Post-COVID Syndrome and Severity of COVID-19: A Cross-Sectional Epidemiological Evaluation From North India.

Background COVID-19 has now lasted for more than two years as a pandemic and has had enduring effects on the health of people as the post-COVID syndrome. Recent literature has shown the long-term effects of COVID-19 on various organ systems, including but not limited to respiratory, cardiovascular, neurological, musculoskeletal, and gastrointestinal systems. Methods and objectives We aimed to estimate the prevalence of post-acute COVID symptoms in a tertiary care center in northern India; observe the effects of the demographic profile of age, BMI, gender, and presence of comorbidities on the persistence of post-COVID syndrome, and explore any correlation between the severity of COVID-19 disease and the persistence of post-COVID symptoms. We designed a survey containing structured questions evaluating post-COVID symptoms beyond three weeks (post-acute COVID phase), six weeks (post-COVID phase), and 12 weeks of acute illness. It was administered online.  Results Prevalence of post-COVID symptoms both after three and six weeks was reported to be 16.67% and 7.37%, respectively. The most common symptoms to persist were musculoskeletal symptoms (fatigue), followed by upper respiratory symptoms. Disease severity (p<0.05), BMI (p<0.05), and comorbidities were seen to affect post-COVID symptoms significantly, whereas gender and age of the patient had no significant effect. Disease severity significantly affected the persistence of post-COVID symptoms up to 12 weeks; however, this effect does not hold true in long COVID haulers. Also, the risk of developing persistent post-acute COVID symptoms was more in moderate to severe disease than in mild disease. Conclusion The pandemic might be close to over, but it is not out of our lives yet, and the persistence of post-COVID symptoms is exigent.

An Unusual Diagnosis of Sporadic Type III Osteogenesis Imperfecta in the First Day of Life.

Osteogenesis imperfecta (OI) is a group of rare, permanent genetic bone disorders resulting from the mutations in genes encoding type 1 collagen. It usually is inherited by an autosomal dominant pattern, but it can sometimes occur sporadically. Among the four main types, type III is the most severe type which presents with multiple bone fractures, skeletal deformities, blue sclera, hearing, and dental abnormalities. It is estimated that only 1 in 20,000 cases of OI are detected during infancy, and the diagnosis carries a poor prognosis. This case is reported for the rarity of sporadic OI diagnosis in neonates. We present a case of a 1-day-old neonate following a normal vaginal delivery referred to our center in the view of low birth weight and multiple bony deformities. Physical examination revealed an ill-looking child with poor suckling, gross bony deformities in upper and lower limbs, and blue sclera. X-ray showed thin gracile bones with multiple bone fractures. Echocardiography revealed a 4 mm patent ductus arteriosus. The patient was diagnosed with type III OI with patent ductus arteriosus. Though OI is rare in neonates and infants, it should be considered in the differentials in a newborn presenting with multiple bony deformities regardless of family history, history of trauma, or physical abuse. OI is also associated with cardiac anomalies such as the atrial septal defect and patent ductus arteriosus for which echocardiography is recommended routinely.

Disparities in Telehealth Utilization in a Population of Publicly Insured Children During the COVID-19 Pandemic.

Telehealth became a crucial vehicle for health care delivery in the United States during the COVID-19 pandemic. However, little research exists on inequities in telehealth utilization among the pediatric population. This study examines disparities in telehealth utilization in a population of publicly insured children. This observational, retrospective study used administrative data from Alabama's stand-alone Children's Health Insurance Program, ALL Kids. Rates of any telehealth use for March to December 2020 were examined. In addition-to capture lack of health care utilization-rates of having no medical claims were examined and compared with March to December 2019 and 2018. Multinomial logit models were estimated to investigate how telehealth use and having no medical claims (reference category: having medical claims but no telehealth) were associated with race/ethnicity, rural-urban residence, and family income. Of the 106,478 enrollees over March to December 2020, 13.4% had any telehealth use and 24.7% had no medical claims. The latter was greater than no medical claims in 2019 (19.5%) and 2018 (20.7%). Black and Hispanic children had lower odds of any telehealth use (odds ratio [OR]: 0.81, P < 0.01; OR: 0.68, P < 0.01) and higher odds of no medical claims (OR: 1.11, P < 0.05; OR: 1.73, P < 0.05) than non-Hispanic White children. Rural residents had lower odds of telehealth use than urban residents. Those in the highest family income-based fee group had higher odds of telehealth use than the lowest family income-based fee group. As telehealth will likely continue to play an important role in health care delivery, additional efforts/investments are required to ensure telehealth does not further exacerbate inequities in pediatric health care access.

Antidrug resistance in the Indian ambient waters of Ahmedabad during the COVID-19 pandemic.

The ongoing COVID-19 pandemic increases the consumption of antimicrobial substances (ABS) due to the unavailability of approved vaccine(s). To assess the effect of imprudent consumption of ABS during the COVID-19 pandemic, we compare the 2020 prevalence of antidrug resistance (ADR) of Escherichia coli (E. coli) with a similar survey carried out in 2018 in Ahmedabad, India using SARS-CoV-2 gene detection as a marker of ABS usage. We found a significant ADR increase in 2020 compared to 2018 in ambient water bodies, harbouring a higher incidence of ADR E.coli towards non-fluoroquinolone drugs. Effective SARS-CoV-2 genome copies were found to be associated with the ADR prevalence. The prevalence of ADR depends on the efficiency of WWTPs (Wastewater Treatment Plants) and the catchment area in its vicinity. In the year 2018 study, prevalence of ADR was discretely distributed, and the maximum ADR prevalence recorded was ~60%; against the current homogenous ADR increase, and up to 85% of maximum ADR among the incubated E.coli isolated from the river (Sabarmati) and lake (Chandola and Kankaria) samples. Furthermore, wastewater treatment plants showed less increase in comparison to the ambient waters, which eventually imply that although SARS-CoV-2 genes and faecal pollution may be diluted in the ambient waters, as indicated by low Ct-value and E.coli count, the danger of related aftermath like ADR increase cannot be nullified. Also, Non-fluoroquinolone drugs exhibited overall more resistance than quinolone drugs. Overall, this is probably the first-ever study that traces the COVID-19 pandemic imprints on the prevalence of antidrug resistance (ADR) through wastewater surveillance and hints at monitoring escalation of other environmental health parameters. This study will make the public and policyholders concerned about the optimum use of antibiotics during any kind of treatment.

Transport Circuit during COVID-19 Crisis: A Simple Modification of the Bain's Circuit for Safety of Healthcare Workers.

How to cite this article: Burman S, Sharma PB, Tyagi M, Singh GP, Chaturvedi A. Transport Circuit during COVID-19 Crisis: A Simple Modification of the Bain's Circuit for Safety of Healthcare Workers. Indian J Crit Care Med 2020;24(12):1281-1283.

Structure-Based Virtual Screening and Biochemical Validation to Discover a Potential Inhibitor of the SARS-CoV-2 Main Protease.

The recent pandemic caused by SARS-CoV-2 has led the world to a standstill, causing a medical and economic crisis worldwide. This crisis has triggered an urgent need to discover a possible treatment strategy against this novel virus using already-approved drugs. The main protease (Mpro) of this virus plays a critical role in cleaving the translated polypeptides that makes it a potential drug target against COVID-19. Taking advantage of the recently discovered three-dimensional structure of Mpro, we screened approved drugs from the Drug Bank to find a possible inhibitor against Mpro using computational methods and further validating them with biochemical studies. The docking and molecular dynamics study revealed that DB04983 (denufosol) showed the best glide docking score, -11.884 kcal/mol, and MM-PBSA binding free energy, -10.96 kcal/mol. Cobicistat, cangrelor (previous computational studies in our lab), and denufosol (current study) were tested for the in vitro inhibitory effects on Mpro. The IC50 values of these drugs were ∼6.7 µM, 0.9 mM, and 1.3 mM, respectively, while the values of dissociation constants calculated using surface plasmon resonance were ∼2.1 µM, 0.7 mM, and 1.4 mM, respectively. We found that cobicistat is the most efficient inhibitor of Mpro both in silico and in vitro. In conclusion, cobicistat, which is already an FDA-approved drug being used against HIV, may serve as a good inhibitor against the main protease of SARS-CoV-2 that, in turn, can help in combating COVID-19, and these results can also form the basis for the rational structure-based drug design against COVID-19.

Screening and evaluation of approved drugs as inhibitors of main protease of SARS-CoV-2.

The COVID-19 pandemic caused by SARS-CoV-2 has emerged as a global catastrophe. The virus requires main protease for processing the viral polyproteins PP1A and PP1AB translated from the viral RNA. In search of a quick, safe and successful therapeutic agent; we screened various clinically approved drugs for the in-vitro inhibitory effect on 3CLPro which may be able to halt virus replication. The methods used includes protease activity assay, fluorescence quenching, surface plasmon resonance (SPR), Thermofluor® Assay, Size exclusion chromatography and in-silico docking studies. We found that Teicoplanin as most effective drug with IC50 ~ 1.5 µM. Additionally, through fluorescence quenching Stern-Volmer quenching constant (KSV) for Teicoplanin was estimated as 2.5 × 105 L·mol-1, which suggests a relatively high affinity between Teicoplanin and 3CLPro protease. The SPR shows good interaction between Teicoplanin and 3CLPro with KD ~ 1.6 µM. Our results provide critical insights into the mechanism of action of Teicoplanin as a potential therapeutic against COVID-19. We found that Teicoplanin is about 10-20 fold more potent in inhibiting protease activity than other drugs in use, such as lopinavir, hydroxychloroquine, chloroquine, azithromycin, atazanavir etc. Therefore, Teicoplanin emerged as the best inhibitor among all drug molecules we screened against 3CLPro of SARS-CoV-2.

Identification of promising drug candidates against NSP16 of SARS-CoV-2 through computational drug repurposing study.

The recent outbreak of the SARS-CoV-2 virus leading to the disease COVID 19, a global pandemic has resulted in an unprecedented loss of life and economy worldwide. Hence, there is an urgent need to discover effective drugs to control this pandemic. NSP16 is a methyltransferase that methylates the ribose 2'-O position of the viral nucleotide. Taking advantage of the recently solved structure of NSP16 with its inhibitor, S-Adenosylmethionine, we have virtually screened FDA approved drugs, drug candidates and natural compounds. The compounds with the best docking scores were subjected to molecular dynamics simulations followed by binding free energy calculations using the MM-PBSA method. The known drugs which were identified as potential inhibitors of NSP16 from SARS-CoV-2 included DB02498, DB03909, DB03186, Galuteolin, ZINC000029416466, ZINC000026985532, and ZINC000085537017. DB02498 (Carba-nicotinamide-adenine-dinucleotide) is an approved drug which has been used since the late 1960s in intravenous form to significantly lessen withdrawal symptoms from a variety of drugs and alcohol addicts and it has the best MM-PBSA binding free energy of-12.83 ± 0.52 kcal/mol. The second best inhibitor, Galuteolin is a natural compound that inhibits tyrosinase enzyme with MM-PBSA binding free energy value of -11.21 ± 0.47 kcal/mol. Detailed ligand and protein interactions were analyzed and common residues across SARS-CoV, SARS-CoV-2, and MERS-CoV were identified. We propose Carba-nicotinamide-adenine-dinucleotide and Galuteolin as the potential inhibitors of NSP16. The results in this study can be used for the treatment of COVID-19 and can also form the basis of rational drug design against NSP16 of SARS-CoV-2.

Identification of potential drug candidates to combat COVID-19: a structural study using the main protease (mpro) of SARS-CoV-2.

The recent outbreak of the SARS-CoV-2 virus leading to the disease COVID 19 has become a global pandemic that is spreading rapidly and has caused a global health emergency. Hence, there is an urgent need of the hour to discover effective drugs to control the pandemic caused by this virus. Under such conditions, it would be imperative to repurpose already known drugs which could be a quick and effective alternative to discovering new drugs. The main protease (Mpro) of SARS-COV-2 is an attractive drug target because of its essential role in the processing of the majority of the non-structural proteins which are translated from viral RNA. Herein, we report the high-throughput virtual screening and molecular docking studies to search for the best potential inhibitors against Mpro from FDA approved drugs available in the ZINC database as well as the natural compounds from the Specs database. Our studies have identified six potential inhibitors of Mpro enzyme, out of which four are commercially available FDA approved drugs (Cobicistat, Iopromide, Cangrelor, and Fortovase) and two are from Specs database of natural compounds (Hopeaphenol and Cyclosieversiodide-A). While Cobicistat and Fortovase are known as HIV drugs, Iopromide is a contrast agent and Cangrelor is an anti-platelet drug. Furthermore, molecular dynamic (MD) simulations using GROMACS were performed to calculate the stability of the top-ranked compounds in the active site of Mpro. After extensive computational studies, we propose that Cobicistat and Hopeaphenol show potential to be excellent drugs that can form the basis of treating COVID-19 disease.Communicated by Ramaswamy H. Sarma.

Pediatric ophthalmology, strabismus and neuro-ophthalmology practice in the COVID-19 era: All India Ophthalmological Society guidelines.

The COVID-19 Pandemic has prompted substantial changes in the way ophthalmology is practiced globally. General guidelines on safe ophthalmic practice have been issued by various bodies across the globe including the All India Ophthalmological Society. While these are suitable to ophthalmology overall, they are not entirely suitable to a subspecialty practice, particularly pediatric ophthalmology, strabismus and neuro-ophthalmology, which entails dealing with children, surgery under general anesthesia and managing possible life threatening situations. A group of sub-specialists and anesthetists met virtually and arrived at a consensus with regard to practice and general anesthesia protocols pertaining to these subspecialties of ophthalmology. The recommendations made by the expert group are specific yet can be universally followed to ensure the best and safest outcome for the practitioner and patient alike. The recommendations pertain to listing conditions which need emergency or urgent care in the fields of pediatric ophthalmology and neuro-ophthalmology, precautions and technique of pediatric and neuro-ophthalmic eye examination and a protocol for delivering a safe general anesthesia for a pediatriceye surgery.