Subacute thyroiditis following recovery from COVID-19 infection: novel clinical findings from an Eastern Indian cohort.

OBJECTIVE: Recent reports have suggested a link between COVID-19 infection and subacute thyroiditis (SAT). We aimed to describe variations in clinical and biochemical parameters in patients developing post-COVID SAT. DESIGN: Ours was a combined retrospective-prospective study on patients presenting with SAT within 3 months of recovery from COVID-19 infection, who were subsequently followed up for a further 6 months since diagnosis of SAT. RESULTS: Out of 670 patients with COVID-19, 11 patients presented with post-COVID-19 SAT (6.8%). Those with painless SAT (PLSAT, n = 5) presented earlier, had more severe thyrotoxic manifestations and exhibited higher C-reactive protein, interleukin 6 (IL-6), neutrophil-lymphocyte ratio and lower absolute lymphocyte count than those with painful SAT (PFSAT, n = 6). There were significant correlations of total and free T4 and total and free T3 levels with serum IL-6 levels (pall <0.04). No differences were observed between patients with post-COVID SAT presenting during the first and second waves. Oral glucocorticoids were needed for symptomatic relief in 66.67% of patients with PFSAT. At 6 months of follow-up, majority (n = 9, 82%) achieved euthyroidism, while subclinical and overt hypothyroidism were found in one patient each. CONCLUSIONS: Ours is the largest single-centre cohort of post-COVID-19 SAT reported until, demonstrating two distinct clinical presentations-without and with neck pain-depending on time elapsed since COVID-19 diagnosis. Persistent lymphopaenia during the immediate post-COVID recovery period could be a key driver of early,painless SAT. Close monitoring of thyroid functions for at least 6 months is warranted in all cases.

A Prospective Characterization of Metabolic and Metabolomic Profiles of COVID-19–Associated New-Onset Diabetes Patients Presenting with DKA from India

Background: Recent evidence suggests a bidirectional relationship between COVID-infection and new-onset diabetes (NOD) presenting with DKA. Methodology: This one-year prospective study comprised of 29 COVID-negative DKA (controls) and 52 COVID-positive-DKA patients (18 NOD, 15 T1DM ,T2DM) . NOD were previously normoglycemic and negative for GAD/IA-2/ZnT8 autoantibodies. After 75g- OGTT with estimation of glucose, C-peptide, FFA and insulin at 0,15, 30,45, 60,90 ,120, 150 and 180minutes, Insulin secretion rate (ISR) [C-peptide-deconvolution] , Hepatic insulin sensitivity [AUC-glucose × AUC-insulin during first 30-minutes of OGTT ], Peripheral insulin sensitivity [ dG/dt ÷ mean plasma insulin concentration;dG/dt rate of decline in plasma glucose concentration]were calculated alongwith Metabolomics and Adipose tissue gene expression. All tests were performed at admission and 4, 8, and 12-months of followup. Results: At baseline, ISR in NOD was significantly reduced than controls (p=0.001) but similar to T1DM (p=0.15) . Nearly 83% (n=17) of NOD with DKA had near-complete recovery of ISR on follow-up compared to T1DM (all p<0.01) ,with non-remitters (n=3) having significantly worse admission Hba1c and IL-6 (all p<0.01) . NOD had significantly increased hepatic and peripheral insulin resistance compared to T1DM (all p<0.05) ,but similar to T2DM (all p>0.05) . Their Metabolomics revealed increased inflammatory phosphatidylcholines, that correlated with peripheral glucose uptake (p<0.01) ,while RNA sequencing showed significantly enhanced WNT5A , TLR4 (Toll-like Receptor-4) and RETN (resistin) than T1DM and T2DM (both p=0.001) . Conclusion: Our study provides novel insights into COVID-associated NOD with DKA. Majority have near-complete recovery of insulin secretion while simultaneous multi-tissue insulin resistance and inflammatory adipose tissue profiles persist as drivers of hyperglycemia.

Stress hyperglycemia ratio, rather than admission blood glucose, predicts in-hospital mortality and adverse outcomes in moderate-to severe COVID-19 patients, irrespective of pre-existing glycemic status.

AIM: To compare admission-blood-glucose (ABG) or stress-hyperglycemia-ratio (SHR) performs better in predicting mortality and worse outcomes in COVID-19 patients with (DM) and without known Type 2 Diabetes Mellitus (UDM). METHODS: ABG and SHR were tested for 451 patients with moderate-severe COVID-19 infection [DM = 216,47.9%; pre-diabetes = 48,10.6%, UDM = 187,41.4%],who were followed-up to look for in-hospital-mortality (primary outcome) and secondary outcomes (ICU stay or mechanical ventilation, hospital-acquired-sepsis and multiple organ dysfunction syndrome [MODS]). Those with and without SHR ≥ 1.14 were compared; logistic regression was done to identify predictors of outcomes, with subgroup analysis based on pre-existing DM status and COVID-19 severity. RESULTS: Those who died (n = 131) or developed ≥ 1 secondary outcomes (n = 218) had higher prevalence of SHR ≥ 1.14, ABG ≥ 180 mg/dl and higher median SHR (pall < 0.01). Those with SHR ≥ 1.14 had higher mortality (53.7%), higher incidence of ≥ 1 secondary outcomes (71.3%) irrespective of pre-existing diabetes status. SHR ≥ 1.14, but not ABG ≥ 180 was an independent predictor of mortality in the whole group (OR: 7.81,4.07-14.98), as also the DM (OR:10.51,4.34-25.45) and UDM (5.40 (1.57-18.55) subgroups. SHR ≥ 1.14 [OR: 4.41 (2.49-7.84)] but not ABG ≥ 180 could independently predict secondary outcomes AUROC of SHR in predicting mortality was significantly higher than ABG in all subgroups. CONCLUSION: SHR better predicts mortality and adverse outcomes than ABG in patients with COVID-19, irrespective of pre-existing chronic glycemic status.

Subacute thyroiditis following recovery from COVID-19 infection: novel clinical findings from an Eastern Indian cohort.

OBJECTIVE: Recent reports have suggested a link between COVID-19 infection and subacute thyroiditis (SAT). We aimed to describe variations in clinical and biochemical parameters in patients developing post-COVID SAT. DESIGN: Ours was a combined retrospective-prospective study on patients presenting with SAT within 3 months of recovery from COVID-19 infection, who were subsequently followed up for a further 6 months since diagnosis of SAT. RESULTS: Out of 670 patients with COVID-19, 11 patients presented with post-COVID-19 SAT (6.8%). Those with painless SAT (PLSAT, n = 5) presented earlier, had more severe thyrotoxic manifestations and exhibited higher C-reactive protein, interleukin 6 (IL-6), neutrophil-lymphocyte ratio and lower absolute lymphocyte count than those with painful SAT (PFSAT, n = 6). There were significant correlations of total and free T4 and total and free T3 levels with serum IL-6 levels (pall <0.04). No differences were observed between patients with post-COVID SAT presenting during the first and second waves. Oral glucocorticoids were needed for symptomatic relief in 66.67% of patients with PFSAT. At 6 months of follow-up, majority (n = 9, 82%) achieved euthyroidism, while subclinical and overt hypothyroidism were found in one patient each. CONCLUSIONS: Ours is the largest single-centre cohort of post-COVID-19 SAT reported until, demonstrating two distinct clinical presentations-without and with neck pain-depending on time elapsed since COVID-19 diagnosis. Persistent lymphopaenia during the immediate post-COVID recovery period could be a key driver of early,painless SAT. Close monitoring of thyroid functions for at least 6 months is warranted in all cases.

Predictors of new-onset diabetic ketoacidosis in patients with moderate to severe COVID-19 receiving parenteral glucocorticoids: A prospective single-centre study among Indian type 2 diabetes patients.

BACKGROUND AND AIM: COVID-19 infection predisposes to diabetic ketoacidosis(DKA); whether glucocorticoids enhances this risk is unknown.We aimed to study the occurrence of DKA after initiating glucocorticoids in patients with type 2 diabetes mellitus(T2DM) and moderate-to-severe COVID-19, and identify predictors for it. METHODS: Patients with T2DM and moderate or severe COVID-19 infection were prospectively observed for development of new-onset DKA for one week following initiation of parenteral dexamethasone. Clinical and biochemical parameters were compared between those who developed DKA (Group A) and those who didnot (Group B). Logistic regression was done to identify independent risk-factors predicting DKA; ROC-curve analysis to determine cut-offs for the parameters in predicting DKA. RESULTS: Amongst 302 patients screened, n = 196 were finally included, of whom 13.2% (n = 26,Group A) developed DKA. Patients in Group A were younger, had lower BMI, increased severity of COVID-19 infection, higher HbA1c%, CRP, IL-6, D-dimer and procalcitonin at admission (pall < 0.02). Further, admission BMI (OR: 0.43, CI: 0.27-0.69), HbA1c % (OR: 1.68, CI: 1.16-2.43) and serum IL-6 (OR: 1.02, CI: 1.01-1.03) emerged as independent predictors for DKA. Out of these, IL-6 levels had the highest AUROC (0.93, CI: 0.89-0.98) with a cut-off of 50.95 pg/ml yielding a sensitivity of 88% and specificity of 85.2% in predicting DKA. CONCLUSION: There is significant incidence of new-onset DKA following parenteral glucocorticoids in T2DM patients with COVID-19, especially in those with BMI <25.56 kg/m2, HbA1c% >8.35% and IL-6 levels >50.95 pg/ml at admission.

Managing diabetic foot in times of COVID-19: time to put the best 'foot' forward.

INTRODUCTION: The COVID-19 pandemic has had an unparalleled impact on the socio-economic and healthcare structure of India. Due to our large populations of diabetic patients, who have an increased risk of worse outcomes with COVID-19 infection, it is of utmost public health importance to analyse the relationship between the two. The aim of our review was to analyse the possible relationship between COVID-19 infection and DFUs, which are a fairly common, yet serious complication in diabetic patients, as well as their management, under the given changing circumstances. METHODOLOGY: An extensive review of related educational articles was analysed from various databases. RESULTS: The two main pathogenic mechanisms described in COVID-19 infection are a cytokine storm (causing ARDS) as well as an acquired coagulopathy, with widespread thrombosis. DFUs are associated with an underlying peripheral neuropathy, a chronic low-grade inflammatory state and peripheral arterial disease, which lead to chronic non-healing ulcers. Similarities seen in the pathogenic mechanisms of these two conditions make a bidirectional relationship highly plausible. CONCLUSION: Due to the disruptions in the healthcare system brought on by the COVID-19 pandemic, changes in practice to a telehealth-driven approach, with emphasis on homecare and community clinics, need to be adopted, to ensure best possible care to patients with DFUs, in order to reduce their risk of DFU-related complications and need for hospitalization.