Molecular markers for early stratification of disease severity and progression in COVID-19.

COVID-19 infections have imposed immense pressure on the healthcare system of most countries. While the initial studies have identified better therapeutic and diagnostic approaches, the disease severity is still assessed by close monitoring of symptoms by healthcare professionals due to the lack of biomarkers for disease stratification. In this study, we have probed the immune and molecular profiles of COVID-19 patients at 48-h intervals after hospitalization to identify early markers, if any, of disease progression and severity. Our study reveals that the molecular profiles of patients likely to enter the host-immune response-mediated moderate or severe disease progression are distinct even in the early phase of infection when severe symptoms are not yet apparent. Our data from 37 patients suggest that at hospitalization, interleukins (IL6) (>300 pg/ml) and IL8 levels (>200 pg/ml) identify cytokine-dependent disease progression. Monitoring their levels will facilitate timely intervention using available immunomodulators or precision medicines in those likely to progress due to cytokine storm and help improve outcomes. Additionally, it will also help identify cytokine-independent progressive patients, not likely to benefit from immunomodulators or precision drugs.

The effect of l-arginine supplementation on amelioration of oxygen support in severe COVID-19 pneumonia.

BACKGROUND & AIMS: l-Arginine (l-Arg) has been shown to help reduce respiratory support requirements in coronavirus disease 2019 (COVID-19), in an Italian study. We investigated the effect of l-Arg supplementation on the reduction in respiratory support for patients with severe COVID-19 pneumonia in an Indian population. METHODS: A parallel-group, triple-blinded, randomized controlled trial (RCT) was conducted on patients with severe COVID-19 pneumonia on oxygen (O2) support. Patients received either 3 g of oral l-Arg or placebo, daily under supervision, until they were off O2 support, or for a maximum of 10 days, whichever was earlier. The primary outcome was cessation in O2 support. Other outcomes were time to cessation of O2 support, duration of hospitalization, and incidence of adverse thrombotic events. RESULTS: We did an intention-to-treat analysis on 74 patients who were randomized into l-Arg (n = 38) or placebo group (n = 36). There were no significant differences between the two groups in the outcomes. At end of the study, 28 patients (73.6%) in l-Arg and 26 patients (72.2%) in the placebo group were weaned off oxygen support. The median number of days to the cessation of O2 support estimated using Kaplan Meir survival analysis, was 3 days in the l-Arg group (95% confidence interval [CI]: 1.2, 4.7) and 5 days in the placebo group (95% CI, 4.1,5.8); P = 0.27. CONCLUSION: In this group of patients with severe COVID-19 pneumonia, l-Arg supplementation did not show any significant difference in outcomes when compared to placebo supplementation.

A case of Post-COVID-19 thyrotoxicosis and a cavalcade of complications

Thyroid dysfunction has been reported following COVID-19 infection in the recent past. A 50 year old hypertensive female with no previous thyroid illness, developed features of thyrotoxicosis two weeks after a COVID-19 infection. There was no thyromegaly, neck pain or fever and her ESR was 15 mm/hour. She was initiated on propranolol and methimazole in an outside hospital. Ten days later, she presented to our hospital with fever, sore throat, cough and breathing difficulty. On evaluation she was found to be in neutropenic sepsis (WBC -820 cells/mm3, ANC-6 cells/mm3). Evaluation of thyroid functions showed: TSH- <0.00025 IU/ml, free T3 - 4.17 pg/ml, free T4- 3.59 ng/ml and Thyroid Receptor Antibody Levels (TRAb)- 2.53 IU/L. Following treatment with colony stimulating factors and antibiotics she recovered. The patient was commenced on lithium bicarbonate and cholestyramine, along with propranolol. On follow up in the OPD she is euthyroid with free T4 1.43 ng/ml (normal) levels. Post COVID-19 thyrotoxicosis in this case is likely due to Graves’ disease. Thyrotoxicosis following COVID-19 is now being recognised and is possibly due to infection induced molecular mimicry with activation of immune pathways causing autoimmune disorders.

Central obesity in low BMI as a risk factor for COVID-19 severity in South Indians.

BACKGROUND AND OBJECTIVES: South Asians are known to have excess adiposity at a lower body mass index, with truncal fat accumulation. Whether this confers higher risk to develop severe COVID-19 is not known. This study evaluated body mass index, body fat mass and waist circumference as risk factors for COVID-19 severity and its progression, in South Asian adults. METHODS AND STUDY DESIGN: Details of COVID-19 patients (19-90 years) were obtained prospectively, along with weight, height, waist circumference and body fat mass assessed by bioelectrical impedance analysis. Binomial logistic and Poisson regression were performed to test associations between waist circumference, body fat mass and body mass index to evaluate the adjusted OR or relative risk for disease severity at admission and length of stay. RESULTS: After adjusting for age, sex, height and co-morbidities, body mass index >23 kg/m2 (adjusted OR 2.758, 95% CI 1.025, 7.427), waist circumference (adjusted OR 1.047, 95% CI 1.002, 1.093) and body fat mass (adjusted OR 1.111, 95% CI 1.013, 1.219) were associated with a significant risk for disease severity at admission, while only waist circumference (adjusted relative risk 1.004, 95% CI 1.001, 1.008), and body fat mass (adjusted relative risk 1.011, 95% CI 1.003, 1.018), were associated with a significantly longer length of stay. CONCLUSIONS: Body mass index, at a lower cut-off of >23 kg/m2, is a significant risk factor for COVID-19 disease severity in the group of patients studied. The waist circumference and body fat mass are also good indicators for both severity at admission and length of stay.