vaccine effectiveness. Even though the SARS-CoV-2 Delta variant (B.1.617.2) emerged during India's second wave of infections, Delta variants have grown dominant internationally and are still evolving. On November 26, 2021, World Health Organization identified the variant B.1.1.529 as a variant of concern, naming it Omicron, based on evidence that Omicron contains numerous mutations that may influence its behavior. However, the mode of transmission and severity of the Omicron variant remains unknown. We used computational studies to examine the Delta and Omicron variants in this study and found that the Omicron variant had a higher affinity for human angiotensin-converting enzyme 2 (ACE2) than the Delta variant due to a significant number of mutations in the SARS-CoV-2 receptor-binding domain (RBD), indicating a higher potential for transmission. Based on docking studies, the Q493R, N501Y, S371L, S373P, S375F, Q498R, and T478K mutations contribute significantly to high binding affinity with human ACE2. In comparison to the Delta variant, both the entire spike protein and the RBD in Omicron include a high proportion of hydrophobic amino acids such as leucine and phenylalanine. These amino acids are located within the protein's core and are required for structural stability. We observed a disorder-order transition in the Omicron variant between spike protein RBD regions 468-473, and it may be significant in the influence of disordered residues/regions on spike protein stability and binding to ACE2. A future study might investigate the epidemiological and biological consequences of the Omicron variant.
Pteropine orthoreovirus (PRV) is an emerging zoonotic respiratory virus that can be transmitted from bats to humans. In Malaysia, aside from PRV2P (Pulau virus) being isolated from Pteropus hypomelanus sampled in Tioman Island, PRV3M (Melaka virus), PRV4K (Kampar virus), and PRV7S (Sikamat virus) were all isolated from samples of patients who reported having a disease spectrum from acute respiratory distress to influenza-like illness and sometimes even with enteric symptoms such as diarrhea and abdominal pain. Screening of sera collected from human volunteers on Tioman Island in 2001-2002 demonstrated that 12.8% (14/109) were positive for PRV2P and PRV3M. Taking all these together, we aim to investigate the serological prevalence of PRV (including PRV4K and PRV7S) among Tioman Island inhabitants again with the assumption that the seroprevalence rate will remain nearly similar to the above reported if human exposure to bats is still happening in the island. Using sera collected from human volunteers on the same island in 2017, we demonstrated seroprevalence of 17.8% (28/157) against PRV2P and PRV3M, respectively. Seropositivity of 11.4% among Tioman Island inhabitants against PRV4K and PRV7S, respectively, was described in this study. In addition, the seroprevalence of 89.5% (17/19), 73.6% (14/19), 63.0% (12/19), and 73.6% (14/19) against PRV2P, PRV3M, PRV4K, and PRV7S, respectively, were observed among pteropid bats in the island. We revealed that the seroprevalence of PRV among island inhabitants remains nearly similar after nearly two decades, suggesting that potential spill-over events in bat-human interface areas in the Tioman Island. We are unclear whether such spillover was directly from bats to humans, as suspected for the PRV3M human cases, or from an intermediate host(s) yet to be identified. There is a high possibility of the viruses circulating among the bats as demonstrated by high seroprevalence against PRV in the bats.
Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March-June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical.
Enterovirus D68 (EV-D68) is an emerging respiratory pathogen since the 2014 outbreak in USA. A low level of virus circulation has been reported in Kuala Lumpur, Malaysia in the past. However, the extent of the infection in Malaysia is not known. In the present study, we determine the seroepidemiology of EV-D68 in Kuala Lumpur, Malaysia before and after the USA outbreak in Aug 2014. A luciferase-based seroneutralization test was developed using a clone-derived prototype Fermon strain carrying a nanoluciferase marker. We screened the neutralization capacity of 450 serum samples from children and adults (1-89 years old) collected between 2013 to 2015. EV-D68 seropositivity increased with age, with children aged 1-3 showing significantly lower seroprevalence compared to adults. Multivariate analysis showed that older age groups 13-49 years (odds ratio [OR] 4.78 [95% CI 2.69-8.49], p<0.0001) and >50 years (OR 3.83 [95% CI 2.19-6.68], p<0.0001) were more likely to be EV-D68 seropositive than children <13 years. Sampling post-Sept 2014 compared to pre-Sept 2014 also predicted seropositivity (OR 1.66 [95% CI 1.04-2.65]). Presence of neutralizing antibodies against EV-D68 in the study population suggests that EV-D68 was circulating prior to 2014. A higher seropositivity post-Sept 2014 suggests that Malaysia also experienced an upsurge in EV-D68 infections after the USA outbreaks in Aug 2014. A low seropositivity rate observed in children, especially those aged 1-3 years old, suggests that they are at risk and should be prioritized for future vaccination. This article is protected by copyright. All rights reserved.