C allele of rs479200 of the host EGLN1 gene - a risk factor for severe COVID-19 (pilot study) (preprint)

Abstract Background Coronavirus disease-2019 (COVID-19) symptoms can range from asymptomatic, moderate to severe manifestations that result in an overall global case fatality rate of 2-7 %. While each variant has had it challenges, and some variants are more severe than others, risk factors of severe COVID-19 are still under investigation. In this context, the host genetic predisposition is also a crucial factor to investigate. In the present study, we investigated host genotypes of the SNP rs479200 of the host EGLN1 gene, previously implicated in high altitude pulmonary edema (HAPE), some of whose symptoms such as hypoxia profoundly overlap with severe COVID-19. Methods After informed consent, 158 RT-PCR confirmed COVID-19 patients (March 2020 to June 2021) were enrolled in the study. Based on their clinical manifestations, disease severity was categorized by the clinical team. Blood samples were drawn and DNA was extracted from the clot to infer different genotypes of the SNP rs479200 of the host EGLN1 gene. PCR-RFLP analysis of the SNP rs479200 (C > T) was performed with an amplicon size of 367 bp. Various genotypes (TT, TC and CC) were assigned based on the presence/absence of a restriction site (T/GTACA) for restriction enzyme BsrGI. Allele frequencies, Hardy-Weinberg Equilibrium (HWE) and multinomial logistic regression were performed using statistical tool SPSS version 23 (IBM). Findings We observed that the severe COVID-19 category was composed of comparatively younger patients with mean age (34.9), compared to asymptomatic and moderate categories whose mean age was 49.7 and 54.3, respectively. Preponderance of males and high heterozygosity (TC) was observed across the clinical categories. Notably, the frequency of C allele (0.664) was 2-fold higher than the T allele (0.336) in severe COVID-19 patients, whereas the allele frequencies were similar in asymptomatic and moderate category of COVID-19 patients. Multinomial logistic regression showed an association of genotypes with increasing clinical severity; odds ratio (adjusted OR- 11.414 (2.564-50.812)) and (unadjusted OR- 6.214 (1.84-20.99)) for the genotype CC in severe category of COVID-19. Interestingly, the TC genotype was also found to be positively associated with severe outcome (unadjusted OR-5.816 (1.489-22.709)), indicating association of C allele in imparting the risk of severe outcome. Interpretation The study provides strong evidence that the presence of C allele of SNP (rs479200) of the EGLN1 gene associates with severity in COVID-19 patients. Thus, the presence of C allele may be a risk factor for COVID-19 severity. This study opens new avenues towards risk assessment that include EGLN1 (rs479200) genotype testing and identifying patients with C allele who might be prioritized for critical care.

Outcomes of COVID-19 infection in patients with chronic kidney disease on maintenance hemodialysis at a COVID hospital in India (preprint)

BackgroundPatients with chronic kidney disease (CKD) on hemodialysis are highly vulnerable to COVID-19 infection with a mortality rate higher than the rest of the population. There are several clinical and laboratory parameters that can predict the course and the outcomes in this group of population. MethodsWe retrospectively collected the baseline demographic, clinical, in-hospital, and laboratory data of the patients with CKD on maintenance hemodialysis who were admitted to our COVID-19 hospital during the first and the second wave. ResultsWe obtained data for 35 patients from the first and 5 patients from the second wave. The analysis of the data for 35 patients from the first wave revealed shortness of breath (62.9%), and fever (54.3%) being the most common presenting symptoms, and the majority of the patients (57.2 %) presented with moderate to severe disease at admission with 57 % had bilateral lung infiltrates, and required oxygen support (65.7%) at admission. The comparison of clinical and laboratory markers between survivors (27 patients, 77.1%) and non-survivors (8 patients, 22.9%) revealed an older age, severe disease at presentation, invasive mechanical ventilation, baseline severe lymphocytopenia, high serum glutamic oxaloacetic transaminase, blood urea, and inflammatory markers like Interleukin-6 and procalcitonin, fibrinogen and low albumin in non survivors. ConclusionsThe older age, severe disease at presentation, the requirement of invasive mechanical ventilation, raised baseline Interleukin-6, procalcitonin, serum glutamic oxaloacetic transaminase, blood urea and a low albumin level could be valuable predictors of poor outcomes.

Molecular Hydrogen as an Adjuvant Therapy May be Associated with Increased Oxygen Saturation and Improved Exercise Tolerance In a COVID-19 patient (preprint)

COVID-19 is associated with respiratory failure and subsequent hypoxia. New therapies that reduce hypoxia are urgently needed. Molecular hydrogen (H2) therapy may reduce inflammation, oxidative stress, and hypoxia. This case report suggests that hydrogen-rich water (HRW) increases oxygen saturation increase exercise tolerance in a patient with COVID-19-like symptoms.

Coronavirus disease (COVID-19) associated Mucormycosis: An Anaesthesiologist's Perspective (preprint)

In India, the second wave of coronavirus disease (COVID -19) was associated with a distinct surge in cases of invasive fungal infection with mucormycosis. This disease was seen typically in the sinonasal form in COVID-19 patients. Uncontrolled diabetes, steroid use in COVID-19 treatment, etc. were some of the postulated risk factors for the association of COVID 19 and Mucormycosis. The management plan of these cases included surgical debridement, systemic antifungal therapy, sugar control, and management of antifungal related systemic adverse effects. In this retrospective case record review, we aimed to evaluate the airway management plan, demographics, and overall outcomes in patients undergoing surgical resection for COVID-19 associated mucormycosis. Forty-one (71.9 %) patients had a diagnosis of sino-nasal mucormycosis, fourteen (24.6%) had a diagnosis of rhino-orbital mucormycosis, and 2 patients (3.5%) were diagnosed with palatal mucormycosis. Total 44 (77.19 %) patients had co-morbidities. The most common co-morbidity was Diabetes Mellitus 42 (73.6%), followed by hypertension 21 (36.84%) and Acute kidney injury 14 (28.07%). We used the intubation difficulty scale score to assess intubating conditions. Intubation was easy to slightly difficult in 53 out of 57 patients. In our study, mortality occurred in 7 (12.28 %) patients. The median mortality time was 60 (range, 27-74) days. The median time to hospital discharge was 53.5 (range,10-85) days. Managing COVID-19 on its own is challenging and additional mucormycosis can lead to increased morbidity and mortality. Despite challenges and risks, timely and meticulous interventions can reduce complications.

Silent Hypoxia in Coronavirus disease-2019: Is it more dangerous?-A retrospective cohort study (preprint)

BackgroundHypoxia in patients with COVID-19 is one of the strongest predictors of mortality. Silent hypoxia is characterized by the presence of hypoxia without dyspnea.. Silent hypoxia has been shown to affect the outcomes in previous studies. Research QuestionAre the outcomes in patients presenting with silent hypoxia different from those presenting with dyspneic hypoxia? Study design and MethodsThis was a retrospective study of a cohort of patients with SARS-CoV-2 infection who were hypoxic at presentation. Clinical, laboratory, and treatment parameters in patients with silent hypoxia and dyspneic hypoxia were compared. Multivariate logistic regression models were fitted to identify the factors predicting mortality. ResultsAmong 2080 patients with COVID-19 admitted to our hospital, 811 patients were hypoxic with SpO2<94% at the time of presentation. 174 (21.45%) did not have dyspnea since the onset of COVID-19 symptoms. 5.2% of patients were completely asymptomatic for COVID-19 and were found to be hypoxic only on pulse oximetry. The case fatality rate in patients with silent hypoxia was 45.4% as compared to 40.03% in dyspneic hypoxic patients (P=0.202). The odds ratio of death was 1.1 (95% CI 0.41-2.97) in the patients with silent hypoxia after adjusting for baseline characteristics, laboratory parameters, treatment, and in-hospital complications, which did not reach statistical significance (P=0.851). InterpretationSilent hypoxia may be the only presenting feature of COVID-19. Since the case fatality rate is comparable between silent and dyspneic hypoxia, it should be recognized early and treated as aggressively. Since home isolation is recommended in patients with COVID-19, it is essential to use pulse oximetry at the home setting to identify these patients.

Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India-A cohort study (preprint)

Background The second wave of the COVID-19 pandemic hit India from early April 2021 to June 2021 and more than 400,000 cases per day were reported in the country. We describe the clinical features, demography, treatment trends, baseline laboratory parameters of a cohort of patients admitted at the All India Institute of Medical Sciences, New Delhi with SARS-CoV-2 infection and their association with the outcome. Methods This was a retrospective cohort study describing the clinical, laboratory and treatment patterns of consecutive patients admitted with SARS-CoV-2 infection. Multivariate logistic regression models were fitted to identify the clinical and biochemical predictors of developing hypoxia, deterioration during the hospital stay and death. Findings A total of 2080 patients were included in the study. The case fatality rate was 19.5%. Amongst the survivors, the median duration of hospital stay was 8 (5-11) days. Out of 853 (42.3%%) of patients who had COVID-19 Acute respiratory distress syndrome at presentation, 340 (39.9%) died. Patients aged 45-60 years [OR (95% CI): 1.8 (1.2-2.6)p =0.003] and those aged >60 years [OR (95%CI): 3.4 (2.3-5.2), p<0.001] had a higher odds of death as compared to the 18-44 age group. Vaccination reduced the odds of death by 30% [OR (95% CI): 0.7 (0.5-0.9), p=0.036]. Patients with hyper inflammation at baseline as suggested by leucocytosis [OR (95% CI): 2.1 (1.4-3.10), p <0.001], raised d-dimer >500 mg/dL [OR (95% CI): 3.2 (2.2-4.6), p <0.001] and raised C-reactive peptide >0.5 mg/L [OR (95% CI): 3.8 (1.1-13), p=0.037] had higher odds of death. Patients who were admitted in the second week had lower odds of death and those admitted in the third week had higher odds of death. Interpretation This is the largest cohort of patients admitted with COVID-19 from India reported to date and has shown that vaccination status and early admission during the inflammatory phase can change the course of illness of these patients. Strategies should be made to improve vaccination rates and early admission of patients with moderate and severe COVID-19 to improve outcomes. Research in context Evidence before this study The COVID-19 pandemic has been ravaging the world since December 2019 and the cases in various regions are being reported in waves. We found that the case fatality rates ranging from 1.4% to 28.3% have been reported in the first wave in India. Older age and the presence of comorbidities are known predictors of mortality. There are no reports regarding the effectiveness of vaccination, correlation of mortality with the timing of admission to the health care facility and inflammatory markers in the ‘second wave’ of the COVID-19 pandemic in India. Added-value of this study This study reports the real-world situation where patients get admitted at varying time points of their illness due to the mismatch between the availability of hospital beds and the rising number of COVID-19 patients during the pandemic. It reports the odds of developing severe hypoxia necessitating oxygen therapy and death thus helping identify priority groups for admission. Implications of all the available evidence This study found increased odds of requiring oxygen support or death in patients older than 45 years of age, with comorbidities, and those who had hyper-inflammation with raised C-reactive peptide, d-dimer or leukocytosis. Patients who were admitted in the second week of illness had lower odds of death as compared to those admitted in the third week implying that treatment with corticosteroids in the second week of the illness during the ‘inflammatory phase’ could lead to reduced mortality. These findings would help triage patients and provide guidance for developing admission policy during times where hospital beds are scarce. Vaccination was found to reduce the odds of deterioration or death and should be fast-tracked to prevent further ‘waves’ of the pandemic.

Impact of COVID-19 Lockdown on the Fisheries Sector: A Case Study from Three Harbors in Western India

The COVID-19 related lockdowns have brought the planet to a standstill. It has severely shrunk the global economy in the year 2020, including India. The blue economy and especially the small-scale fisheries sector in India have dwindled due to disruptions in the fish catch, market, and supply chain. This research presents the applicability of satellite data to monitor the impact of COVID-19 related lockdown on the Indian fisheries sector. Three harbors namely Mangrol, Veraval, and Vankbara situated on the north-western coast of India were selected in this study based on characteristics like harbor’s age, administrative control, and availability of cloud-free satellite images. To analyze the impact of COVID in the fisheries sector, we utilized high-resolution PlanetScope data for monitoring and comparison of “area under fishing boats”during the pre-lockdown, lockdown, and post-lockdown phases. A support vector machine (SVM) classification algorithm was used to identify the area under the boats. The classification results were complemented with socio-economic data and ground-level information for understanding the impact of the pandemic on the three sites. During the peak of the lockdown, it was found that the “area under fishing boats”near the docks and those parked on the land area increased by 483%, 189%, and 826% at Mangrol, Veraval, and Vanakbara harbor, respectively. After phase-I of lockdown, the number of parked vessels decreased, yet those already moved out to the land area were not returned until the south-west monsoon was over. A quarter of the annual production is estimated to be lost at the three harbors due to lockdown. Our last observation (September 2020) result shows that regular fishing activity has already been re-established in all three locations. PlanetScope data with daily revisit time has a higher potential to be used in the future and can help policymakers in making informed decisions vis-à-vis the fishing industry during an emergency situation like COVID-19.

Entomological survey of vectors of scrub typhus in Haulawng, Lunglei district, Mizoram, India. (Special issue on COVID-19.)

A study on the vector prevalence of Scrub typhus was undertaken in the Scrub typhus affected areas in Lunglei district, Mizoram. Rodents were trapped using live traps and examined for ectoparasites and serological test for scrub typhus antibodies was also done. Results on the vectors of the Scrub typhus revealed the presence of the vector mite Leptotrombidium deliense on the rats in 3 localities of Haulawng village. Chigger index was found to be 12.33, which is above the critical index of 0.69 per rodent. Chigger infestation rate was 18.5. The chigger infestation was found mainly on Rattus rattus. Detection of Orientia (Scrub typhus) 1:20 and 1:80 has been calculated by Weil Felix OXK antigen. Observation of the vector of Scrub typhus warrants regular surveillance in these areas to prevent any impending outbreak.

COVID-19 and Contractual Disputes in India (preprint)

The COVID-19 pandemic has unleashed a catena of contractual disputes. Several companies and firms have cited COVID-19 as force majeure to suspend the promised supply of goods or services, triggering legal claims of compensation from the counterparties. Employers have refused the promised employment, borrowers have expressed their inability to service debts, and insurance companies have denied compensation for business losses. Even the Centre is wavering in honoring terms of the ‘social contract’ for sharing GST revenue with the States.In this article, we synthesise the Indian Contract Act and relevant case laws to present a legal position on force majeure, frustration of contract and contractual gaps. Using the economic analysis of law, we examine contractual disputes from various sectors, including power, construction and real-estate, rental, event management and hospitality, among others. We analyse these disputes from legal and economic-efficiency points of view. We delineate disputes where the use of force majeure or frustration of contract is justified. We use economic analysis to draw the attention of courts and policymakers towards the economic implication of their decisions. Our analysis suggest that at times the courts under-appreciate the long-term economic consequences of their rulings. Finally, we argue that contracts are not a good instrument for achieving equitable distribution of economic gains and losses. We discuss how public policy is better suited to address equity the other related issues arising from long-term contracts such as debt, employment and insurance contracts.