Assessment of Neuroendocrine Changes and Hypothalamo-Pituitary Autoimmunity in Patients with COVID-19.

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.

Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1.

BACKGROUND: We aimed to establish an acute treatment protocol to increase serum vitamin D, evaluate the effectiveness of vitamin D3 supplementation, and reveal the potential mechanisms in COVID-19. METHODS: We retrospectively analyzed the data of 867 COVID-19 cases. Then, a prospective study was conducted, including 23 healthy individuals and 210 cases. A total of 163 cases had vitamin D supplementation, and 95 were followed for 14 days. Clinical outcomes, routine blood biomarkers, serum levels of vitamin D metabolism, and action mechanism-related parameters were evaluated. RESULTS: Our treatment protocol increased the serum 25OHD levels significantly to above 30 ng/mL within two weeks. COVID-19 cases (no comorbidities, no vitamin D treatment, 25OHD <30 ng/mL) had 1.9-fold increased risk of having hospitalization longer than 8 days compared with the cases with comorbidities and vitamin D treatment. Having vitamin D treatment decreased the mortality rate by 2.14 times. The correlation analysis of specific serum biomarkers with 25OHD indicated that the vitamin D action in COVID-19 might involve regulation of INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. CONCLUSIONS: Vitamin D treatment shortened hospital stay and decreased mortality in COVID-19 cases, even in the existence of comorbidities. Vitamin D supplementation is effective on various target parameters; therefore, it is essential for COVID-19 treatment.

COVID-19 healthcare cost and length of hospital stay in Turkey: retrospective analysis from the first peak of the pandemic.

BACKGROUND: During the COVID-19 pandemic, health care systems are under extreme pressure. This study analyzed health care resource use (HCRU) and costs in patients admitted to the hospital for COVID-19 and aimed to estimate the one-year direct medical cost of the disease in Turkey. METHODS: This retrospective cohort study was conducted between March and July 2020 in a tertiary hospital (n = 1056) in Istanbul. Patient demographics, clinical and treatment characteristics at admission, comorbidities, disease severity, and costs from a payer perspective were evaluated using the microcosting method. The results include LOS, hospital costs, and univariate and generalized linear models to investigate influencing factors. The data were extrapolated to provide a country-level estimate. RESULTS: The mean length of stay was 9.1 days (SD 6.9). The mean length of stay was 8.0 days (4.7) for patients hospitalized in wards versus 14.8 days (SD 12.0) for patients hospitalized in the ICU. In univariate analysis, several factors, including O2 therapy (+ 3.7 days), high CRP > 41.8 mg/L (+ 3.8 days), and elevated ferritin (+ 3.5), were found to be associated with a longer LOS (p < 0.05). The direct annual medical cost of COVID-19 was estimated at PPP$ 2.1 billion. The COVID-19 pandemic resulted in a direct medical burden that corresponds to 2.0% of the government health expenditures and 0.8 per thousand of Turkey's gross domestic product (GDP). CONCLUSIONS: Estimating the impact of this pandemic in terms of HCRU and costs to the health care system can help design strategies to manage the pandemic.

Cost-Effectiveness Analysis of Remdesivir Treatment in COVID-19 Patients Requiring Low-Flow Oxygen Therapy: Payer Perspective in Turkey.

INTRODUCTION: This study aims to evaluate the cost-effectiveness of remdesivir compared to other existing therapies (SoC) in Turkey to treat COVID-19 patients hospitalized with < 94% saturation and low-flow oxygen therapy (LFOT) requirement. METHODS: We compared remdesivir as the treatment for COVID-19 with the treatments in the Turkish treatment guidelines. Analyses were performed using data from 78 hospitalized COVID-19 patients with SpO2 < 94% who received LFOT in a tertiary healthcare facility. COVID-19 episode costs were calculated for 78 patients considering the cost of modeled remdesivir treatment in the same group from the payer's perspective. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) was calculated for remdesivir versus the SoC for the population identified. For Turkey, a reimbursement threshold value between USD 8599 (1 × per capita gross domestic product-GDP) and USD 25.797 (3 × GDP) per QALY was used. RESULTS: In the remdesivir arm, the length of hospital stay (LOS) was 3 days shorter than the SOC. The low ventilator requirement in the remdesivir arm was one factor that decreased the QALY disutility value. In patients who were transferred to intensive care unit (ICU) from the ward, the mean LOS was 17.3 days (SD 13.6), and the mean cost of stay was USD 155.3/day (SD 168.0), while in patients who were admitted to ICU at baseline, the mean LOS was 13.1 days (SD 13.7), and the mean cost of stay was USD 207.9/day (SD 133.6). The mean cost of episode per patient was USD 3461.1 (SD 2259.8) in the remdesivir arm and USD 3538.9 (SD 3296.0) in the SOC arm. Incremental QALYs were estimated at 0.174. Remdesivir treatment was determined to be cost saving vs. SoC. CONCLUSIONS: Remdesivir, which results in shorter LOS and lower rates of intubation requirements in ICU patients than existing therapies, is associated with higher QALYs and lower costs, dominating SoC in patients with SpO2 < 94% who require oxygen support.

The Role of Obesity in Predicting the Clinical Outcomes of COVID-19.

INTRODUCTION: The aim of this was to describe the predictors of mortality related to COVID-19 infection and to evaluate the association between overweight, obesity, and clinical outcomes of COVID-19. METHODS: We included the patients >18 years of age, with at least one positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction. Patients were grouped according to body mass index values as normal weight <25 kg/m2 (Group A), overweight from 25 to <30 kg/m2 (Group B), Class I obesity 30 to <35 kg/m2 (Group C), and ≥35 kg/m2 (Group D). Mortality, clinical outcomes, laboratory parameters, and comorbidities were compared among 4 groups. RESULTS: There was no significant difference among study groups in terms of mortality. Noninvasive mechanical ventilation requirement was higher in group B and D than group A, while it was higher in Group D than Group C (Group B vs. Group A [p = 0.017], Group D vs. Group A [p = 0.001], and Group D vs. Group C [p = 0.016]). Lung involvement was less common in Group A, and presence of hypoxia was more common in Group D (Group B vs. Group A [p = 0.025], Group D vs. Group A [p < 0.001], Group D vs. Group B [p = 0.006], and Group D vs. Group C [p = 0.014]). The hospitalization rate was lower in Group A than in the other groups; in addition, patients in Group D have the highest rate of hospitalization (Group B vs. Group A [p < 0.001], Group C vs. Group A [p < 0.001], Group D vs. Group A [p < 0.001], Group D vs. Group B [p < 0.001], and Group D vs. Group C [p = 0.010]). CONCLUSION: COVID-19 patients with overweight and obesity presented with more severe clinical findings. Health-care providers should take into account that people living with overweight and obesity are at higher risk for COVID-19 and its complications.