Correction: SARS-CoV-2 Mutations Responsible for Immune Evasion Leading to Breakthrough Infection.

[This corrects the article DOI: 10.7759/cureus.29544.].

Antiviral Activity of Svarnvir-IV Tablet Assayed for Activity Against SARS-CoV-2 In Vitro.

The coronavirus disease (COVID-19), caused by the virus SARS-CoV-2, has become a global pandemic in a very short time span. While several vaccines have been developed in the last year, specific treatments for CoV infection are still being explored. Thus, the situation highlights the need to develop safe and efficacious antiviral therapeutics. Ayurvedic Rasayana therapy has been traditionally used in India for its holistic healing systems and proven history of empirical use. There is emerging evidence that Ayurvedic treatment methodologies and herbal medicines may be effective strategies in combating COVID-19. The present study is aimed at evaluating the antiviral and therapeutic activity of an Ayurvedic herbomineral formulation (Svarnvir-IV tablet, 450 mg) against the SARS-CoV-2 virus in vitro. A cell-based assay was conducted to evaluate the cytotoxicity of the Svarnvir-IV tablets (Aimil Pharmaceuticals, Delhi, India) for the determination of virucidal activity assessment (at 2 hours) and therapeutic activity assessment (at 1 hour, 2 hours, and 4 hours). When incubated with SARS-CoV-2 virus at 0.1 multiplicity of infection (MoI) for two hours, Svarnvir-IV tablet exhibited virucidal activity against SARS-CoV-2 with an EC50 value of 0.0058 mg/ml. It also exhibited therapeutic activity when treated with cells infected with the SARS-CoV-2 virus (0.1 MoI) for 1 hour, 2 hours and 4 hours post-infection, with an EC50 value of 0.094 mg/ml, 0.023 mg/ml, and 0.05 mg/ml, respectively. The original supporting data obtained from this study, along with existing Ayurvedic traditional information, has shown encouraging results.

Anthropometric Analysis of Distal Femur Parameters in the Eastern Uttar-Pradesh Population.

INTRODUCTION: Anthropometric measurements of the distal femoral fragment play a crucial role in prosthesis design during arthroplastic knee surgeries and offer valuable clues for stature estimation in forensic investigations. The present study is an attempt to assess various anthropometric parameters of the distal femur in this regard. MATERIALS AND METHODS: A total of 96 intact dry femora were anthropometrically assessed using digital Vernier calipers. The femoral length was measured using an osteometric table. The torsion angle was calculated with an analog goniometer. The various parameters studied included: medial condyle length and thickness, lateral condyle length and thickness, bicondylar width, intercondylar width, intercondylar depth, torsional angle, and femoral length. The data obtained were statistically analyzed using SPSS software (IBM Corp., Armonk, NY, USA). RESULTS: Mean medial condyle length was 57.38±4.47mm and thickness was 24.53±2.27mm. Mean lateral condyle length and thickness were found to be 58.49±4.3mm and 25.33±3.15mm respectively. Mean bicondylar width was 71.96±6.73mm, mean intercondylar width 21.86±2.71mm, and the intercondylar depth 27.04±2.59mm respectively. The average femur length was 41.87±3.31mm and the average torsion angle was 20.19°±6.99°. Significant correlations were observed between distal femoral parameters. Lateral condyle length showed maximum correlation with other parameters. Femur length was found to correlate significantly with all parameters except medial condyle thickness. Torsion angle was significantly correlated with lateral condyle length and femur length only. DISCUSSION: The findings of this study show considerable variation from those of other studies done within India. This proves that distal femoral anthropometry has regional variations. These data can aid sports physicians and orthopedic surgeons with implant designing and forensic experts during investigations.

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.

Morphometric Analysis of the Proximal Femur With Its Clinical Correlation in Eastern Uttar Pradesh Region.

The anthropometry of the proximal femur holds great clinical significance in designing implants and prostheses for proximal femoral fractures and hip joint arthroplasties. Surgical fixation with a properly matched prosthesis plays a crucial role in improving long-term treatment outcomes and preventing post-operative complications such as osteolysis with aseptic loosening and increased load. The femur is also one of the most commonest used bones for stature estimation. Often during forensic investigations, only fragmented remains of femur are found available from which femoral length is estimated by application of linear regression equations. The estimated femoral length thus obtained is used for stature estimation of the unidentified individual. This study has measured nine bony parameters from the proximal femur in a total of 96 dry femora. These measurements include the vertical head diameter, neck diameter, neck thickness, neck length, neck shaft angle, the transverse diameter of the fovea, longitudinal diameter of the fovea, foveal depth, and the intertrochanteric line length. In addition, the total length of the femur was also measured. The results were tabulated and statistically analyzed using SPSS software, version 25. The mean femoral head diameter was observed to be 41.59±3.25 mm, mean foveal depth was found to be 2.95±0.75 mm, mean foveal transverse and longitudinal diameters were observed to be 11.38±2.35 mm and 15.94±3.37 mm, respectively. The mean neck diameter was 29.45±3.33 mm. Mean neck length and neck thickness were observed to be 36.06±4.94 mm and 27.61±2.71 mm, respectively. Neck shaft angle was noted to range from 109° to 128°, with a mean of 119.08°±5.18°. The mean length of the inter-trochanteric line was measured to be 41.92±3.9 mm. The mean femoral length was observed to be 42.11±2.91 cm. Significant positive correlations were found between the various measured proximal morphometric parameters of the femur. The length of the femur showed a maximum positive correlation with the vertical head diameter, followed by the neck diameter, thickness, and foveal depth. The findings of this study can throw further light on the existing data. They can serve as a guideline for designing better-matched prostheses and implants for hip surgeries in the eastern Uttar Pradesh population.

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.

SARS-CoV-2 Mutations Responsible for Immune Evasion Leading to Breakthrough Infection.

BACKGROUND AND OBJECTIVES: India had faced a devastating second outbreak of COVID-19 infection, in which a majority of the viral sequences were found to be of the B.1.617.2 lineage (Delta-variant). While India and the world focused on vaccination, reports of vaccine-immunity evasion by the virus, termed "breakthrough cases", emerged worldwide. Our study was focused on the primary objective to identify the mutations associated with breakthrough infections SARS-CoV-2. METHODS: In our study, we extracted the SARS-CoV-2 RNA (ribonucleic acid) from reverse transcription-polymerase chain reaction (RT-PCR) positive COVID-19 patients, and 150 random samples were sent for sequencing to the Centre for Cellular & Molecular Biology, Hyderabad. Whole genome sequences of 150 SARS-CoV-2 viral samples were analyzed thoroughly. We mostly found B.1.617 and its sub-lineages in the genomic sequencing results. RESULTS AND INTERPRETATION: On further analysis of patient data, it was seen that nine patients had been vaccinated against the SARS-CoV-2 previously. These nine patients had B.1.617/B.1 or A strains, and all of them had similar genomic variations in spike proteins as well as non-structural proteins (NSPs). The mutations seen in these sequences in the Spike (S), NSPs, and open reading frame (ORF) regions would have produced amino acid changes known to improve viral replication, confer drug resistance, influence host-cell interaction, and lead to antigenic drift. CONCLUSIONS: Increased virulence culminating in vaccine immunity evasion may be inferred from these specific mutations. Our study adds to the growing body of evidence linking rapidly emerging mutations in the S (Spike) and ORF genes of the SARS-CoV-2 genome to immune evasion.

Evaluation of Safety Concerns for COVID-19 Immunization of Pregnant Women: a Systematic Review of Emerging Evidence.

Objectives: There is an urgent need to review the status of COVID-19 vaccine immunization in pregnant women globally, so that adverse outcomes may be prevented. In this study, we performed a systematic review to evaluate the probable outcomes of COVID-19 vaccination in pregnant women. Materials and methods:An electronic search over three months (June 15-August 15, 2021) was conducted. Original studies evaluating safety concerns in pregnant women for COVID-19 vaccination were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines were used for data collection and reporting of findings. Results:COVID-19 vaccination in pregnant women was not associated with increased adverse effects or complications to the mother as well as the developing fetus or new-born compared to non-vaccinated pregnant women. Vaccinated pregnant women showed a robust immune response against COVID-19 infection. Conclusion:COVID-19 vaccination during pregnancy causes no significant health risks for the mother or the developing fetus or new-born.