Rapid COVID-19 diagnosis using ensemble deep transfer learning models from chest radiographic images.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes novel coronavirus disease (COVID-19) outbreak in more than 200 countries around the world. The early diagnosis of infected patients is needed to discontinue this outbreak. The diagnosis of coronavirus infection from radiography images is the fastest method. In this paper, two different ensemble deep transfer learning models have been designed for COVID-19 diagnosis utilizing the chest X-rays. Both models have utilized pre-trained models for better performance. They are able to differentiate COVID-19, viral pneumonia, and bacterial pneumonia. Both models have been developed to improve the generalization capability of the classifier for binary and multi-class problems. The proposed models have been tested on two well-known datasets. Experimental results reveal that the proposed framework outperforms the existing techniques in terms of sensitivity, specificity, and accuracy.

Multiplexed Reverse Transcription Loop-Mediated Isothermal Amplification Coupled with a Nucleic Acid-Based Lateral Flow Dipstick as a Rapid Diagnostic Method to Detect SARS-CoV-2.

Due to the high reproduction rate of COVID-19, it is important to identify and isolate infected patients at the early stages of infection. The limitations of current diagnostic methods are speed, cost, and accuracy. Furthermore, new viral variants have emerged with higher rates of infectivity and mortality, many with mutations at various primer binding sites, which may evade detection via conventional PCR kits. Therefore, a rapid method that is sensitive, specific, and cost-effective is needed for a point-of-care molecular test. Accordingly, we developed a rapid molecular SARS-CoV-2 detection kit with high specificity and sensitivity, RT-PCR, taking advantage of the loop-mediated isothermal amplification (LAMP) technique. Four sets of six primers were designed based on conserved regions of the SARS-CoV-2 genome: two outer, two inner and two loop primers. Using the optimized protocol, SARS-CoV-2 genes were detected as quickly as 10 min but were most sensitive at 30 min, detecting as little as 100 copies of template DNA. We then coupled the RT-LAMP with a lateral flow dipstick (LFD) for multiplex detection. The LFD could detect two genic amplifications on a single strip, making it suitable for multiplexed detection. The development of a multiplexed RT-LAMP-LFD reaction on crude VTM samples would be suitable for the point-of-care diagnosis of COVID-19 in diagnostic laboratories as well as in private homes.

The supply is there. So why can't pregnant and breastfeeding women in rural India get the COVID-19 vaccine?

Despite COVID-19 vaccines being available to pregnant women in India since summer 2021, little is known about vaccine uptake among this high need population. We conducted mixed methods research with pregnant and recently delivered rural women in northern India, consisting of 300 phone surveys and 15 in-depth interviews, in November 2021. Only about a third of respondents were vaccinated, however, about half of unvaccinated respondents reported that they would get vaccinated now if they could. Fears of harm to the unborn baby or young infant were common (22% of unvaccinated women). However, among unvaccinated women who wanted to get vaccinated, the most common barrier reported was that their health care provider refused to provide them the vaccine. Gender barriers and social norms also played a role, with family members restricting women's access. Trust in the health system was high, however, women were most often getting information about COVID-19 vaccines from sources that they did not trust, and they knew they were getting potentially poor-quality information. Qualitative data shed light on the barriers women faced from their family and health care providers but described how as more people got the vaccine that norms were changing. These findings highlight how pregnant women in India have lower vaccination rates than the general population, and while vaccine hesitancy does play a role, structural barriers from the health care system also limit access to vaccines. Interventions must be developed that target household decision-makers and health providers at the community level, and that take advantage of the trust that rural women already have in their health care providers and the government. It is essential to think beyond vaccine hesitancy and think at the system level when addressing this missed opportunity to vaccinate high risk pregnant women in this setting.

Early diagnosis of COVID-19 patients using deep learning-based deep forest model

Coronavirus disease-19 (COVID-19) has rapidly spread all over the world. It is found that the low sensitivity of reverse transcription-polymerase chain reaction (RT-PCR) examinations during the early stage of COVID-19 disease. Thus, efficient models are desirable for early-stage testing of COVID-19 infected patients. Chest X-ray (CXR) images of COVID-19 infected patients have shown some bilateral changes. In this paper, deep transfer learning and a deep forest-based model are proposed to diagnose COVID-19 infection from CXR images. Initially, features of X-ray images are extracted using the well-known deep transfer learning model (i.e., ResNet101), which does not require tuning many parameters compared to the deep convolutional neural network (CNN). After that, the deep forest model is utilised to predict COVID-19 infected patients. The deep forest is based upon ensemble learning and requires a small number of hyper-parameters. Additionally, the proposed model is trained on a multi-class dataset that contains four different classes as COVID-19 (+), pneumonia, tuberculosis, and healthy patients. The comparisons are drawn among the proposed deep transfer learning and deep forest-based models, the competitive models. The obtained results show that the proposed model effectively diagnoses COVID-19 infection with an accuracy of 99.4%.

Comprehensive deep mutational scanning reveals the pH induced stability and binding differences between SARS-CoV-2 spike RBD and human ACE2.

The SARS-CoV-2 spike (S) glycoprotein with its mobile receptor-binding domain (RBD), binds to the human ACE2 receptor and thus facilitates virus entry through low-pH-endosomal pathways. The high degree of SARS-CoV-2 mutability has raised concern among scientists and medical professionals because it created doubt about the effectiveness of drugs and vaccinations designed specifically for COVID-19. In this study, we used computational saturation mutagenesis approach, including structure-based free energy calculations to analyse the effects of the missense mutations on the SARS-CoV-2 S-RBD stability and the S-RBD binding affinity with ACE2 at three different pH (pH 4.5, pH 6.5, and pH 7.4). A total of 3705 mutations in the S-RBD protein were analyzed, and we discovered that most of these mutations destabilize the RBD protein. Specifically, residues G404, G431, G447, A475, and G526 were important for RBD protein stability. In addition, RBD residues Y449, Y489, Y495, Q498, and N487 were critical for the RBD-ACE2 interaction. Next, we found that the distribution of the mean stability changes and mean binding energy changes of RBD due to mutations at both serological and endosomal pH correlated well, indicating the similar effects of mutations. Overall, this computational analysis is useful for understanding the effects of missense mutations in SARS-CoV-2 pathogenesis at different pH.Communicated by Ramaswamy H. Sarma.

Pregnancy Outcomes in Women With SARS-CoV-2 Infection During the First and Second Waves of the COVID-19 Pandemic in a Tertiary Care Hospital in Ayodhya, Uttar Pradesh, India: A Comparative Study.

Introduction Pregnancy is an altered immunological state and not necessarily an immune-compromised state. These immune changes subject pregnant women to increased susceptibility to infection. During the coronavirus disease 2019 (COVID-19) pandemic, pregnant women were more susceptible to serious illness for reasons other than their immune response. The purpose of this study was to compare the feto-maternal outcome (morbidity and mortality) in relation to pre-existing maternal co-morbidities, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-related disease severity, and its impact on the mode of delivery and long-term sequelae in pregnant women in the first and second waves of the COVID-19 pandemic. Materials and methods This was a hospital-based comparative study carried out on 101 pregnant patients during the first wave (April 2020 to December 2020) and 22 patients in the second wave (March 2021 to July 2021) of the COVID-19 pandemic, in Rajashri Dashrath Autonomous State Medical College, Ayodhya, India. All pregnant women with COVID-19 in the first and second waves were included. Non-pregnant patients with COVID-19 infection, pregnant patients lost to follow-up, pregnant patients without COVID-19 infection, and patients in the puerperal period were excluded. Results Seventy-three (72.27%) patients in the first wave and 12 (54.54%) in the second wave were asymptomatic. Those with mild disease numbered 20 (25.74%) in the first wave and six (27.27%) in the second wave. Disease severity was more in the second wave, that is four (18.18%) as compared to one (0.99%) in the first wave. Severe anemia was the most common co-morbidity associated with both first (n=4, 3.96%) and second (n=5, 22.72%) waves. Four (6.45%) spontaneous abortions occurred in the first wave as compared to three (20%) in the second wave. Intensive care unit (ICU) admission was more in the second wave (n=4, 26.66%) as compared to the first wave (n=1, 1.61%). Two (13.33%) maternal deaths occurred in the second wave and none in the first wave. Cesarean sections in both the first and second waves were performed for obstetric indications only. No newborns tested positive in the COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) in the first and second waves at the time of birth; however, three (4.83%) tested positive on day five of birth in the first wave. Fever was the most common presentation in newborns; seven (11.26%) in the first wave and three (20%) in the second wave. No neonatal death occurred in the first or second waves. No congenital anomalies were noted in the first or second waves of COVID-19. Conclusion In this study, we found that the maximum number of COVID-19-positive pregnant patients in both the first and second waves of COVID-19 were either asymptomatic or had mild infections. Second-wave infection was more lethal as compared to the first wave in terms of adverse maternal as well as fetal outcomes. No gestational age was an exception to the severity of disease and its adverse feto-maternal outcome. In our study, maternal co-morbidities did not impact the overall outcome. All cesarean sections were performed for indications other than COVID-19 infection. Long-term sequelae associated with COVID-19 were seen in both groups but more so in the second wave. No long-term sequelae like congenital anomalies in the babies were associated with COVID-19 either in the first or second wave.

Development of the India COVID-19 vaccine tracker.

COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Since then, efforts were initiated to develop safe and effective vaccines. Till date, 11 vaccines have been included in the WHO's emergency use list. The emergence and spread of variant strains of SARS-CoV-2 has altered the disease transmission dynamics, thus creating a need for continuously monitoring the real-world effectiveness of various vaccines and assessing their overall impact on disease control. To achieve this goal, the Indian Council of Medical Research (ICMR) along with the Ministry of Health and Family Welfare, Government of India, took the lead to develop the India COVID-19 Vaccination Tracker by synergizing three different public health databases: National COVID-19 testing database, CoWIN vaccination database and the COVID-19 India portal. A Vaccine Data Analytics Committee (VDAC) was constituted to advise on various modalities of the proposed tracker. The VDAC reviewed the data related to COVID-19 testing, vaccination and patient outcomes available in the three databases and selected relevant data points for inclusion in the tracker, following which databases were integrated, using common identifiers, wherever feasible. Multiple data filters were applied to retrieve information of all individuals ≥18 yr who died after the acquisition of COVID-19 infection with or without vaccination, irrespective of the time between vaccination and test positivity. Vaccine effectiveness (VE) against the reduction of mortality and hospitalizations was initially assessed. As compared to the hospitalization data, mortality reporting was found to be much better in terms of correctness and completeness. Therefore, hospitalization data were not considered for analysis and presentation in the vaccine tracker. The vaccine tracker thus depicts VE against mortality, calculated by a cohort approach using person-time analysis. Incidence of COVID-19 deaths among one- and two-dose vaccine recipients was compared with that among unvaccinated groups, to estimate the rate ratios (RRs). VE was estimated as 96.6 and 97.5 per cent, with one and two doses of the vaccines, respectively, during the period of reporting. The India COVID-19 Vaccination Tracker was officially launched on September 9, 2021. The high VE against mortality, as demonstrated by the tracker, has helped aid in allaying vaccine hesitancy, augmenting and maintaining the momentum of India's COVID-19 vaccination drive.

Experimental investigation on the use of covid-19 waste in bituminous concrete.

The COVID-19 pandemic has resulted in unprecedented growth in the production and disposal of PPEs, face masks, gloves, face shields, and disinfectants. Daily consumption of masks and PPE has increased the plastic load on the municipality and very few plastics are taken to the recycling during the complete shut down during Covid-19. Plastic pollution is already a matter of concern that is increasing due to the negligence of humans. COVID-19 health crisis puts extra pressure on the regular waste management systems as increased daily consumption of single-use plastics around the world. It leads to the inappropriate management of waste; including mobile incineration, direct land-filling, and local burning of the waste. As the PPE kits and gowns are made of polypropylene plastic, they are non-biodegradable like any other plastics. Incineration and land-filling of plastics do not help them to degrade, even if it increases the number of pollutants in the form of microparticles. In this paper, we discussed the research procedures to utilize the waste plastic specifically Covid-19 waste which is received from the health care clinics in Bituminous concrete for the construction of flexible roads. The main objective of the study was to investigate the effectiveness of the bituminous mix modified with Polypropylene gowns waste and to compare it with the conventional bituminous mix. This research concentrated on the Maximum Stability and Flow Value of the asphalt mixture with the waste. The measurements of the Plastic of 10%, 12.5%, 15%, 17.5 %, and 20% were utilized as substitutions for the bitumen binder in the mix. From the experimental investigation, it is concluded that the optimum bitumen content is found at 10% Plastic waste with 6.5 bitumen content. Bitumen properties also increase with the addition of PPE waste. [copyright information to be updated in production process].

The baneful alliance of COVID-19 and mucormycosis: Histopathological concerns.

Background: Mucormycosis, once a rare fungal disease, has now shown a surge in cases, and its epidemiology in India is intriguing. Rising incidence confers the necessity of defining the demography of the population at risk, early diagnosis, and recommendations for the management of mucormycosis in patients with coronavirus disease (COVID-19) infection. Aims: To study the clinico-epidemological profile, risk factors, and histopathological features of COVID-19-associated Mucormycosis (CAM). Setting and Design: This is a retrospective observational study. Material and Methods: Fifty-six biopsy specimens taken from patients of COVID-19 with clinical suspicion of mucormycosis were included. Results: Diabetes mellitus, corticosteroids, and oxygen therapy were the most common risk factors associated with CAM. The mean duration between the onset of symptoms of COVID-19 and onset of CAM was 25.2 ± 15.3 days. Rhino-orbito-cerebral mucormycosis (ROCM) was present in 24.5% of the cases, with a survival rate of 58.3%. Histopathology showed tissue invasion by branching broad-based, pale, fungal hyphae consistent with mucor in 49 (87.5%) cases. Inflammation was acute neutrophilic type in 61.2% of the patients with a survival rate of 63.33%. The survival rate with chronic non-granulomatous and chronic granulomatous was 100% and 81.8%, respectively. Conclusion: Keeping a high index of suspicion for mucormycosis in COVID-19 by all medical fraternities of the health community in the existence of risk factors is the need of the hour for prompt diagnosis. Biopsy of antral necrotic tissue should be performed immediately after suspicion for histopathological study to confirm the diagnosis of mucormycosis and predict prognosis depending on the type of inflammation incited, fungal morphology, load, and necrosis.

Energetic and frustration analysis of SARS-CoV-2 nucleocapsid protein mutations.

The ongoing COVID-19 spreads worldwide with the ability to evolve in diverse human populations. The nucleocapsid (N) protein is one of the mutational hotspots in the SARS-CoV-2 genome. The N protein is an abundant RNA-binding protein critical for viral genome packaging. It comprises two large domains including the N-terminal domain (NTD) and the C-terminal domain (CTD) linked by the centrally located linker region. Mutations in N protein have been reported to increase the severity of disease by modulating viral transmissibility, replication efficiency as well as virulence properties of the virus in different parts of the world. To study the effect of N protein missense mutations on protein stability, function, and pathogenicity, we analyzed 228 mutations from each domain of N protein. Further, we have studied the effect of mutations on local residual frustration changes in N protein. Out of 228 mutations, 11 mutations were predicted to be deleterious and destabilized. Among these mutations, R32C, R191C, and R203 M mutations fall into disordered regions and show significant change in frustration state. Overall, this work reveals that by altering the energetics and residual frustration, N protein mutations might affect the stability, function, and pathogenicity of the SARS-CoV-2.

The supply is there. So why can't pregnant and breastfeeding women in rural India get the COVID-19 vaccine?

Despite COVID-19 vaccines being available to pregnant women in India since summer 2021, little is known about vaccine uptake among this high need population. We conducted mixed methods research with pregnant and recently delivered rural women in northern India, consisting of 300 phone surveys and 15 in-depth interviews, in November 2021. Only about a third of respondents were vaccinated, however, about half of unvaccinated respondents reported that they would get vaccinated now if they could. Fears of harm to the unborn baby or young infant were common (22% of unvaccinated women). However, among unvaccinated women who wanted to get vaccinated, the most common barrier reported was that their health care provider refused to provide them the vaccine. Gender barriers and social norms also played a role, with family members restricting women's access. Trust in the health system was high, however, women were most often getting information about COVID-19 vaccines from sources that they did not trust, and they knew they were getting potentially poor-quality information. Qualitative data shed light on the barriers women faced from their family and health care providers but described how as more people got the vaccine that norms were changing. These findings highlight how pregnant women in India have lower vaccination rates than the general population, and while vaccine hesitancy does play a role, structural barriers from the health care system also limit access to vaccines. Interventions must be developed that target household decision-makers and health providers at the community level, and that take advantage of the trust that rural women already have in their health care providers and the government. It is essential to think beyond vaccine hesitancy and think at the system level when addressing this missed opportunity to vaccinate high risk pregnant women in this setting.

Efficacy of intravenous vitamin C in management of moderate and severe COVID-19: A double blind randomized placebo controlled trial.

Aim: To study the efficacy of intravenous vitamin C in management of moderate and severe COVID-19. Objective: To determine the efficacy of intravenous vitamin C in reducing in-hospital mortality in moderate and severe cases of COVID-19. Design: Parallel, double-blinded randomized controlled trial with placebo. Ethical clearance was obtained from the institutional ethics committee, AIIMS Patna. The trial was registered with the Clinical Trials Registry - India (registration number- CTRI/2020/11/029230.). Setting: A tertiary care centre in Bihar, India. Participants: All patients above the age of 18 years both males and females, admitted in ICU with a diagnosis of moderate and severe COVID-19 (on the basis of a positive reverse transcriptase polymerase chain reaction (RT-PCR) report) at our facility during the study period (01/10/2020-31/12/2020) not having any of the exclusion criteria. Intervention: The patients in the intervention arm were given 1 gram (2 ampoules of 2 ml each containing 500 mg of vitamin C mixed in 100 ml normal saline) intravenous vitamin C 8 hourly for four days. The patients in the placebo arm received similar looking ampoules (2 ampoules of 2 ml sterile water for injection mixed in 100 ml normal saline) intravenously 8 hourly for four days. The rest of the treatment was given as per the standard operating procedure (SOP) of the institute with adjustments as per treating team's judgement. Outcome Measures: Primary outcome was reduction in in-hospital mortality. Secondary outcomes were improvement in qSOFA score, pO2/fiO2 ratio, fall in inflammatory markers, need for mechanical ventilation and vasopressors. Results: Regarding primary outcome, 10 (33.3%) patients died in intervention group compared to 13 (43.3%) in placebo. Worth noting from baseline characteristics is that 86.7% in intervention arm were of severe category compared to 66.7% severe category patients in placebo group. Though number of severe cases were more in intervention arm there has been comparatively less mortality in this group. Regarding secondary outcomes, amongst 30 patients in vitamin C group, 11 (36.7%) required invasive mechanical ventilation compared to 14 (46.7%) out of 30 in placebo group but the difference was not statistically significant. Although there were a greater number of moderate cases in placebo group, invasive ventilation requirement (and NIV requirement) was more in this group, thus it could be considered that vitamin C might have a role in reducing the severity of disease. The need for vasopressor therapy was higher in intervention arm 33.3% compared to 26.7% in placebo but not significant statistically. The secondary outcomes of the study such as improvement in organ failure score (qSOFA Score), fall in level of inflammatory markers, improvement in respiratory index (pO2/fiO2 ratio), need for mechanical ventilation and need for vasopressors also shown encouraging results but not up to the statistically significant level due to moderate dosage of the drug and small sample size. Conclusion: In the current study, by the observations and results of the double-blind placebo controlled randomised trial, we concluded that as the primary outcome of the study, there was reduction in In-hospital mortality and need for mechanical ventilation in the vitamin C intervention group compared to placebo, although these results did not reach statistical significance due to small sample size and use of moderate dose of IV vitamin C. The secondary outcomes of the study such as improvement in organ failure score (qSOFA Score), fall in level of inflammatory markers, improvement in respiratory index (pO2/fiO2 ratio), need for mechanical ventilation and need for vasopressors also shown encouraging results but not up to the statistically significant level due to moderate dosage of the drug and small sample size. In summary, high dose of intravenous vitamin C may reduce inflammatory reaction, improve oxygen support status, and reduce mortality in COVID-19 patients, without adverse events. High dose intravenous vitamin C may be a promising therapy for patients of moderate to severe COVID-19.

Phytomedicines explored under in vitro and in silico studies against coronavirus: An opportunity to develop traditional medicines.

The widespread COVID-19 pandemic, caused by novel coronavirus SARS-CoV-2, has emanated as one of the most life-threatening transmissible diseases. Currently, the repurposed drugs such as remdesivir, azithromycine, chloroquine, and hydroxychloroquine are being employed in the management of COVID-19 but their adverse effects are a matter of concern. In this regard, alternative treatment options i.e., traditional medicine, medicinal plants, and their phytochemicals, which exhibit significant therapeutic efficacy and show a low toxicity profile, are being explored. The current review aims at unraveling the promising medicinal plants, phytochemicals, and traditional medicines against SARS-CoV-2 to discover phytomedicines for the management of COVID-19 on the basis of their potent antiviral activities against coronaviruses, as demonstrated in various biochemical and computational chemical biology studies. The review consists of integrative and updated information on the potential traditional medicines against COVID-19 and will facilitate researchers to develop traditional medicines for the management of COVID-19.

Hand sanitizer-related calls at the National Poisons Information Centre, India during the lockdown period of the Covid-19 pandemic.

Background Hand sanitizer (HS) has been increasingly used during the Covid-19 pandemic. We compared the telephonic calls received by the National Poisons Information Centre (NPIC), New Delhi, India, related to its unsafe exposure and inappropriate use during the lockdown and prelockdown periods. Methods We analysed and compared telephonic call records of 3 months of pre-lockdown and 3 months of the lockdown and HS-related calls in different age groups and zones during these periods. Results The centre received 4000 calls; of these 1583 (40%) were related to household products of which only 63 (4%) were related to HS. There was an 8-fold increase in the number of calls received at the NPIC during the lockdown compared to the pre-lockdown period seeking medical attention following unsafe exposure or inappropriate use of HS. More calls were received from the south and north zones and, in the majority of these cases, HS was ingested accidentally. In some cases, HS was ingested intentionally for suicide during the lockdown. Conclusions Our study shows that unsafe exposure of HS is common under conditions of stress as seen during the lockdown period of the Covid-19 pandemic. It should be kept out of reach of small children. Further, providing psychological help and counselling to older age groups under conditions of stress are important issues of concern.

Maskne: A side effect of wearing face mask and face mask-wearing attitudes and behavior during 1st, 2nd and 3rd waves of COVID-19 in rural population of Haryana.

Introduction: The term "maskne" originated during the SARS CoV-2 (COVID-19) pandemic; it is a variant of acne associated with continuous wearing of face mask. Maskne is mainly observational, and the most common cause of maskne is contact irritant dermatitis. Materials and methods: The average mask use percentage by OPD cases visiting the hospital for a month in each wave of the COVID -19, that is, in the month of June 2020 during the first wave, in the month of April 2021 during the second wave and in the month of December 2021 during the third wave was calculated. We also included 30 patients with a diagnosis of irritant contact dermatitis aka maskne and 30 patients with diagnosis of acne vulgaris, all >18 years of age from April 2020 to December 2021. Results: 66% of people wore masks coming to hospital in the month of June 2020 (first wave) which increased to 74% during the second wave in the month of April 2021 and during the third wave only 23% of people wore masks in the month of December 2021. Conclusion: Maskne and worsening of acne vulgaris can be due to wearing of dirty face masks for longer duration. Use of moisturizers and regular "mask breaks" are important aspects in management of maskne.

Omicron BA.2 lineage predominance in severe acute respiratory syndrome coronavirus 2 positive cases during the third wave in North India.

Background: Recent studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveal that Omicron variant BA.1 and sub-lineages have revived the concern over resistance to antiviral drugs and vaccine-induced immunity. The present study aims to analyze the clinical profile and genome characterization of the SARS-CoV-2 variant in eastern Uttar Pradesh (UP), North India. Methods: Whole-genome sequencing (WGS) was conducted for 146 SARS-CoV-2 samples obtained from individuals who tested coronavirus disease 2019 (COVID-19) positive between the period of 1 January 2022 and 24 February 2022, from three districts of eastern UP. The details regarding clinical and hospitalized status were captured through telephonic interviews after obtaining verbal informed consent. A maximum-likelihood phylogenetic tree was created for evolutionary analysis using MEGA7. Results: The mean age of study participants was 33.9 ± 13.1 years, with 73.5% accounting for male patients. Of the 98 cases contacted by telephone, 30 (30.6%) had a travel history (domestic/international), 16 (16.3%) reported having been infected with COVID-19 in past, 79 (80.6%) had symptoms, and seven had at least one comorbidity. Most of the sequences belonged to the Omicron variant, with BA.1 (6.2%), BA.1.1 (2.7%), BA.1.1.1 (0.7%), BA.1.1.7 (5.5%), BA.1.17.2 (0.7%), BA.1.18 (0.7%), BA.2 (30.8%), BA.2.10 (50.7%), BA.2.12 (0.7%), and B.1.617.2 (1.3%) lineages. BA.1 and BA.1.1 strains possess signature spike mutations S:A67V, S:T95I, S:R346K, S:S371L, S:G446S, S:G496S, S:T547K, S:N856K, and S:L981F, and BA.2 contains S:V213G, S:T376A, and S:D405N. Notably, ins214EPE (S1- N-Terminal domain) mutation was found in a significant number of Omicron BA.1 and sub-lineages. The overall Omicron BA.2 lineage was observed in 79.5% of women and 83.2% of men. Conclusion: The current study showed a predominance of the Omicron BA.2 variant outcompeting the BA.1 over a period in eastern UP. Most of the cases had a breakthrough infection following the recommended two doses of vaccine with four in five cases being symptomatic. There is a need to further explore the immune evasion properties of the Omicron variant.

In silico evaluation of the inhibitory potential of nucleocapsid inhibitors of SARS-CoV-2: a binding and energetic perspective.

The COVID-19 outbreak brought on by the SARS-CoV-2 virus continued to infect a sizable population worldwide. The SARS-CoV-2 nucleocapsid (N) protein is the most conserved RNA-binding structural protein and is a desirable target because of its involvement in viral transcription and replication. Based on this aspect, this study focused to repurpose antiviral compounds approved or in development for treating COVID-19. The inhibitors chosen are either FDA-approved or are currently being studied in clinical trials against COVID-19. Initially, they were designed to target stress granules and other RNA biology. We have utilized structure-based molecular docking and all-atom molecular dynamics (MD) simulation approach to investigate in detail the binding energy and binding modes of the different anti-N inhibitors to N protein. The result showed that five drugs including Silmitasterib, Ninetanidinb, Ternatin, Luteolin, Fedratinib, PJ34, and Zotatafin were found interacting with RNA binding sites as well as to predicted protein interface with higher binding energy. Overall, drug binding increases the stability of the complex with maximum stability found in the order, Silmitasertib > PJ34 > Zotatatafin. In addition, the frustration changes due to drug binding brings a decrease in local frustration and this decrease is mainly observed in α-helix, ß3, ß5, and ß6 strands and are important for drug binding. Our in-silico data suggest that an effective interaction occurs for some of the tested drugs and prompt their further validation to reduce the rapid outspreading of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Effectiveness of non-invasive respiratory support strategies in patients with COVID-19: A systematic review and meta analysis.

Background: BackgroundThe effectiveness of non-invasive respiratory strategies, namely CPAP and HFNO, in reducing the risk of mortality and tracheal intubation in patients with severe COVID-19 is not well established. Methods: A thorough literature search was conducted across 3 electronic databases (Medline, EMBASE and Cochrane Central) from inception through July 2022. Randomized controlled trials (RCTs) and observational studies assessing the impact of CPAP or HFNO on clinical outcomes in patients infected with COVID-19 were considered for inclusion. End-points included all-cause mortality and risk of tracheal intubation. Evaluations were reported as risk ratios (RRs) with 95% confidence intervals (CI) and analysis was performed using a random effects model. I2 index was used to assess heterogeneity. Results: From the 1041 articles retrieved from initial search, 7 potentially relevant studies (n = 2831 patients) were included in the final analysis. Compared to conventional oxygen therapy, non-invasive respiratory strategies reduced the risk of tracheal intubation (RR = 0.84, [95% CI 0.72, 0.98]; p = 0.02, I2 = 43%) and all-cause mortality (RR = 0.83, [95% CI 0.71-0.97]; p = 0.02, I2 = 0%) in patients infected with COVID-19 However, reduction in length of hospital stay was not significant between the non-invasive respiratory group and conventional oxygen therapy (MD = -0.60, [95% CI -2.17 - 0.98]; p = 0.46, I2 = 26%). Conclusion: This meta-analysis supports the application of non-invasive respiratory strategy is feasible as it can delay the start of tracheal intubation and reduce mortality rates among patients infected with COVID-19.