Is Omicron really mild? – Comparative analysis of comorbidities and disease outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants

Purpose Multiple variants of SARS-CoV-2 from Alpha to Omicron have an estimated 6.1 million deaths globally till date. These variants have been found to vary in transmissibility and severity. The present study deals with comparison of morbidity and mortality with SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants. Materials and method An observational retrospective cohort study was conducted on a cohort of laboratory confirmed patients of SARS-CoV-2 diagnosed by qRT-PCR of nasopharyngeal swabs in periods;April-2021 and January-2022;that were sequenced and variants were recorded. Patients were invited for a telephonic interview after voluntary and informed consent was obtained from each participant wherein, the demographics, co-morbidities, oxygen requirement and mortality outcomes of the patients were enquired about. Results A total of 200 patients, with 100 from each period were included in the study. Major comorbidities in patients included hypertension, diabetes mellitus and pulmonary disease. Patients who succumbed to the Delta variant (26%) were higher as compared to the Omicron variant (10%);with the elderly (68 ​± ​9.7 ​years) having significant mortality during the Omicron variant. The mortality was increased in patients with comorbidities as with hypertension (53.8%, 70%), diabetes mellitus (26.9%, 40%), chronic pulmonary disease (30.8%, 20%), and smoking (15.4%, 40%) in the patients infected with both Delta and Omicron variants, respectively. Conclusion The study concluded that the newer strains of SARS-CoV-2 have potential of high transmissibility and milder disease for the population by large, however, for patients with comorbidities have a higher proportion of adverse outcomes, irrespective of the variant.

Molecular Docking and Simulation Analysis of Cyclopeptides as Anticancer Agents

Background: Cancer is a leading cause of death for people worldwide, in addition to the rise in mortality rates attributed to the Covid epidemic. This allows scientists to do additional research. Here, we have selected Integerrimide A, cordy heptapeptide, and Oligotetrapeptide as the three cyclic proteins that will be further studied and investigated in this context.Methods: Docking research was carried out using the protein complexes 1FKB and 1YET, downloaded from the PDB database and used in the docking investigations. Cyclopeptides have been reported to bind molecularly to human HSP90 (Heat shock protein) and FK506. It was possible to locate HSP90 in Protein Data Banks 1YET and 1FKB. HSP90 was retrieved from Protein Data Bank 1YET and 1FKB. Based on these findings, it is possible that the anticancer effects of Int A, Cordy, and Oligo substances could be due to their ability to inhibit the mTOR rapamycin binding domain and the HSP90 Geldanamycin binding domain via the mTOR and mTOR chaperone pathways. During the calculation, there were three stages: system development, energy reduction, and molecular dynamics (also known as molecular dynamics). Each of the three compounds demonstrated a binding affinity for mTOR's Rapamycin binding site that ranged from -6.80 to -9.20 Kcal/mol (FKB12).Results: An inhibition constant Ki of 181.05 nM characterized Cordy A with the highest binding affinity (-9.20 Kcal/mol). Among the three tested compounds, Cordy A was selected for MD simulation. HCT116 and B16F10 cell lines were used to test each compound's anticancer efficacy. Doxorubicin was used as a standard drug. The cytotoxic activity of substances Int A, Cordy A, and Oligo on HCT116 cell lines was found to be 77.65 μM, 145.36 μM, and 175.54 μM when compared to Doxorubicin 48.63 μM, similarly utilizing B16F10 cell lines was found to be 68.63 μM, 127.63 μM, and 139.11 μM to Doxorubicin 45.25 μM.Conclusion: Compound Cordy A was more effective than any other cyclic peptides tested in this investigation.

Performance analysis and environmental feasibility of bifacial photovoltaic thermal dryer with heat storage

In Covid19, it was observed that dehydrated commodity (fruits, vegetables, meat, etc.) was the most sustainable because of their long life and availability. The stored product market grew very fast after Covid19. It was predicted that the dehydrated circular economy would be the future of food demand and supply. The greenhouse dryer (GD) was the most economical and environmentally viable among various drying techniques. However, the problem associated with GD was low operating hours, sustainability, heat loss from the North wall, and operation after sunset. The present study incorporated a bifacial photovoltaic thermal (BIFPVT) on the roof, Lauric acid as a phase change material (PCM), and an aluminium foil-wrapped thermocol (Polystyrene foam) on the north wall of the GD as an insulation to overcome the above-said problem. The thermal efficiency of the modified greenhouse dryer was found to be lie in the range of 26–54%. In contrast, the electrical efficiency was found to be 20.1%. The integration of the thermal energy storage (TES) system runs the system even after sunset and improves the operation hours. The designed system not only makes the system self-sustainable but also mitigates 3136 kg of CO2 in its whole life span. The modified TES can further improve the thermal performance of the GD. A PCM-integrated BIFPVT greenhouse dryer is recommended for cleaner production.

Surveillance of omicron variant in Kangra District of Himachal Pradesh, India during the 3rd disease wave of COVID-19.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) wave has fluctuated erratically around the globe over the past three years of the pandemic, sometimes declining and at other times surging. The cases of infection in India have remained low, despite the continued surge of Omicron sub-lineages reported in a few countries. In this study, we determined the presence of the circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains in the population of Kangra District, Himachal Pradesh, India. METHODOLOGY: In vitro diagnostic real-time reverse transcriptase polymerase chain reaction (RT-qPCR) was performed using Tata MD CHECK RT-PCR Omisure kit (Tata Medical and Diagnostics Limited, Maharashtra, India), to detect the presence of Omicron in target samples. A total of 400 samples were analyzed in this study; 200 each for the second and third waves, respectively. The S gene target failure (SG-TF) and S gene mutation amplification (SG-MA) primer-probe sets were used. RESULTS: Our results corroborated that during the third wave, SG-MA amplification was noted, while amplification of SG-TF was not, and vice versa in the case of the second wave, indicating that all the tested patients were infected with the Omicron variant during the third wave, while Omicron was absent during the second wave. CONCLUSIONS: This study added more information about the prevalence of Omicron variants during the third wave in the chosen area, and it projected a use of in vitro RT-qPCR method for rapid prospective determination of the prevalence of the variant of concern (VOC) in developing countries with limited sequencing facility.

Gold, crude oil, bitcoin and Indian stock market: recent confirmation from nonlinear ARDL analysis

PurposeThis paper investigates the causality among gold prices, crude oil prices, bitcoin and stock prices by using daily data from January 2014 to December 2021. The study also examines the data during the COVID-19 outbreak from January 2020 to December 2021.Design/methodology/approachTo estimate the long- and short-run causality, this study considers the nonlinear autoregressive distributed lag (NARDL) cointegration test.FindingsThe analysis found the existence of an asymmetric long-run cointegration among selected assets. Findings indicate that positive changes in bitcoin do not affect stock market in the long term. Changes in crude oil prices have a significant impact on stock prices. Moreover, it is observed that variations in the stock prices trigger a negative impact on gold prices. During the COVID-19 period, the study notices the presence of an asymmetric long-term cointegration between selected assets except bitcoin. Besides, findings revealed that negative price adjustments in gold lead to significant positive shocks in stock market.Originality/valueThese results provide critical information for policy performers and researchers to develop new strategies. Policy regulators can also consider the potential effects of the COVID-19 outbreak while developing strategies for investment decisions.

Ocular manifestations of COVID-19 in pediatric patients.

The coronavirus disease-19 (COVID-19) infection may remain asymptomatic or may have several different presentations. Although this disease primarily affects the respiratory system, systemic manifestations affecting the gastrointestinal, cardiovascular, neurological, otorhinolaryngologic, and ophthalmic systems have been reported. Ophthalmic signs may be the first and only sign of COVID-19 infection in children. In the current narrative review, we report the ophthalmic manifestations of COVID-19 in the pediatric age cohort. We performed a comprehensive literature search for the publications on ophthalmic manifestations of COVID-19 in children between 1 March 2020 and 1 January 2022 and compiled the ophthalmic manifestations of this entity among the pediatric population. Conjunctivitis is the most common ophthalmic manifestation in children and can develop at any stage of the disease. Ophthalmic manifestations are seen more commonly in children with severe systemic disease. Long-term and indirect consequence of the COVID-19 disease is the rise of myopia among children. Ophthalmic signs may be the first and only sign of COVID-19 infection in children. Pediatricians, as well as ophthalmologists, must keep observing all children with COVID-19 closely for ophthalmic signs.

Potent and selective covalent inhibition of the papain-like protease from SARS-CoV-2.

Direct-acting antivirals are needed to combat coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The papain-like protease (PLpro) domain of Nsp3 from SARS-CoV-2 is essential for viral replication. In addition, PLpro dysregulates the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 protein from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics. Here we design a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophile onto analogs of the noncovalent PLpro inhibitor GRL0617. The most potent compound inhibits PLpro with kinact/KI = 9,600 M-1 s-1, achieves sub-µM EC50 values against three SARS-CoV-2 variants in mammalian cell lines, and does not inhibit a panel of human deubiquitinases (DUBs) at >30 µM concentrations of inhibitor. An X-ray co-crystal structure of the compound bound to PLpro validates our design strategy and establishes the molecular basis for covalent inhibition and selectivity against structurally similar human DUBs. These findings present an opportunity for further development of covalent PLpro inhibitors.

Optical Coherence Tomography Angiography Parameters of the Retina in SARS-CoV-2 Recovered Subjects.

INTRODUCTION: This study aims to evaluate retinochoroidal optical coherence tomography angiography (OCTA) parameters in patients recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This study was an observational study that included 80 subjects being discharged after having negative reports on the reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 to evaluate OCTA parameters of the retina. The subjects underwent an ophthalmic evaluation that included best-corrected visual acuity (BCVA), intraocular pressure (IOP), color vision (CV), contrast sensitivity (CS), and optical coherence tomography (OCT) parameters. OCTA was done for all patients and was evaluated for foveal avascular zone (FAZ) area, perimeter, and circularity index, and vessel density (VD) in superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR), outer retina chorio-capillaries (ORCC), chorio-capillaries (CC), and choroid (C) using 3 x 3 mm scans. The OCTA parameters were compared with normative data of the Indian population for various parameters in question. RESULTS: The subjects included 54/80 (67.5%) males and 26/80 (32.5%) females having a mean age of 52.40 ± 15.71 (18-60) years. The systemic evaluation revealed 38.75% of subjects had hypertension, 30% had diabetes, 20% had kidney disease, 5% had tuberculosis, and 3.75% had coronary artery disease. The mean distance BCVA was logarithm of the minimum angle of resolution (LogMAR) (1.17 ± 0.22), mean IOP was 17.0 ± 4.0 mmHg, mean CS was 2.13 ± 0.36, 50.62% of subjects had normal CV on Farnsworth test while 47% had tritanopia, and none of the subjects had red-green CV defect on Ishihara plates. The OCT scan was normal in 90% of eyes while the posterior vitreous detachment was seen in 4% of eyes, broad vitreomacular adhesion in 2.5% of eyes, and the globally adherent epiretinal membrane was seen in 2.5% of eyes. The mean central macular thickness (CMT) measured 245.14 ± 28.41 micrometers. The mean FAZ area measured 0.37 ± 0.15 mm2, the perimeter was 3.28 ± 1.08 mm, and the circularity index measured 0.41 ± 0.10. The average VD in SCP measured 16.06 ± 12.29, in DCP measured 9.11 ± 8.75, in OR measured 6.38 ± 7.37, in ORCC measured 42.53 ± 12.46, in CC measured 25.83 ± 16.31, and in C measured 25.52 ± 17.49. The VD in coronavirus disease 2019 (COVID-19) subjects was significantly lesser than that in the healthy Indian population in all layers except ORCC. CONCLUSIONS: The SARS-CoV-2 recovered subjects have a reduced VD in retinochoroidal layers from COVID-19, an underlying systemic disease, or both. The CS values fall within normal limits. Several subjects show tritanopia on the Farnsworth test but no red-green CV defect on Ishihara plates.

Mammalian hybrid prophagophore is a precursor to autophagosomes.

The precursors to mammalian autophagosomes originate from preexisting membranes contributed by a number of sources, and subsequently enlarge through intermembrane lipid transfer, then close to sequester the cargo, and merge with lysosomes to degrade the cargo. Using cellular and in vitro membrane fusion analyses coupled with proteomic and biochemical studies we show that autophagosomes are formed from a hybrid membrane compartment referred to as a prophagophore or HyPAS (hybrid preautophagosomal structure). HyPAS is initially LC3-negative and subsequently becomes an LC3-positive phagophore. The prophagophore emerges through fusion of RB1CC1/FIP200-containing vesicles, derived from the cis-Golgi, with endosomally derived ATG16L1 membranes. A specialized Ca2+-responsive apparatus controls prophagophore biogenesis and can be modulated by pharmacological agents such as SIGMAR1 agonists and antagonists including chloroquine. Autophagic prophagophore formation is inhibited during SARS-CoV-2 infection and is recapitulated by expression of SARS-CoV-2 nsp6. These findings show that mammalian autophagosomal prophagophores emerge via the convergence of secretory and endosomal pathways in a process that is targeted by microbial factors including coronaviral membrane proteins.Abbreviations: CLEM, correlative light and electron microscopy; CQ, chloroquine; HyPAS, hybrid preautophagosomal; strcuture/prophagophore; LC3, microtubule associated protein 1 light chain 3; RUPEX, a combination of RUSH and APEX2 systems; SARS-CoV-2, SARS-CoV-2 virus, causative agent of COVID19.

The Predictive Score for Patients Hospitalized With COVID-19 in Resource-Limited Settings.

Background and aims The second wave of coronavirus disease 2019 (COVID-19) has been devastating in India and many developing countries. The mortality reported has been 40% higher than in the first wave, overwhelming the nation's health infrastructure. Despite a better understanding of the disease and established treatment protocols including steroids and heparin, the second wave was disastrous. Subsequent waves have the potential to further cripple healthcare deliveries, also affecting non-COVID-19 care across many developing economies. It is then important to identify and triage high-risk patients to best use the limited resources. Routine tests such as neutrophil and monocyte counts have been identified but have not been successfully validated uniformly, and their utility is still being understood in COVID-19. Various predictive models that are available require online resources and calculators and additionally await validation across all populations. These, although useful, might not be available or accessible across all institutions. It is then important to identify easy-to-use scores that utilize tests done routinely. In identifying with this goal, we did a retrospective review of the institutional database to identify potential predictors of intensive care unit (ICU) admission and mortality in patients hospitalized during the second wave who accessed healthcare at our academic setup. Results Three predictors of mortality and four predictors of ICU admission were identified. Absolute neutrophil count was a common predictor of both ICU admission and mortality but with two separate cut points. An absolute neutrophil count of >4,200 predicted need for ICU admission (odds ratio (OR): 3.1 (95% confidence interval (CI): 2.0, 4.8)), and >7,200 predicted mortality (adjusted OR: 4.2 (95% CI: 1.9, 9.4)). We observed that a blood urea level greater than 45 was predictive of needing ICU care (adjusted OR: 8.0 (95% CI: 3.7, 17.6)). In our dataset, serum ferritin of >500 was predictive of ICU admission (adjusted OR: 2.7 (95% CI: 1.2, 5.9)). We noted a right shift of partial pressure (p50 is the oxygen tension at which hemoglobin is 50% saturated) (p50c) in SARS-CoV-2 as a predictor of ICU care (OR: 2.6 (95% CI: 1.7, 3.9)) when partial pressure is >26.5. In our analysis, a serum protein of less than 7 g/dL (OR: 2.8 (95% CI: 1.7, 4.4)) was a predictive variable for ICU admission. An LDH value of >675 was predictive of severity with a need for ICU admission (OR: 9.2 (95% CI: 5.4, 15.5)) in our series. We then assigned a score to each of the predictive variables based on the adjusted odds ratio. Conclusion We identified a set of easy-to-use predictive variables and scores to recognize the subset of patients hospitalized with COVID-19 with the highest risk of death or clinical worsening requiring ICU care.

COVID-19 Vaccine-Associated Ocular Adverse Effects: An Overview.

BACKGROUND: To address the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination efforts were initiated across the globe in December 2020 and are continuing. We report the onset interval and clinical presentations of ocular adverse effects following SARS-CoV-2 vaccination. METHODS: For this narrative review, articles in the English language, published between 1 January 2020 to 1 September 2022, were included to formulate a list of the reported ocular adverse effects of different COVID-19 vaccines. RESULTS: During this period, ocular adverse effects have been reported with BNT162b2 (Pfizer), mRNA-1273 (Moderna), AZD-1222 (AstraZeneca), and Ad26.COV2.S (Johnson & Johnson) vaccines. Endothelial graft rejection, herpes simplex virus keratitis, herpes zoster ophthalmicus, anterior uveitis, eyelid edema, purpuric rashes, ischemic optic neuropathy, and cranial nerve palsies were the most reported with BNT163b2. Retinal hemorrhages, vascular occlusions, and angle closure glaucoma were the most reported with AZD-1222. Most of the ocular adverse effects reported in the literature had a good to fair prognosis with appropriate management. CONCLUSIONS: Evidence regarding the ocular adverse effects does not outweigh the benefits of SARS-CoV-2 vaccination in patients with pre-existing systemic or ophthalmic diseases. This review provides insights into the possible temporal association between reported ocular adverse events and SARS-CoV-2 vaccines; however, further investigations are required to identify the link between potential causality and pathological mechanisms.

Comparison of safety and efficacy of convalescent plasma with fresh frozen plasma in severe covid-19 patients.

BACKGROUND: Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. METHODS: One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. RESULTS: The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.

Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial).

IMPORTANCE: No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation. OBJECTIVE: To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients. DESIGN, SETTING AND PARTICIPANTS: A multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group. INTERVENTION: One group received COPLA with SMT (n=200), and another group received SMT only (n=200). MAIN OUTCOME MEASURES: Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events. RESULTS: The median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7-13) (p=0.328). The median duration of O2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO2/FiO2 ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80-80)) were higher than SMT group (0 (IQR 0-80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group. CONCLUSION AND RELEVANCE: Convalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes. TRIAL REGISTRATION NUMBER: NCT04425915.

Inactivated whole-virion vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern.

BBV152 is a whole-virion inactivated vaccine based on the Asp614Gly variant. BBV152 is the first alum-imidazoquinolin-adjuvanted vaccine authorized for use in large populations. Here we characterized the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months post vaccination. We report that the magnitude of vaccine-induced spike and nucleoprotein antibodies was comparable with that produced after infection. Receptor binding domain-specific antibodies declined against variants in the order of Alpha (B.1.1.7; 3-fold), Delta (B.1.617.2; 7-fold) and Beta (B.1.351; 10-fold). However, pseudovirus neutralizing antibodies declined up to 2-fold against the Delta followed by the Beta variant (1.7-fold). Vaccine-induced memory B cells were also affected by the Delta and Beta variants. The SARS-CoV-2-specific multicytokine-expressing CD4+ T cells were found in ~85% of vaccinated individuals. Only a ~1.3-fold reduction in efficacy was observed in CD4+ T cells against the Beta variant. We found that antigen-specific CD4+ T cells were present in the central memory compartment and persisted for at least up to 6 months post vaccination. Vaccine-induced CD8+ T cells were detected in ~50% of individuals. Importantly, the vaccine was capable of inducing follicular T helper cells that exhibited B-cell help potential. These findings show that inactivated vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern that persists for at least 6 months after vaccination.

Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) of SARS-CoV-2 spike infectivity and pathogenicity: A comparative sequence and structural-based computational assessment.

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.

Ocular sequelae in severe COVID-19 recovered patients of second wave.

Purpose: To evaluate the retinal microvascular changes in patients, recovered from severe COVID-19 during the second wave of the pandemic in North India. Methods: In this observational cross-sectional study, 70 eyes of 35 patients who recovered from severe COVID-19 during the second wave underwent detailed ophthalmic evaluation 4-6 weeks after discharge. Twelve controls were also enrolled, and the difference in the findings between the case and control groups on optical coherence tomography (OCTA) were studied. Result: The ages of study participants ranged from 27 to 60 years with the male:female ratio being 1.05:1. The fundus changes suggestive of ischemia in the form of cotton wool spots and vascular tortuosity were seen in 25 eyes (35.71%). Increased venous tortuosity was the most common finding seen in 23 eyes (32.85%), of which 10 eyes (28.57%) had concurrent hypertensive retinopathy (HTR) changes. There was a significant reduction in the mean vascular density (VD) and perfusion density (PD) for both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at inner, outer ring, and whole (P < 0.05). Foveal avascular zone was significantly enlarged in both the SCP (P = 0.01) and the DCP (P = 0.03). The mean ganglion cell-inner plexiform layer (GC-IPL) was significantly reduced in comparison to controls (P < 0.001). Conclusion: Severe COVID-19 can result in microvascular changes at the macula in the form of reduction in vascular and perfusion density, which can be evaluated using OCTA. As structural changes precede functional changes, a close watch is recommended in patients showing compromise in retinal microvasculature.

Mucormycosis in the Setting of the Covid-19 Pandemic in Patients without Exposure to Steroids and Oxygen: A Case Series from a Tertiary Care Center in North India

Background: Sudden surge of mucormycosis cases in India needs an urgent attention as multiple factors have been implicated. However, diabetes mellitus remains to be one of the most important and modifiable factors. Methodology: We prospectively followed 11 patients with mucormycosis in May 2021 and June 2021, admitted to our hospital to study the possible etiologies. Results: Out of the 11 patients, six were males and five were females, with an average age of 52.45 years. Type 2 diabetes mellitus was the ubiquitous comorbidity, and every patient presented with uncontrolled hyperglycemia (six out of them were in diabetic ketoacidosis). Glycated hemoglobin levels ranged from 10.2% to 15.1%. Out of 11 patients, four patients were non-COVID, whereas five patients had a history of COVID-19 infection. All these five post COVID-19 patients presented approximately 20 days after recovery, out of which one patient had severe infection who was hospitalized. The remaining two patients were COVID-19-positive. Out of 11 patients, 10 patients had rhino-orbital mucormycosis at presentation, among which four patients had cerebral involvement, and one out of them later developed invasive disease. However, one patient had only pulmonary mucormycosis at presentation. Serum ferritin was raised in all the patients, and six had serum zinc levels below the reference range. Serum flow cytometry showed leukopenia with normal CD4:CD8 ratio in seven patients. In the clinical outcome, six patients expired, whereas five patients responded to the treatment and were discharged on oral posaconazole therapy. Conclusion: From our study, it is quite evident that uncontrolled diabetes and its complications such as diabetic ketoacidosis were an important risk factor for the occurrence of mucormycosis in COVID-19 patients as well as non-COVID-19 patients, even without exposure to steroids or oxygen. Thus, blood glucose levels should be kept at optimum level during the management of COVID-19 patients. [ FROM AUTHOR] Copyright of Indian Journal of Medical Specialities is the property of Wolters Kluwer India Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Omicron and Delta variant of SARS-CoV-2: A comparative computational study of spike protein.

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.

Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Global randomised controlled trials of the anti-IL-6 receptor antibody tocilizumab in patients admitted to hospital with COVID-19 have shown conflicting results but potential decreases in time to discharge and burden on intensive care. Tocilizumab reduced progression to mechanical ventilation and death in a trial population enriched for racial and ethnic minorities. We aimed to investigate whether tocilizumab treatment could prevent COVID-19 progression in the first multicentre randomised controlled trial of tocilizumab done entirely in a lower-middle-income country. METHODS: COVINTOC is an open-label, multicentre, randomised, controlled, phase 3 trial done at 12 public and private hospitals across India. Adults (aged ≥18 years) admitted to hospital with moderate to severe COVID-19 (Indian Ministry of Health grading) confirmed by positive SARS-CoV-2 PCR result were randomly assigned (1:1 block randomisation) to receive tocilizumab 6 mg/kg plus standard care (the tocilizumab group) or standard care alone (the standard care group). The primary endpoint was progression of COVID-19 (from moderate to severe or from severe to death) up to day 14 in the modified intention-to-treat population of all participants who had at least one post-baseline assessment for the primary endpoint. Safety was assessed in all randomly assigned patients. The trial is completed and registered with the Clinical Trials Registry India (CTRI/2020/05/025369). FINDINGS: 180 patients were recruited between May 30, 2020, and Aug 31, 2020, and randomly assigned to the tocilizumab group (n=90) or the standard care group (n=90). One patient randomly assigned to the standard care group inadvertently received tocilizumab at baseline and was included in the tocilizumab group for all analyses. One patient randomly assigned to the standard care group withdrew consent after the baseline visit and did not receive any study medication and was not included in the modified intention-to-treat population but was still included in safety analyses. 75 (82%) of 91 in the tocilizumab group and 68 (76%) of 89 in the standard care group completed 28 days of follow-up. Progression of COVID-19 up to day 14 occurred in eight (9%) of 91 patients in the tocilizumab group and 11 (13%) of 88 in the standard care group (difference -3·71 [95% CI -18·23 to 11·19]; p=0·42). 33 (36%) of 91 patients in the tocilizumab group and 22 (25%) of 89 patients in the standard care group had adverse events; 18 (20%) and 15 (17%) had serious adverse events. The most common adverse event was acute respiratory distress syndrome, reported in seven (8%) patients in each group. Grade 3 adverse events were reported in two (2%) patients in the tocilizumab group and five (6%) patients in the standard care group. There were no grade 4 adverse events. Serious adverse events were reported in 18 (20%) patients in the tocilizumab group and 15 (17%) in the standard care group; 13 (14%) and 15 (17%) patients died during the study. INTERPRETATION: Routine use of tocilizumab in patients admitted to hospital with moderate to severe COVID-19 is not supported. However, post-hoc evidence from this study suggests tocilizumab might still be effective in patients with severe COVID-19 and so should be investigated further in future studies. FUNDING: Medanta Institute of Education and Research, Roche India, Cipla India, and Action COVID-19 India.