ABSTRACT
BACKGROUND: New onset hyperglycemia is common in patients with severe coronavirus disease 2019 (COVID-19) infection. Cytokine storm due to COVID-19 infection is an essential etiology for new-onset hyperglycemia, but factors like direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced pancreatic ß-cell failure have also been postulated to play a role. AIM: We plan to investigate further the mechanisms underlying SARS-CoV-2 infection-induced hyperglycemia, particularly the rationale of the cytokine-induced hyperglycemia hypothesis, by evaluating the association between inflammatory markers and new onset hyperglycemia in non-diabetic patients with COVID-19 infection. METHODS: We conducted a retrospective case-control study on adults without diabetes mellitus hospitalized for COVID-19 infection. The serum levels of glucose and inflammatory markers at presentation before initiation of corticosteroid were collected. Hyperglycemia was defined as glucose levels ≥ 140 mg/dL. C-Reactive protein (CRP) ≥ 100 mg/L, ferritin ≥ 530 ng/mL, lactate dehydrogenase (LDH) ≥ 590 U/L, and D-dimer ≥ 0.5 mg/L were considered elevated. We used the χ 2 test for categorical variables and the Mann-Whitney U test for continuous variables and calculated the logistic regression for hyperglycemia. RESULTS: Of the 520 patients screened, 248 met the inclusion criteria. Baseline demographics were equally distributed between patients with hyperglycemia and those who were normoglycemic. Serum inflammatory markers in patients with or without new-onset hyperglycemia were elevated as follows: CRP (58.1% vs 65.6%, P = 0.29), ferritin (48.4% vs 34.9%, P = 0.14), D-dimer (37.1% vs 37.1%, P = 0.76) and LDH (19.4% vs 11.8%, P = 0.02). Logistic regression analysis showed LDH odds ratio (OR) = 1.623 (P = 0.256). We observed significantly higher mortality (24.2% vs 9.1%, P = 0.001; OR = 2.528, P = 0.024) and length of stay (8.89 vs 6.69, P = 0.026) in patients with hyperglycemia. CONCLUSION: Our study showed no association between CRP, ferritin, LDH, D-dimer levels, and new-onset hyperglycemia in non-diabetic patients with COVID-19 infection. It also shows an increased mortality risk and length of stay in patients with hyperglycemia. With new-onset hyperglycemia being closely associated with poor prognostic indices, it becomes pivotal to understand the underlying pathophysiological mechanisms behind the SARS-CoV-2 infection-induced hyperglycemia. We conclude that the stress hyperglycemia hypothesis is not the only mechanism of SARS-CoV-2 infection-induced hyperglycemia but rather a multicausal pathogenesis leading to hyperglycemia that requires further research and understanding. This would help us improve not only the clinical outcomes of COVID-19 disease and inpatient hyperglycemia management but also understand the long-term effects of SARS-CoV-2 infection and further management.
ABSTRACT
Background: SARS-CoV-2 has been known to cause multisystemic involvement, gaining entry through ACE-2 and TMPRSS2 receptors. COVID-19 vaccine-associated thyroiditis cases are now being reported. Case Report. Case 1. A 36-year-old woman with a history of right hemithyroidectomy for a benign thyroid nodule, on a stable dose of levothyroxine with euthyroid labs, presented with progressively worsening left neck pain, episodic palpitations, and heat intolerance after the second dose of mRNA1273 (Moderna) vaccine. Examination revealed an enlarged and tender left lobe of the thyroid with suppressed TSH but normal free T4 and ESR, signifying subacute thyroiditis. She was managed conservatively without corticosteroids or beta-blockers, and her symptoms resolved. A follow-up revealed increasing TSH, and levothyroxine was restarted. Case 2. A 33-year-old man with a history of anxiety disorder on Sertraline, presented with a two-week history of palpitations, heat intolerance, and 10-pound weight loss after the second dose of BNT162b2 (Pfizer-BioNTech) vaccine. Examination revealed a normal thyroid gland with no tenderness with elevated thyroid peroxidase and thyroglobulin antibodies. Ultrasound showed a diffusely heterogeneous thyroid with increased vascularity, suggesting silent thyroiditis. Follow-up revealed a hypothyroid phase with high TSH for which levothyroxine supplementation was started. Discussion. COVID-19 vaccine-associated subacute and silent thyroiditis have occurred following all three kinds of available vaccines, characterized by an initial thyrotoxic phase, followed by a hypothyroid phase and a recovery phase. Hypotheses include an immune response triggering thyroid inflammation or cross-reactivity with viral proteins. Conclusions: COVID-19 vaccine-associated thyroiditis is rare, but long-term monitoring of these patients is essential to ensure appropriate diagnosis and management of the potential hypothyroid phase.