Hospital Outcomes in Patients Hospitalized for COVID-19 Pneumonia: The Effect of SARS-CoV-2 Vaccination and Vitamin D Status.

SARS-CoV-2 vaccination promises to improve outcomes for patients with COVID-19 pneumonia (most notably those with advanced age and at high risk for severe disease). Here, we examine serum 25-Hydroxyvitamin D (25(OH)D) status and outcomes in both old (>70 years) and young vaccinated (n = 80) and unvaccinated (n = 91) subjects, who were hospitalized due to COVID-19 pneumonia in a single center (Connolly Hospital Dublin). Outcomes included ICU admission and mortality. Serum 25(OH)D levels were categorized as D30 (<30 nmol/L), D40 (30-49.99 nmol/L) and D50 (≥50 nmol/L). In multivariate analyses, D30 was independently associated with ICU admission (OR: 6.87 (95% CI: 1.13-41.85) (p = 0.036)) and mortality (OR: 24.81 (95% CI: 1.57-392.1) (p = 0.023)) in unvaccinated patients, even after adjustment for major confounders including age, sex, obesity and pre-existing diabetes mellitus. While mortality was consistently higher in all categories of patients over 70 years of age, the highest observed mortality rate of 50%, seen in patients over 70 years with a low vitamin D state (D30), appeared to be almost completely corrected by either vaccination, or having a higher vitamin D state, i.e., mortality was 14% for vaccinated patients over 70 years with D30 and 16% for unvaccinated patients over 70 years with a 25(OH)D level greater than 30 nmol/L. We observe that high mortality from COVID-19 pneumonia occurs in older patients, especially those who are unvaccinated or have a low vitamin D state. Recent vaccination or having a high vitamin D status are both associated with reduced mortality, although these effects do not fully mitigate the mortality risk associated with advanced age.

Vitamin D Status and Mortality from SARS CoV-2: A Prospective Study of Unvaccinated Caucasian Adults.

COVID-19 and a low vitamin D state share common risk factors, which might explain why vitamin D deficiency has been linked with higher COVID-19 mortality. Moreover, measures of serum vitamin D may become lower during systemic inflammatory responses, further confounding the association via reverse causality. In this prospective study (recruited over 12 months), we examined whether the association between a low vitamin D state and in-hospital mortality due to SARS-CoV-2 pneumonia in unvaccinated subjects is explained by (i) the presence of shared risk factors (e.g., obesity, advanced age) or (ii) a reduction in serum 25(OH)D due to COVID-19 (i.e., reverse causality). In this cohort of 232 (mean age = 56 years) patients (all had SARS-CoV-2 diagnosed via PCR AND required supplemental oxygen therapy), we failed to find an association between serum vitamin D and levels of CRP, or other inflammatory markers. However, the hazard ratio for mortality for subjects over 70 years of age (13.2) and for subjects with a serum 25(OH)D level less than 30 nmol·L−1 (4.6) remained significantly elevated even after adjustment for gender, obesity and the presence of diabetes mellitus. Subjects <70 years and >70 years had significantly higher mortality with a serum 25(OH)D less than 30 nmol·L−1 (11.8% and 55%), than with a serum 25(OH)D greater than 30 nmol·L−1 (2.2% and 25%). Unvaccinated Caucasian adults with a low vitamin D state have higher mortality due to SARS CoV-2 pneumonia, which is not explained by confounders and is not closely linked with elevated serum CRP.

A case of pembrolizumab-induced severe DKA and hypothyroidism in a patient with metastatic melanoma.

Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy and improved outcomes for patients with advanced disease. Pembrolizumab, a monoclonal antibody that acts as a programmed cell death 1 (PD-1(PDCD1)) inhibitor, has been approved for the treatment of advanced melanoma and other solid tumours. Immune-related adverse events (irAEs) including endocrinopathies have been well described with this and other PD-1 inhibitors. While hypothyroidism and hyperthyroidism, and less commonly hypophysitis, are the most common endocrinopathies occurring in patients treated with pembrolizumab, the incidence of type 1 diabetes mellitus (T1DM) was low in clinical trials. We report a case of pembrolizumab-induced primary hypothyroidism and T1DM presenting with severe diabetic ketoacidosis (DKA). A 52-year-old male patient was treated with pembrolizumab for metastatic melanoma. He presented to the emergency department with a 1-day history of nausea and vomiting 2 weeks after his seventh dose of pembrolizumab, having complained of polyuria and polydipsia for 2 months before presentation. He had been diagnosed with thyroid peroxidase (TPO) antibody-negative hypothyroidism, requiring thyroxine replacement, shortly after his fifth dose. Testing revealed a severe DKA (pH: 6.99, glucose: 38.6 mmol/L, capillary ketones: 4.9 and anion gap: 34.7). He was treated in the intensive care unit as per the institutional protocol, and subsequently transitioned to subcutaneous basal-bolus insulin. After his diabetes and thyroid stabilised, pembrolizumab was recommenced to treat his advanced melanoma given his excellent response. This case highlights the importance of blood glucose monitoring as an integral part of cancer treatment protocols composed of pembrolizumab and other ICIs. Learning points: The incidence of T1DM with pembrolizumab treatment is being increasingly recognised and reported, and DKA is a common initial presentation. Physicians should counsel patients about this potential irAE and educate them about the symptoms of hyperglycaemia and DKA. The ESMO guidelines recommend regular monitoring of blood glucose in patients treated with ICIs, a recommendation needs to be incorporated into cancer treatment protocols for pembrolizumab and other ICIs in order to detect hyperglycaemia early and prevent DKA.