Association of Vitamin D Status With Hospital Morbidity and Mortality in Adult Hospitalized Patients With COVID-19

ObjectiveTo determine the association between vitamin D status and morbidity and mortality in adult hospitalized coronavirus disease 2019 (COVID-19) patientsMethodsWe performed a retrospective chart review study in COVID-19 patients aged ≥18 year hospitalized at Boston University Medical Center between March 1 and August 4, 2020. All studied patients tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D (25[OH]D) results measured within 1 year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and was analyzed to determine the association between vitamin D status and hospital morbidity and mortality.ResultsAmong the 287 patients, 100 (36%) were vitamin D sufficient (25[OH]D >30 ng/mL) and 41 (14%) died during hospitalization. Multivariate analysis in patients aged ≥65 years revealed that vitamin D sufficiency (25[OH]D ≥30 ng/mL) was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95% CI, 0.12-0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95% CI, 0.05-0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95% CI, 0.08-0.88), after adjustment for potential confounders. Among patients with body mass index <30 kg/m², vitamin D sufficiency was statistically significantly associated with a decreased odds of death (adjusted OR 0.18, 95% CI, 0.04-0.84). No significant association was found in the subgroups of patients aged <65 years or with body mass index ≥30 kg/m².ConclusionWe revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.     

Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19

ObjectiveTo explore the relationship between hyperglycemia in the presence and absence of diabetes mellitus (DM) and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsThe study included 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an urban academic quaternary-care center between March 10 and April 8, 2020. Patients were categorized based on the presence or absence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first 2 days after ICU admission. The primary outcome was 14-day all-cause in-hospital mortality; also examined were 60-day all-cause in-hospital mortality and the levels of C-reactive protein, interleukin 6, procalcitonin, and lactate.ResultsCompared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HRs) for mortality at 14 days (HR 7.51, CI 1.70-33.24) and 60 days (HR 6.97, CI 1.86-26.13). Non-DM patients with EHG also featured higher levels of median C-reactive protein (306.3 mg/L, P = .036), procalcitonin (1.26 ng/mL, P = .028), and lactate (2.2 mmol/L, P = .023).ConclusionAmong critically ill COVID-19 patients, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. Our study was limited by its retrospective design and relatively small cohort. However, our results suggest the combination of elevated glucose and lactate may identify a specific cohort of individuals at high risk for mortality from COVID-19. Glucose testing and control are important in individuals with COVID-19, even those without preexisting diabetes.     

COVID-19 May Increase the Risk of Insulin Resistance in Adult Patients Without Diabetes: A 6-Month Prospective Study

ObjectiveDuring the coronavirus disease 2019 (COVID-19) pandemic, exploring insulin resistance and beta-cell activity is important for understanding COVID-19‒associated new-onset diabetes. We assessed insulin sensitivity and fasting insulin secretion in patients with COVID-19 without diabetes on admission and at 3 and 6 months after discharge.MethodsThis 6-month prospective study assessed data from the records of 64 patients without diabetes diagnosed with COVID-19 at Wenzhou Central Hospital, China. Each patient was followed up at 3 and 6 months after discharge. Repeated measures analysis of variance was used to investigate differences in multiple measurements of the same variable at different times. Linear regression analysis was performed to analyze the contributor for changes in the triglyceride-glucose (TyG) index.ResultsFasting C-peptide levels in patients at baseline were lower than the normal range. Compared with the baseline results, patients had significantly elevated fasting C-peptide levels (0.35 ± 0.24 vs 2.36 ± 0.98 vs 2.52 ± 1.11 μg/L; P < .001), homeostasis model assessment for beta-cell function (0.42, interquartile range [IQR] 0.36-0.62 vs 2.54, IQR 1.95-3.42 vs 2.90, IQR 2.02-4.23; P < .001), and TyG indices (8.57 ± 0.47 vs 8.73 ± 0.60 vs 8.82 ± 0.62; P = .006) and decreased fasting glucose levels (5.84 ± 1.21 vs 4.95 ± 0.76 vs 5.40 ± 0.68 mmol/L; P = .003) at the 3- and 6-month follow-up. Male gender, age, interferon-alfa treatment during hospitalization, and changes in total cholesterol and high-density lipoprotein levels were significantly associated with changes in the TyG index.ConclusionOur study provided the first evidence that COVID-19 may increase the risk of insulin resistance in patients without diabetes.     

Low Diagnostic Utility of Overnight High-Dose Dexamethasone Suppression Test in ACTH-Dependent Cushing’s Syndrome

ObjectiveOvernight high-dose dexamethasone suppression test (ON-HDDST) is a simple test to localize the source of ACTH in patients with ACTH-dependent Cushing’s syndrome (CS). However, previous studies have reported its varying accuracy. We studied the utility of ON-HDDST in diagnosing Cushing’s disease (CD) in a series of patients with CD and ectopic ACTH syndrome (EAS).MethodsWe conducted a retrospective study of 88 patients with ACTH-dependent CS (plasma ACTH > 20.0 pg/mL), who underwent an ON-HDDST. CD and EAS were diagnosed in 68 and 20 patients, respectively. Patients were investigated using MRI of the sellar region, CT of the thorax/abdomen, Gallium-68-DOTANOC PET scan, and bilateral inferior petrosal sinus sampling as required.ResultsPatients with EAS had a significantly higher serum cortisol after ON-HDDST than patients with CD (median [IQR], 19.9 [12.4-31.1] μg/dL vs 9.9 [5.1-25.0] μg/dL, P <.01). A suppressed ON-HDDST (≥50% fall from baseline) was noted in 44 (65%) patients with CD and 3 (15%) patients with EAS (P <.0001). Among patients with CD, cortisol suppression >50% was noted in 35 (76%) of patients with microadenoma and 7 (44%) with macroadenoma. Among patients with EAS, ON-HDDST was suppressed in 1 of 6 patients (17%) with an occult tumor and 2 of 14 patients (14%) with a localized tumor. The ROC curve plotted for the percentage suppression of cortisol had an area under the curve (AUC) of 0.72 (P =.01). The best test parameters, with 65% sensitivity, 85% specificity, 94% positive predictive value, 42% negative predictive value, and 69% accuracy, were at 50% cutoff level.ConclusionThe ON-HDDST had a poor diagnostic value in differentiating CD and EAS.     

Long COVID in Patients With Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?

ObjectivePost-acute sequelae of coronavirus disease 2019 (COVID-19) or long COVID (LC) is an emerging global health issue. Fatigue is a common feature. Whether thyroid function and autoimmunity play a role is uncertain. We aimed to evaluate the prevalence and predictors of LC and the potential role of thyroid function and autoimmunity in LC.MethodsWe included consecutive adults without a known thyroid disorder who were admitted to a major COVID-19 center for confirmed COVID-19 from July to December 2020. Thyroid function tests and antithyroid antibodies were measured for all patients on admission and at follow-up. LC was defined by the presence or persistence of symptoms upon follow-up.ResultsIn total, 204 patients (median age, 55.0 years; 95 men [46.6%]) were reassessed at a median of 89 days (interquartile range, 69-99) after acute COVID-19. Of the 204 patients, 41 (20.1%) had LC. Female sex (adjusted odds ratio, 2.48; P = .018) and severe acute respiratory syndrome coronavirus 2 polymerase chain reaction cycle threshold value of <25 on admission (adjusted odds ratio, 2.84; P = .012) independently predicted the occurrence of LC. Upon follow-up, most abnormal thyroid function tests in acute COVID-19 resolved, and incident thyroid dysfunction was rare. Nonetheless, we observed incident antithyroid peroxidase (anti-TPO) positivity. Although baseline or follow-up thyroid function tests were not associated with the occurrence of LC, among 172 patients with symptomatic acute COVID-19, symptom resolution was more likely in those with positive anti-TPO upon follow-up (P = .043).ConclusionLC is common among COVID-19 survivors, with females and those with higher viral load in acute COVID-19 particularly being vulnerable. The observation of incident anti-TPO positivity warrants further follow-up for thyroid dysfunction. Whether anti-TPO plays a protective role in LC remains to be elucidated.     

Vitamin D and Its Potential Benefit for the COVID-19 Pandemic

Vitamin D is known not only for its importance for bone health but also for its biologic activities on many other organ systems. This is due to the presence of the vitamin D receptor in various types of cells and tissues, including the skin, skeletal muscle, adipose tissue, endocrine pancreas, immune cells, and blood vessels. Experimental studies have shown that vitamin D exerts several actions that are thought to be protective against coronavirus disease (COVID-19) infectivity and severity. These include the immunomodulatory effects on the innate and adaptive immune systems, the regulatory effects on the renin-angiotensin-aldosterone-system in the kidneys and the lungs, and the protective effects against endothelial dysfunction and thrombosis. Prior to the COVID-19 pandemic, studies have shown that vitamin D supplementation is beneficial in protecting against risk of acquiring acute respiratory viral infection and may improve outcomes in sepsis and critically ill patients. There are a growing number of data connecting COVID-19 infectivity and severity with vitamin D status, suggesting a potential benefit of vitamin D supplementation for primary prevention or as an adjunctive treatment of COVID-19. Although the results from most ongoing randomized clinical trials aiming to prove the benefit of vitamin D supplementation for these purposes are still pending, there is no downside to increasing vitamin D intake and having sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at a level of least 30 ng/mL (75 nmol/L) and preferably 40 to 60 ng/mL (100-150 nmol/L) to minimize the risk of COVID-19 infection and its severity.     

Assessment of the Effectiveness of a Protocol to Manage Dexamethasone-Induced Hyperglycemia Among Hospitalized Patients With COVID-19

ObjectiveWell-controlled glucose levels (ie, 70-180 mg/dL) have been associated with lower mortality from COVID-19. The addition of dexamethasone to COVID-19 treatment protocols has raised concerns about the potential negative consequences of dexamethasone-induced hyperglycemia.MethodsWe developed a protocol to guide the management of dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19. Two of the 4 medical teams managing patients with COVID-19 at a tertiary center in Saudi Arabia used the protocol and the other 2 teams continued to manage hyperglycemia at the discretion of the treating physicians (protocol and control groups, respectively). The glycemic control and clinical outcomes in 163 patients hospitalized with COVID-19 and dexamethasone-induced hyperglycemia between July 5th and September 30th, 2020, were retrospectively compared between the 2 groups.ResultsCompared to the control group, the protocol group had higher proportions of patients with well-controlled glucose across all premeals and bedtime glucose readings throughout the hospital stay. The differences in glycemic control between the 2 groups were statistically significant for fasting glucose on days 4, 5, and the discharge day; prelunch glucose on the discharge day; predinner glucose on days 3, 5, and the discharge day; and bedtime glucose on day 1 (all P < .05). After adjusting for age, sex, nationality, body mass index, Charlson score, and diabetes status, patients in the protocol group were more likely to have well-controlled glucose levels compared with those in the control group. Moreover, the in-hospital mortality was significantly lower in the protocol group (12.93%) compared to the control group (29.93%) (P < .01).ConclusionThe implementation of a protocol to manage dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19 resulted in more patients achieving well-controlled glucose levels and was associated with lower mortality from COVID-19.     

Post-COVID-19 effect on biochemical parameters in children: Should we take heed?

The aim of this research is to analyze the potential impact of the COVID-19 infection on the serum biochemical concentration of children 6 months after recovery from the infection.The study included 72 children with a median age of 11 years. The case group consisted of 37 children who had contracted COVID-19 6 months prior to the analysis. They reported no other pre- or post-covid chronic or systemic diseases. The control group consisted of 35 children who had no prior record of COVID-19 infection.The analysis showed a substantial variation (P = 0.026) in the mean urea values (mmol/L) between the case group (4.513 ± 0.839) and the control group (5.425 ± 1.173). However, both groups' urea levels were within the normal range of their age group. No statistical differences were found analyzing the variations between the two groups in the levels of LDH, AST, ALT, BiliT, GGT, AlbBCG2, CRP, CK, AlKP, UA, Phos, Crea2, Gluc, Ca, Na, K, Cl, TP, TC, TG, and HDL (P > 0.05). The DMFT score was substantially greater (P < 0.002) in the infected team (5.38 ± 2.841) in comparison to the non-infected group (2.6 ± 2.257).The study indicates that COVID-19 infection does not leave biochemical alterations among children who did not have pre-existing conditions. The biochemical analysis suggests that children recover better than adults from COVID-19. Furthermore, it calls for investigating non-lethal COVID-19 infection as a tool to discover underlying conditions. The DMFT score shows a correlation between COVID-19 infection and caries. However, the nature of the correlation is yet to be investigated.     

Etiology-, Sex-, and Tumor Size-Based Differences in Adrenocorticotropin-Dependent Cushing Syndrome

ObjectiveTo examine demographic, clinical, and biochemical differences in patients with adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS) based on etiology, sex, and tumor size.MethodsThis was a single-center study of 211 patients with ACTH-dependent CS followed for 35 years. Patients were stratified into 3 groups based on etiology: Cushing disease (CD)/transsphenoidal surgery, Cushing disease/total bilateral adrenalectomy (CD/TBA), and ectopic ACTH secretion (EAS). Patients were also stratified based on sex and tumor size (nonvisualized, microadenoma, and macroadenoma).ResultsCD was the commonest cause of ACTH-dependent CS (190; 90%). Most patients presented in the third decade (median age, 29 years). Clinical features, cortisol, and ACTH were significantly greater in the EAS group. The CD/TBA group had more nonvisualized tumors (22% vs 8%; P = .000) and smaller tumor size (4 vs 6 mm; P = .001) compared with the CD/transsphenoidal surgery group. There was female predominance in CD (2.06:1) and male predominance in EAS (2:1). Men had shorter duration of symptoms (2 years; P = .014), were younger (23 years; P = .001), had lower body mass index (25.1 kg/m²; P = .000), and had more severe disease (low bone mineral density, hypokalemia). Macroadenomas were frequent (46; 24.2%), and ACTH correlated with tumor size in CD (r = 0.226; P = .005).ConclusionOur cohort presented at an earlier age than the Western population with a distinct, but slightly lower, female predilection. Patients with CD undergoing TBA had frequent negative imaging. Men had a clinical profile suggesting aggressive disease. Microadenoma and macroadenoma were difficult to distinguish on a clinicobiochemical basis.     

Overt and Subclinical Adrenal Insufficiency in Pulmonary Tuberculosis

BackgroundTuberculosis of the adrenal glands may cause overt or subclinical adrenal insufficiency. An algorithm-based approach including assessment of paired basal cortisol and plasma adrenocorticotropic hormone (ACTH), short Synacthen, and plasma renin activity assays could be useful to diagnose all forms of adrenal insufficiency.MethodsThis cross-sectional study included consecutive, treatment-naive subjects diagnosed with pulmonary tuberculosis. Tuberculosis severity was classified by radiological criteria. Baseline parameters plus morning (8 am) serum cortisol and paired plasma ACTH were measured in all patients. Synacthen stimulation tests and plasma renin activity assays were performed as required.ResultsEighty-four treatment-naive consecutive cases of pulmonary tuberculosis were evaluated for adrenal insufficiency. Twenty-seven (32.14%) subjects had normal adrenocortical function and 8 (9.5%), 7 (8.3%), 40 (47.6%), and 2 (2.4%) subjects had stage 1, stage 2, stage 3, and stage 4 adrenal insufficiency, respectively. Serum cortisol was negatively correlated with radiological severity (P = .01) and duration of illness (P = .001). Adrenal dysfunction was present in 27.3%, 82.5%, and 80% of those with radiologically minimal, moderately advanced, and far-advanced disease, respectively. Mean cortisol was 19.74 ± 5.52, 17.42 ± 8.53, and 15.71 ± 7.14 (μg/dL) in the 3 groups, respectively (P = .042). Hyponatremia was present in 83.3% of the patients. Serum sodium was negatively correlated with severity but not with the duration of disease.ConclusionThe prevalence of overt and subclinical adrenal dysfunction in pulmonary tuberculosis was high and was correlated with disease severity and duration. An algorithmic approach may be useful to detect the same and may have important clinical implications.     

Frequency of Thyroid Hormone Replacement After Lobectomy for Differentiated Thyroid Cancer

ObjectiveTo determine the frequency of levothyroxine (LT4) supplementation after therapeutic lobectomy for low-risk differentiated thyroid cancer (DTC).MethodsThis retrospective cohort study enrolled adult patients with low-risk DTC confirmed using surgical pathology who underwent therapeutic lobectomy at a single institution from January 2016 through May 2020. The outcome measures were postoperative serum thyroid-stimulating hormone (TSH) levels and the initiation of LT4. The predictors of a postoperative TSH level of >2 mU/L and initiation of LT4 were evaluated using Cox proportional hazards models.ResultsPostoperative TSH levels were available for 115 patients (91%), of whom 97 (84%) had TSH levels >2 mU/L after thyroid lobectomy. Over a median follow-up of 2.6 years, a postoperative TSH level of >2 mU/L was associated with older age (median 52 vs 37 years; P = .01), higher preoperative TSH level (1.7 vs 0.85 mU/L; P < .001), and primary tumor size of <1 cm (38% vs 11%, P = .03). Multivariate analysis revealed that only preoperative TSH level was an independent predictor of a postoperative TSH level of >2 mU/L (hazard ratio [HR] 1.53, P = .003). Among patients with a postoperative TSH level of >2 mU/L, 66 (68%) were started on LT4 at a median of 74 days (interquartile range 41-126) after lobectomy, with 51 (77%) undergoing at least 1 subsequent dose adjustment to maintain compliance with current guidelines.ConclusionMore than 80% of the patients who underwent therapeutic lobectomy for DTC developed TSH levels that were elevated beyond the recommended range, and most of these patients were prescribed LT4 soon after the surgery.     

Sick Euthyroid Syndrome on Presentation of Patients With COVID-19: A Potential Marker for Disease Severity

ObjectivePrecise risk stratification and triage of coronavirus disease 2019 (COVID-19) patients are essential in the setting of an overwhelming pandemic burden. Clinical observation has shown a somewhat high prevalence of sick euthyroid syndrome among patients with COVID-19. This study aimed to evaluate the predictive value of free triiodothyronine (FT3) at the clinical presentation of COVID-19 for disease severity and death.MethodsThis retrospective cohort study was based on electronic medical records. The study was conducted at Sheba Medical Centre, a tertiary hospital where several acute and chronic wards have been dedicated to the treatment of patients with COVID-19. The primary outcome measure was death during hospitalization; secondary outcomes included hospitalization in intensive care, mechanical ventilation, and length of hospitalization.ResultsOf a total of 577 polymerase chain reaction-positive patients with COVID-19 hospitalized between February 27 and July 30, 2020, 90 had at least 1 measurement of thyroid-stimulating hormone, free thyroxine, and FT3 within 3 days of presentation. After applying strict exclusion criteria, 54 patients were included in the study. Patients in the lowest tertile of FT3 had significantly higher rates of mortality (40%, 5.9%, and 5.9%, P = .008), mechanical ventilation (45%, 29.4%, and 0.0%; P = .007) and intensive care unit admission (55%, 29.4%, and 5.9%, P = .006). In multivariate analyses adjusted for age, Charlson comorbidity index, creatinine, albumin, and white blood cell count. FT3 remained a significant independent predictor of death.ConclusionFT3 levels can serve as a prognostic tool for disease severity in the early presentation of COVID-19.     

COVID-19 Outcomes of Patients With Differentiated Thyroid Cancer: A Multicenter Los Angeles Cohort Study

ObjectiveCancer may be a risk factor for worse outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections. However, there is a significant variability across cancer types in the extent of disease burden and modalities of cancer treatment that may impact morbidity and mortality from coronavirus disease-19 (COVID-19). Therefore, we evaluated COVID-19 outcomes in patients with a differentiated thyroid cancer (DTC) history.MethodsThis is a retrospective cohort study of patients with a history of DTC and SARS-CoV2 infection from 2 academic Los Angeles healthcare systems. Demographic, thyroid cancer, and treatment data were analyzed for associations with COVID-19 outcomes.ResultsOf 21 patients with DTC and COVID-19, 8 (38.1%) were hospitalized and 2 (9.5%) died from COVID-19. Thyroid cancer initial disease burden and extent, treatment, or current response to therapy (eg, excellent vs incomplete) were not associated with COVID-19 severity in DTC patients. However, older age and the presence of a comorbidity other than DTC were significantly associated with COVID-19 hospitalization (P = .047 and P = .024, respectively). COVID-19–attributed hospitalization and mortality in DTC patients was lower than that previously reported in cancer patients, although similar to patients with nonthyroid malignancies in these centers.ConclusionThese data suggest that among patients with DTC, advanced age and comorbid conditions are significant contributors to the risk of hospitalization from SARS-CoV2 infection, rather than factors associated with thyroid cancer diagnosis, treatment, or disease burden. This multicenter report of clinical outcomes provides additional data to providers to inform DTC patients regarding their risk of COVID-19.     

Assessment of Insulin Infusion Requirements in COVID-19-Infected Patients With Diabetic Ketoacidosis

Background/ObjectiveCoronavirus disease 2019 (COVID-19) is thought to contribute to diabetic ketoacidosis (DKA) and worse outcomes in patients with diabetes. This study compared the cumulative insulin dose required to achieve DKA resolution in the intensive care unit among patients with type 2 diabetes and COVID-19 infection versus without COVID-19 infection.MethodsThis retrospective cohort study evaluated 100 patients—50 patients with COVID-19 in cohort 1 and 50 patients without COVID-19 in cohort 2—treated with insulin infusions for DKA at a tertiary care teaching hospital. The primary outcome was to compare the cumulative insulin dose required to achieve DKA resolution in each cohort. The secondary outcomes included time to DKA resolution, mean insulin infusion rate, and mean weight-based cumulative insulin infusion dose required to achieve DKA resolution. All endpoints were adjusted for confounders.ResultsThe mean cumulative insulin dose was 190.3 units in cohort 1 versus 116.4 units in cohort 2 (P = .0038). Patients receiving steroids had a mean time to DKA resolution of 35.9 hours in cohort 1 versus 15.6 hours in cohort 2 (P = .0014). In cohort 1 versus cohort 2, the mean insulin infusion rate was 7.1 units/hour versus 5.3 units/hour (P = .0025), whereas the mean weight-based cumulative insulin infusion dose was 2.1 units/kg versus 1.5 units/kg (P = .0437), respectively.ConclusionCOVID-19-infected patients required a significantly larger cumulative insulin dose, longer time to DKA resolution, higher insulin infusion rate, and higher weight-based insulin infusion dose to achieve DKA resolution versus non–COVID-19-infected patients with type 2 diabetes.     

Correlation of Hemoglobin A1C and Outcomes in Patients Hospitalized With COVID-19

ObjectiveDiabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19). We conducted this study to determine if there is a correlation between hemoglobin A1C (HbA1C) level and poor outcomes in hospitalized patients with diabetes and COVID-19.MethodsThis is a retrospective, single-center, observational study of patients with diabetes (defined by an HbA1C level of ≥6.5% or known medical history of diabetes) who had a confirmed case of COVID-19 and required hospitalization. All patients were admitted to our institution between March 3, 2020, and May 5, 2020. HbA1C results for each patient were divided into quartiles: 5.1% to 6.7% (32-50 mmol/mol), 6.8% to 7.5% (51-58 mmol/mol), 7.6% to 8.9% (60-74 mmol/mol), and >9% (>75 mmol/mol). The primary outcome was in-hospital mortality. Secondary outcomes included admission to an intensive care unit, invasive mechanical ventilation, acute kidney injury, acute thrombosis, and length of hospital stay.ResultsA total of 506 patients were included. The number of deaths within quartiles 1 through 4 were 30 (25%), 37 (27%), 34 (27%), and 24 (19%), respectively. There was no statistical difference in the primary or secondary outcomes among the quartiles, except that acute kidney injury was less frequent in quartile 4.ConclusionThere was no significant association between HbA1C level and adverse clinical outcomes in patients with diabetes who are hospitalized with COVID-19. HbA1C levels should not be used for risk stratification in these patients.     

Endocrine Follow-up During Post-Acute COVID-19: Practical Recommendations Based on Available Clinical Evidence

ObjectiveCOVID-19 affects multiple endocrine organ systems during the disease course. However, follow-up data post-COVID-19 is scarce; hitherto available limited data suggest that most of the biochemical endocrine dysfunctions observed during acute phase of COVID-19 tend to improve after recovery. Hence, we aim to provide a rational approach toward endocrine follow-up of patients during post-acute COVID-19.MethodsWe performed a literature review across PubMed/MEDLINE database looking into the effects of COVID-19 on endocrine system and subsequent long-term endocrine sequelae. Accordingly, we have presented a practical set of recommendations regarding endocrine follow-up post-acute COVID-19.ResultsCOVID-19 can lead to new-onset hyperglycemia/diabetes mellitus or worsening of dysglycemia in patients with preexisting diabetes mellitus. Hence, those with preexisting diabetes mellitus should ensure optimum glycemic control in the post-COVID-19 period. New-onset diabetes mellitus has been described post-acute COVID-19; hence, a selected group of patients (aged <70 years and those requiring intensive care unit admission) may be screened for the same at 3 months. Thyroid dysfunction (euthyroid sick syndrome and atypical thyroiditis) and adrenal insufficiency have been described in COVID-19; however, thyroid/adrenal functions usually normalize on follow-up; hence, widespread screening post-acute COVID-19 should not be recommended. Pituitary apoplexy and male hypogonadism have rarely been documented in COVID-19; therefore, appropriate follow-up may be undertaken as per clinical context. Hypocalcemia during COVID-19 is not uncommon; however, routine estimation of serum calcium post-COVID-19 is not warranted.ConclusionThe recommendations herein provide a rational approach that would be expected to guide physicians to better delineate and manage the endocrine sequelae during post-acute COVID-19.     

Treatment With 25-Hydroxyvitamin D3 (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter,Randomized, Placebo-Controlled,Double-Blinded Clinical Trial

ObjectiveThe goal of this randomized, double-blinded, placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D₃ (25(OH)D₃) in improving vitamin D status in vitamin D–deficient/vitamin D–insufficient patients infected with the SARS-CoV-2 (COVID-19) virus.MethodsThis is a multicenter, randomized, double-blinded, placebo-controlled clinical trial. Participants were recruited from 3 hospitals that are affiliated to [Institution Blinded for Review] and [Institution Blinded for Review].ResultsA total 106 hospitalized patients who had a circulating 25(OH)D₃ concentration of <30 ng/mL were enrolled in this study. Within 30 and 60 days, 76.4% (26 of 34) and 100% (24 of 24) of the patients who received 25(OH)D₃ had a sufficient circulating 25(OH)D₃ concentration, whereas ≤12.5% of the patients in the placebo group had a sufficient circulating 25(OH)D₃ concentration during the 2-month follow-up.We observed an overall lower trend for hospitalization, intensive care unit duration, need for ventilator assistance, and mortality in the 25(OH)D₃ group compared with that in the placebo group, but differences were not statistically significant. Treatment with oral 25(OH)D₃ was associated with a significant increase in the lymphocyte percentage and decrease in the neutrophil-to-lymphocyte ratio in the patients. The lower neutrophil-to-lymphocyte ratio was significantly associated with reduced intensive care unit admission days and mortality.ConclusionOur analysis indicated that oral 25(OH)D₃ was able to correct vitamin D deficiency/insufficiency in patients with COVID-19 that resulted in improved immune function by increasing blood lymphocyte percentage. Randomized controlled trials with a larger sample size and higher dose of 25(OH)D₃ may be needed to confirm the potential effect of 25(OH)D₃ on reducing clinical outcomes in patients with COVID-19.     

Euthyroid Sick Syndrome as a Prognostic Indicator of COVID-19 Pulmonary Involvement,Associated With Poorer Disease Prognosis and Increased Mortality

ObjectiveThe prevalence of euthyroid sick syndrome (ESS) and its association with the prognosis of COVID-19 and mortality in patients with lung involvement in COVID-19 have not yet been elucidated.MethodsClinical and laboratory data of patients with COVID-19 with or without ESS were collected retrospectively and analyzed on admission. All subjects were admitted to the Department of Internal Diseases and Clinical Pharmacology at Bieganski Hospital between December 2020 and April 2021.ResultsIn total, 310 medical records of patients with COVID-19 were analyzed retrospectively. Among 215 enrolled patients, 82 cases of ESS were diagnosed. The patients with ESS had higher pro-inflammatory factor levels, longer hospitalizations, and a higher risk of requiring high-flow nasal oxygen therapy or intubation than the patients without ESS. The Kaplan-Meier curve indicated that the patients with ESS had a lower probability of survival when computed tomography showed ≤50% parenchymal involvement compared with that in patients without ESS. However, no differences in mortality were noted in those with more than 50% parenchymal involvement. The survival curve showed that ESS was associated with a higher risk of mortality during hospitalization.ConclusionESS is closely associated with a poor prognosis, including longer hospitalizations, more frequent intubation, transfer to the intensive care unit, and a higher mortality rate in patients with COVID-19. ESS is a potential prognostic predictor of survival, regardless of lung involvement in COVID-19.     

Cardiac electrophysiology consultative experience at the epicenter of the COVID-19 pandemic in the United States

BackgroundThe COVID-19 pandemic has greatly altered the practice of cardiac electrophysiology around the world for the foreseeable future. Professional organizations have provided guidance for practitioners, but real-world examples of the consults and responsibilities cardiac electrophysiologists face during a surge of COVID-19 patients is lacking.MethodsIn this observational case series we report on 29 consecutive inpatient electrophysiology consultations at a major academic medical center in New York City, the epicenter of the pandemic in the United States, during a 2 week period from March 30-April 12, 2020, when 80% of hospital beds were occupied by COVID-19 patients, and the New York City metropolitan area accounted for 10% of COVID-19 cases worldwide.ResultsReasons for consultation included: Atrial tachyarrhythmia (31%), cardiac implantable electronic device management (28%), bradycardia (14%), QTc prolongation (10%), ventricular arrhythmia (7%), post-transcatheter aortic valve replacement conduction abnormality (3.5%), ventricular pre-excitation (3.5%), and paroxysmal supraventricular tachycardia (3.5%). Twenty-four patients (86%) were positive for COVID-19 by nasopharyngeal swab. All elective procedures were canceled, and only one urgent device implantation was performed. Thirteen patients (45%) required in-person evaluation and the remainder were managed remotely.ConclusionOur experience shows that the application of a massive alteration in workflow and personnel forced by the pandemic allowed our team to efficiently address the intersection of COVID-19 with a range of electrophysiology issues. This experience will prove useful as guidance for emerging hot spots or areas affected by future waves of the pandemic.     

Efficacy of Pulsatile Gonadotropin-Releasing Hormone Therapy in Male Patients: Comparison between Pituitary Stalk Interruption Syndrome and Congenital Hypogonadotropic Hypogonadism

ObjectivePulsatile gonadotropin-releasing hormone (GnRH), widely used to induce spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) patients, can restore the pituitary-testis axis function in men with pituitary stalk interruption syndrome (PSIS). This retrospective study aimed to compare the differences in the long-term efficacy of pulsatile GnRH therapy on PSIS and CHH.MethodsPatients with PSIS (n = 25) or CHH (n = 64) who received pulsatile GnRH therapy for ≥3 months were included in this retrospective study. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, total testosterone, and testicular size were compared.ResultsBaseline characteristics were comparable except for the lower basal testosterone, triptorelin-stimulated peak luteinizing hormone (LH), and follicle-stimulating hormone in patients with PSIS. With similar duration of treatment and a significantly higher GnRH dose (P < .001), small increments in LH (2.82 [1.4, 4.55] vs 5.89 [3.88, 8.02] IU/L; P < .001), total testosterone (0.38 [0, 1.34] vs 2.34 [1.34, 3.66] ng/mL; P < .001), and testicular volume (5.3 ± 4.5 vs 8.8 ± 4.8 mL, P < .05) were observed. However, spermatogenesis rate (52.0% vs 70.3%, P > .05), median time of sperm appearance (14 vs 11 months, P > .05), sperm concentration, and progressive motility were comparable. Basal testicular volume (hazard ratio, 1.13; 95% CI, 1.01-1.27) and peak LH levels (hazard ratio, 1.11; 95% CI, 1.0-1.23) were predictors for early sperm appearance.ConclusionsPulsatile GnRH therapy can improve gonad function and induce spermatogenesis in men with PSIS. However, its efficacy may be inferior to that in CHH.