Short Linear Motifs in the Spike Protein of Sars-Cov-2 Vari-Ants Provide Clues Into Immune Hijack and Evasion Mechanisms of Omicron Variant (preprint)

Short Linear Motifs (SLiMs) are short linear sequences that can mediate protein-protein interaction. Mimicking eukaryotic SLiMs to compete with extra or intracellular binding partners or to sequester host proteins is the crucial strategy of viruses to pervert the host system. The evolved proteins in viruses facilitate minimal protein-protein interactions that significantly affect intracellular signaling networks. Unfortunately, very little information about the SARS-CoV-2 SLiMs is known, especially across the SARS-CoV-2 variants. Through ELM database-based sequence analysis of spike protein from all the major SARS-CoV-2 variants, we identified four overriding SLiMs in the SARS-CoV-2 Omicron variant including LIG_TRFH_1, LIG_REV1ctd_RIR_1, LIG_CaM_NSCaTE_8, and MOD_LATS_1. These SLiMs are highly likely to interfere with various immune functions, interact with host intracellular proteins, regulate cellular pathways, and lubricate viral infection and transmission. These cellular interactions possibly serve as potential therapeutic targets for these variants, and this approach can be further exploited to combat emerging SARS-CoV-2 variants.

Genomic and phenotypic characterization of Multisystem Inflammatory Syndrome in Children (MIS-C): a prospective multicenter study from the Middle East (preprint)

Importance: Clinical, genetic and laboratory characteristics of patients with multisystem inflammatory syndrome in children (MISC) in the Middle East have not yet been documented. Objective: To uncover rare genetic variants contributing to MISC in patients of primarily Arab and Asian origin. Design, Setting, and Participants: A prospective multicenter cohort study was conducted between September 2020 and August 2021 in the United Arab Emirates and Jordan. Forty-five patients meeting the case definition of MISC, and a matched control group of twenty-five healthy children with a confirmed severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection status, were recruited. Whole Exome Sequencing (WES) in all 70 participants was performed to identify rare likely deleterious variants in patients with MISC and to correlate genetic findings with the clinical course of illness. Exposures: SARSCoV2. Main Outcomes and Measures: Fever, organ system complications, laboratory biomarkers, WES findings, treatments, and clinical outcomes. Mann Whitney U test was used to assess the association between genetic variations and MISC attributes. Fishers exact test was used to compute the genetic burden in MISC relative to controls. Results: In 45 MISC patients (23 boys [51.1%]; average age, 7 years [range, 2-14 years]), key inflammatory markers were significantly dysregulated in all patients. Mucocutaneous and gastrointestinal manifestations were reported in 80% (95% CI 66% to 89%) while cardiac and neurological findings were reported in 49% (95% CI 35% to 63%) and 31% (95% CI 19.5% to 45.6%) of patients, respectively. Rare, likely deleterious heterozygous variants in immune related genes including TLR3, TLR6, IFNAR2, IL22RA2, IFNB1, and IFNA6, were identified in 19 patients (42.2%, 95% CI 29% to 56.7%), of whom seven had more than one variant. There was significant enrichment of genetic variants in patients relative to the control group (29 versus 3, P

Impact of Social Isolation on Mental Health Amid COVID-19 Pandemic: A Nationwide Survey (preprint)

Background: Although social isolation is known to limit the spread of a pandemic, the impact of mental health for such measures is yet unknown. In this cross-sectional study, we investigated the impact on mental health among different age groups due to social isolation during the ongoing COVID-19 pandemic in Dhaka, Bangladesh. Methods: We conducted a carefully designed cross sectional survey on mental health that was disseminated widely by way of email, personal contact and social media to subjects aged between 11 and >70 years. For our analysis we stratified data into three distinct groups: children/young adults (11-40), middle age (40-60) and older adult age (> 60) groups. 3214 respondents answered the survey. Bonferroni corrected Chi-square tests were used to find significant relationships between the demographic groups and mental health related variables. Results: We observed a high percentage of insomnia (79%) in old age respondants compared to children/young adults (61%) and middle age (66%) groups, suggesting that ‘age’ is significantly associated (p= 3.8 X 10-06; odds ratio (OR) = 2.34) with ‘insomnia’. Respondents who were retired also reported a higher prevalence (73%) of insomnia (p = 2.79 X 10-8) compare to employed individuals. A higher level of mental stress (84%) was observed in middle aged respondents followed by old adult (71%) respondents (p=0.001). Significantly higher rates (p = 5.08 X 10-27; OR = 2.06) of mental stress were detected in people with preexisting comorbidities compared with the healthy group. The old age participants were less familiar with the concept of social isolation and 54% of old age participants had a negative perception towards social isolation compared to children/young adults (12%) and middle-aged (7%) respondents. Conclusion: Our results indicate an association between age and mental stress concomitant on the COVID-19 social isolation policy in Bangladesh. Social isolation increased insomnia and mental stress, particularly in old age and middle age group. Moreover, these older age groups also tended to have a negative perception of the COVID-19 isolation policy. Therefore, providing mental healthcare services and policy related education in developing countries should target these older age groups to ensure maintenance of their mental wellbeing and adherence to safe practice.  

Host transcriptomic profiling of COVID-19 patients with mild, moderate, and severe clinical outcomes (preprint)

Characterizing key molecular and cellular pathways involved in COVID-19 is essential for disease prognosis and management. We perform shotgun transcriptome sequencing of human RNA obtained from nasopharyngeal swabs of patients with COVID-19, and identify a molecular signature associated with disease severity. Specifically, we identify globally dysregulated immune related pathways, such as cytokine-cytokine receptor signaling, complement and coagulation cascades, JAK-STAT, and TGF-{beta} signaling pathways in all, though to a higher extent in patients with severe symptoms. The excessive release of cytokines and chemokines such as CCL2, CCL22, CXCL9 and CXCL12 and certain interferons and interleukins related genes like IFIH1, IFI44, IFIT1 and IL10 were significantly higher in patients with severe clinical presentation compared to mild and moderate presentations. Moreover, early induction of the TGF-{beta} signaling pathway might be the primary cause of pulmonary fibrosis in patients with severe disease. Differential gene expression analysis identified a small set of regulatory genes that might act as strong predictors of patient outcome. Our data suggest that rapid transcriptome analysis of nasopharyngeal swabs can be a powerful approach to quantify host molecular response and may provide valuable insights into COVID-19 pathophysiology.

Whole genome and phylogenetic analysis of SARS-CoV-2 strains from the index and early patients with COVID-19 in Dubai, United Arab Emirates, 29 January to 18 March 2020 (preprint)

International travel played a significant role in the early global spread of SARS-CoV-2. Understanding transmission patterns from different regions of the world will further inform global dynamics of the pandemic. Using data from Dubai in the United Arab Emirates (UAE), a major international travel hub in the Middle East, we establish SARS-CoV-2 full genome sequences from the index and early COVID-19 patients in the UAE. The genome sequences are analyzed in the context of virus introductions, chain of transmissions, and possible links to earlier strains from other regions of the world. Phylogenetic analysis showed multiple spatiotemporal introductions of SARS-CoV-2 into the UAE from Asia, Europe, and the Middle East during the early phase of the pandemic. We also provide evidence for early community-based transmission and catalogue new mutations in SARS-CoV-2 strains in the UAE. Our findings contribute to the understanding of the global transmission network of SARS-CoV-2.

SARS-CoV-2/COVID-19: Viral Genomics, Epidemiology, Vaccines, and Therapeutic Interventions (preprint)

The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress and fatality. At present, the global case fatality rate of COVID-19 laboratory confirmed cases is ~4.7% ranging from ~0.3-0.4% in Chile and Israel to ~10.8% in Italy. To address this global crisis, up-to-date information on the viral genomics and transcriptomics is crucial for understanding the origins and global dispersal of the virus, providing insight into viral pathogenicity, transmission and epidemiology, and enabling strategies for therapeutic interventions, drug discovery and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.