Shift in Demographic Involvement and Clinical Characteristics of COVID-19 From Wild-Type SARS-CoV-2 to the Delta Variant in the Indian Population: In Silico Analysis.

BACKGROUND: The Delta variant (B.1.617.2) was considered the most dangerous SARS-CoV-2 strain; however, in-depth studies on its impact based on demographic and clinical characteristics of COVID-19 are scarce. OBJECTIVE: We aimed to investigate the shift in demographic and clinical characteristics of the COVID-19 pandemic with the emergence of the SARS-CoV-2 Delta variant compared with the wild-type (WT) strain (B.1). METHODS: A cross-sectional study of COVID-19 cases in the Indian population caused by the WT strain (B.1) and Delta variant of SARS-CoV-2 was performed. The viral genomic sequence metadata containing demographic, vaccination, and patient status details (N=9500, NDelta=6238, NWT=3262) were statistically analyzed. RESULTS: With the Delta variant, in comparison with the WT strain, a higher proportion of young individuals (<20 years) were infected (0-9 years: Delta: 281/6238, 4.5% vs B.1: 75/3262, 2.3%; 10-19 years: Delta: 562/6238, 9% vs B.1: 229/3262, 7%; P<.001). The proportion of women contracting infection increased (Delta: 2557/6238, 41% vs B.1: 1174/3262, 36%; P<.001). However, it decreased for men (Delta: 3681/6238, 59% vs B.1: 2088/3262, 64%; P<.001). An increased proportion of the young population developed symptomatic illness and were hospitalized (Delta: 27/262, 10.3% vs B.1: 5/130, 3.8%; P=.02). Moreover, an increased proportion of the women (albeit not men) from the young (Delta: 37/262, 14.1% vs B.1: 4/130, 3.1%; P<.001) and adult (Delta: 197/262, 75.2% vs B.1: 72/130, 55.4%; P<.001) groups developed symptomatic illness and were hospitalized. The mean age of men and women who contracted infection (Delta: men=37.9, SD 17.2 years; women=36.6, SD 17.6 years; P<.001; B.1: men=39.6, SD 16.9 years; women=40.1, SD 17.4 years; P<.001) as well as developing symptoms or being hospitalized (Delta: men=39.6, SD 17.4 years; women=35.6, SD 16.9 years, P<.001; B.1: men=47, SD 18 years; women=49.5, SD 20.9 years, P<.001) were considerably lower with the Delta variant than the B.1 strain. The total mortality was about 1.8 times higher with the Delta variant than with the WT strain. With the Delta variant, compared with B.1, mortality decreased for men (Delta: 58/85, 68% vs B.1: 15/20, 75%; P<.001); in contrast, it increased for women (Delta: 27/85, 32% vs B.1: 5/20, 25%; P<.001). The odds of death increased with age, irrespective of sex (odds ratio 3.034, 95% CI 1.7-5.2, P<.001). Frequent postvaccination infections (24/6238) occurred with the Delta variant following complete doses. CONCLUSIONS: The increased involvement of young people and women, the lower mean age for illness, higher mortality, and frequent postvaccination infections were significant epidemiological concerns with the Delta variant.

Anatomical correlates for the newly discovered meningeal layer in the existing literature: A systematic review.

The existence of a previously unrecognized subarachnoid lymphatic-like membrane (SLYM) was reported in a recent study. SLYM is described as an intermediate leptomeningeal layer between the arachnoid and pia mater in mouse and human brains, which divides the subarachnoid space (SAS) into two functional compartments. Being a macroscopic structure, having missed detection in previous studies is surprising. We systematically reviewed the published reports in animals and humans to explore whether prior descriptions of this meningeal layer were reported in some way. A comprehensive search was conducted in PubMed/Medline, EMBASE, Google Scholar, Science Direct, and Web of Science databases using combinations of MeSH terms and keywords with Boolean operators from inception until 31 December 2023. We found at least eight studies that provided structural evidence of an intermediate leptomeningeal layer in the brain or spinal cord. However, unequivocal descriptions for this layer all along the central nervous system were scarce. Obscure names like the epipial, intermediate meningeal, outer pial layers, or intermediate lamella were used to describe it. Its microscopic/ultrastructural details closely resemble the recently reported SLYM. We further examined the counterarguments in current literature that are skeptical of the existence of this layer. The potential physiological and clinical implications of this new meningeal layer are significant, underscoring the urgent need for further exploration of its structural and functional details.

Sharing of proximal fibers by the anterolateral and lateral collateral ligaments in the human knee: a cadaveric study.

Literature is highly inconsistent in describing the proximal attachment of the anterolateral ligament (ALL) and its relationship with the lateral collateral ligament (LCL) in human knees. This observational study aims to investigate that lacuna. The gross dissection was performed in the lower limbs (n = 83) from the donated adult-age (> 18 years) embalmed cadavers from medical institutions in the north and east India. The dissected knee specimens were first examined macroscopically. Further routine and special staining and microscopic examinations were performed. The ALL was absent in approximately 20.4% of the studied knee specimens (17/83). In remaining, the sharing of ALL and LCL proximal fibers was observed as a consistent finding (~ 97%) with rare exceptions. The mean length of the tibial and meniscal limbs of ALL was 1.57 ± 0.8 cm [Range (R) 0.5-4 cm] and 0.73 ± 0.47 cm [Range (R) 0.1-1.6 cm], respectively. In addition, multiple variations in its presentation were observed. We propose that the proximal sharing of LCL-ALL fibers is a dominant feature in the studied population. The sharing of the fibers may impact the biomechanics and injury mechanisms for both ligaments. The possibility of ethnic variations in the ALL morphology should be a concern during reconstruction surgery.

SARS-CoV-2 Omicron Variant Genomic Sequences and Their Epidemiological Correlates Regarding the End of the Pandemic: In Silico Analysis.

Background: Emergence of the new SARS-CoV-2 variant B.1.1.529 worried health policy makers worldwide due to a large number of mutations in its genomic sequence, especially in the spike protein region. The World Health Organization (WHO) designated this variant as a global variant of concern (VOC), which was named "Omicron." Following Omicron's emergence, a surge of new COVID-19 cases was reported globally, primarily in South Africa. Objective: The aim of this study was to understand whether Omicron had an epidemiological advantage over existing variants. Methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on the Global Initiative on Sharing Avian Influenza Data (GISAID) database to analyze the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period from October 1 to November 29, 2021) with matched epidemiological data (new COVID-19 cases and deaths) from South Africa. Results: Compared with the current list of global VOCs/variants of interest (VOIs), as per the WHO, Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with the Alpha variant for the complete sequence and the RBM. The mutations were found to be primarily condensed in the spike region (n=28-48) of the virus. Further mutational analysis showed enrichment for the mutations decreasing binding affinity to angiotensin-converting enzyme 2 receptor and receptor-binding domain protein expression, and for increasing the propensity of immune escape. An inverse correlation of Omicron with the Delta variant was noted (r=-0.99, P<.001; 95% CI -0.99 to -0.97) in the sequences reported from South Africa postemergence of the new variant, subsequently showing a decrease. There was a steep rise in new COVID-19 cases in parallel with the increase in the proportion of Omicron isolates since the report of the first case (74%-100%). By contrast, the incidence of new deaths did not increase (r=-0.04, P>.05; 95% CI -0.52 to 0.58). Conclusions: In silico analysis of viral genomic sequences suggests that the Omicron variant has more remarkable immune-escape ability than existing VOCs/VOIs, including Delta, but reduced virulence/lethality than other reported variants. The higher power for immune escape for Omicron was a likely reason for the resurgence in COVID-19 cases and its rapid rise as the globally dominant strain. Being more infectious but less lethal than the existing variants, Omicron could have plausibly led to widespread unnoticed new, repeated, and vaccine breakthrough infections, raising the population-level immunity barrier against the emergence of new lethal variants. The Omicron variant could have thus paved the way for the end of the pandemic.

COVID-19 vaccination may enhance hippocampal neurogenesis in adults.

Emerging evidence suggests a detrimental impact of COVID-19 illness on the continued hippocampal neurogenesis in adults. In contrast, the existing literature supports an enhancing effect of COVID-19 vaccination on adult hippocampal neurogenesis. Vaccines against respiratory infections, including influenza, have been shown to enhance hippocampal neurogenesis in adult-age animals. We propose that a similar benefit may happen in COVID-19 vaccinated adults. The vaccine-induced enhancement of the hippocampal neurogenesis in adults thus may protect against age-related cognitive decline and mental disorders. It alsohints at an added mental health benefit of the COVID-19 vaccination programs in adults.

A Bioinformatics Tool for Predicting Future COVID-19 Waves Based on a Retrospective Analysis of the Second Wave in India: Model Development Study.

Background: Since the start of the COVID-19 pandemic, health policymakers globally have been attempting to predict an impending wave of COVID-19. India experienced a devastating second wave of COVID-19 in the late first week of May 2021. We retrospectively analyzed the viral genomic sequences and epidemiological data reflecting the emergence and spread of the second wave of COVID-19 in India to construct a prediction model. Objective: We aimed to develop a bioinformatics tool that can predict an impending COVID-19 wave. Methods: We analyzed the time series distribution of genomic sequence data for SARS-CoV-2 and correlated it with epidemiological data for new cases and deaths for the corresponding period of the second wave. In addition, we analyzed the phylodynamics of circulating SARS-CoV-2 variants in the Indian population during the study period. Results: Our prediction analysis showed that the first signs of the arrival of the second wave could be seen by the end of January 2021, about 2 months before its peak in May 2021. By the end of March 2021, it was distinct. B.1.617 lineage variants powered the wave, most notably B.1.617.2 (Delta variant). Conclusions: Based on the observations of this study, we propose that genomic surveillance of SARS-CoV-2 variants, complemented with epidemiological data, can be a promising tool to predict impending COVID-19 waves.

Can lubrication of the eyelid speculum reduce overall pain perception associated with cataract surgery by phacoemulsification performed under topical anesthesia?

Purpose: This study aimed to evaluate the effect of using the lubricated eyelid speculum on the overall pain perception by the subject patients who underwent cataract surgery by phacoemulsification technique under topical anesthesia. Methods: A prospective interventional randomized comparative study was conducted at the tertiary eye care center, wherein adult patients scheduled for bilateral cataract surgery with phacoemulsification techniques under topical anesthesia were randomized to undergo surgery with two different modes of eyelid speculum insertion, either with or without lubrication of the eyelid speculum. Fifty percent of the patients underwent surgery with eyelid speculum without lubrication, and 50% with lubrication of the eyelid speculum. The primary outcome was to compare the level of overall pain perception among the subject patients of the two groups by using the Visual Analogue Scale (VAS) in the immediate postoperative period. Results: The study included 130 patients who underwent bilateral cataract surgery (n = 260 eyes) under topical anesthesia, wherein n = 130 eyes underwent surgery using lubricated eyelid speculum and n = 130 eyes underwent surgery with dry eyelid speculum. Pain perception score assessed on the VAS (0-10 cm) ranged from 0.5 to 6, with a mean ± standard deviation of 2.06 ± 1.12. A significant correlation was found with two different methods of eyelid speculum insertion with reduced overall pain perception in patients with the use of lubricated eyelid speculum compared to the dry eyelid speculum (P = 0.0001). Conclusion: The overall pain perception associated with cataract surgery performed by phacoemulsification technique under topical anesthesia can be further minimized by lubricating the eyelid speculum prior to insertion for exposing the globe.

Emerging SARS-CoV-2 variants can potentially break set epidemiological barriers in COVID-19.

Young age, female sex, absence of comorbidities, and prior infection or vaccination are known epidemiological barriers for contracting the new infection and/or increased disease severity. Demographic trends from the recent coronavirus disease 2019 waves, which are believed to be driven by newer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, indicate that the aforementioned epidemiological barriers are being breached and a larger number of younger and healthy individuals are developing severe disease. The new SARS-CoV-2 variants have key mutations that can induce significant changes in the virus-host interactions. Recent studies report that, some of these mutations, singly or in a group, enhance key mechanisms, such as binding of the receptor-binding domain (RBD) of the viral spike protein with the angiotensin-converting enzyme 2 (ACE2) receptor in the host-cells, increase the glycosylation of spike protein at the antigenic sites, and enhance the proteolytic cleavage of the spike protein, thus leading to improved host-cell entry and the replication of the virus. The putative changes in the virus-host interactions imparted by the mutations in the RBD sequence can potentially be the reason behind the breach of the observed epidemiological barriers. Susceptibility for contracting SARS-CoV-2 infection and the disease outcomes are known to be influenced by host-cell expressions of ACE2 and other proteases. The new variants can act more efficiently, and even with the lesser availability of the viral entry-receptor and the associated proteases, can have more efficient host-cell entry and greater replication resulting in high viral loads and prolonged viral shedding, widespread tissue-injury, and severe inflammation leading to increased transmissibility and lethality. Furthermore, the accumulating evidence shows that multiple new variants have reduced neutralization by both, natural and vaccine-acquired antibodies, indicating that repeated and vaccine breakthrough infections may arise as serious health concerns in the ongoing pandemic.