Androgen receptor polyQ alleles and COVID-19 severity in men: A replication study.

BACKGROUND: Ample evidence indicates a sex-related difference in severity of COVID-19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID-19 severity. OBJECTIVE: To test the association between the androgen receptor polyQ polymorphism and COVID-19 severity in a large cohort of COVID-19 male patients. MATERIALS AND METHODS: This study included 1136 male patients infected with SARS-CoV-2 as confirmed by positive PCR. Patients were retrospectively and prospectively enrolled from March to November 2020. Patients were classified according to their severity into three categories: oligosymptomatic, hospitalized and severe patients requiring ventilatory support. The number of CAG repeats (polyQ polymorphism) at the androgen receptor was obtained by PCR and patients were classified as either short (<23 repeats) or long (≥23 repeats) allele carriers. The association between polyQ alleles (short or long) and COVID-19 severity was assessed by Chi-squared (Chi2 ) and logistic regression analysis. RESULTS: The mean number of polyQ CAG repeats was 22 (±3). Patients were classified as oligosymptomatic (15.5%), hospitalized (63.2%), and severe patients (21.3%) requiring substantial respiratory support. PolyQ alleles distribution did not show significant differences between severity classes in our cohort (Chi2 test p > 0.05). Similar results were observed after adjusting by known risk factors such as age, comorbidities, and ethnicity (multivariate logistic regression analysis). DISCUSSION: Androgen sensitivity may be a critical factor in COVID-19 disease severity. However, we did not find an association between the polyQ polymorphism and the COVID-19 severity. Additional studies are needed to clarify the mechanism underlying the association between androgens and COVID-19 outcome. CONCLUSIONS: The results obtained in our study do not support the role of this polymorphism as biomarker of COVID-19 severity.

Feasibility of telemedicine in the management strategy of patients with lymphoma amid the COVID-19 pandemic in Spain, a prospective study.

BACKGROUND: In March 14, 2020, the state of alarm and was declared in Spain due to the spread of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Beyond this date, the coronavirus disease 2019 (COVID-19) in the country changed the practice of oncologic care. OBJECTIVE: Since recurrent hospital visits were potential risk factors for contagion, the aims of this prospective observational study was to analyze the consequences of COVID-19 pandemic in the health care of patients with lymphoma. METHODS: All data were obtained from the electronic medical record (EMR). Variables such as age, sex, matter of the visit, use of patient's portal, changes in management, impact in clinical trials and suffering from COVID-19 contagion were recorded. RESULTS: 290 patients were attended in the lymphoma clinic accomplishing 437 appointments. The median age was 66 years (range 18-94) and 157 (54.13%) were male. Of them, 214 patients (73.79%) had only 1 visit to the clinic. Only 23 patients (7.93%) didn't have access to patient's portal. Amid the COVID-19 pandemic, 78 patients (26.89%) remained in active treatment, 35 patients (12.06%) suffered from delayed in their treatments and 6 patients (2.06%) suffered from treatment discontinuation. During the follow-up, only 8 patients (2.75%) suffered from COVID-19 (7 cases with confirmed PCR test and 1 case with clinical suspicion). Despite the implementation of telemedicine strategies to avoid visit to hospital, 66 patients (22.75%) had in-person visits to the lymphoma clinic. Patients who attended in-person consultation were younger than those who preferred telemedicine consultation (62 vs 66 years) and had less use of patient's portal (7.58% vs 9%), although these differences didn't reach statistical significance. Patients who atttended in-person visits used to have only 1 visit to hospital (43.93% vs 82.58%, P<.0001). Regarding the matter of in-person consultation, more patients were on active treatment in comparison with those using telemedicine resources (56.06% vs 18.30%, P<.0001). Patients with preference for telemedicine strategies had more surveillance visits (65.62% vs 36.36%, P<.0001). With regards of treatment modifications, more treatment delays (12.94% vs 9.09%) and more definite treatment discontinuations (2.67% vs 0%) were seen in patients using telemedicine resources when compared to patients attending in-person visits, although these differences didn't reach statistical significance. Regarding the type of therapy, patients attending in-person visits were more likely to receive an intravenous treatment rather than those on telemedicine (62.16% vs 40.47%, P<.0001). CONCLUSIONS: Telemedicine such as patient's portal are feasible strategies in the management of patients with lymphoma during the COVID-19 pandemic, with a reduction of in-person visits to hospital and a very low contagion rate.

The relationship between 25(OH) vitamin D levels and COVID-19 onset and disease course in Spanish patients.

OBJECTIVE: Currently, there are no definitive data on the relationship between low levels of vitamin D in the blood and a more severe disease course, in terms of the need for hospital admission, intensive care unit (ICU) stay, and mortality, in patients with coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to study the association between levels of circulating 25-hydroxyvitamin D (25(OH)D) and adverse clinical outcomes linked to SARS-CoV-2 infection. We further aimed to observe the incidence of low, below-average, and normal levels of 25(OH)D in patients hospitalized for COVID-19 between March 12, 2020, and May 20, 2020, and assess whether these values differed between these patients and a normal population. Finally, we determined whether the need for transfer to the intensive care unit (ICU) and the mortality rate were related to low levels of 25(OH)D. STUDY DESIGN: Retrospective observational study. SETTING: Quironsalud Hospitals in Madrid, Spain. PARTICIPANTS: We analyzed 1549 patients (mean age, 70 years; range, 21-104 years); 835 were male (53.9 %; mean age, 73.02 years), and 714 were female (46.1 %; mean age, 68.05 years). Subsequently, infected patients admitted to the ICU (n = 112) and those with a fatal outcome (n = 324) were analyzed. PROCEDURES: Serum concentrations of 25(OH)D were measured by electrochemiluminescence. RESULTS: More hospitalized patients (66 %, n = 1017) had low baseline levels of 25(OH)D (<20 ng/mL) than normal individuals (45 %) (p < 0.001). An analysis by age group revealed that COVID-19 patients between the ages of 20 and 80 years old had significantly lower vitamin D levels than those of the normal population (p < 0.001). Patients admitted to the ICU tended to have lower levels of 25(OH)D than other inpatients (p < 0.001); if we stratified patients by 25(OH)D levels, we observed that the rate of ICU admission was higher among patients with vitamin D deficiency (p < 0.001), indicating that higher vitamin D levels are associated with a lower risk of ICU admission due to COVID-19. ICU admission was related to sex (higher rates in men, p < 0.001) and age (p < 0.001). When using a logistic regression model, we found that vitamin D levels continued to show a statistically significant relationship with ICU admission rates, even when adjusting for sex and age. Therefore, the relationship found between vitamin D levels and the risk of ICU admission was independent of patient age and sex in both groups. Deceased patients (n = 324 tended to have lower levels of 25 (OH)D that normal population of the same age (p < 0.001). CONCLUSION: Vitamin D deficiency in patients with COVID-19 is correlated with an increased risk of hospital admission and the need for critical care. We found no clear relationship between vitamin D levels and mortality.

IL-6-based mortality prediction model for COVID-19: Validation and update in multicenter and second wave cohorts.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly variable condition. Validated tools to assist in the early detection of patients at high risk of mortality can help guide medical decisions. OBJECTIVE: We sought to validate externally, as well as in patients from the second pandemic wave in Europe, our previously developed mortality prediction model for hospitalized COVID-19 patients. METHODS: Three validation cohorts were generated: 2 external with 185 and 730 patients from the first wave and 1 internal with 119 patients from the second wave. The probability of death was calculated for all subjects using our prediction model, which includes peripheral blood oxygen saturation/fraction of inspired oxygen ratio, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, IL-6, and age. Discrimination and calibration were evaluated in the validation cohorts. The prediction model was updated by reestimating individual risk factor effects in the overall cohort (N = 1477). RESULTS: The mortality prediction model showed good performance in the external validation cohorts 1 and 2, and in the second wave validation cohort 3 (area under the receiver-operating characteristic curve, 0.94, 0.86, and 0.86, respectively), with excellent calibration (calibration slope, 0.86, 0.94, and 0.79; intercept, 0.05, 0.03, and 0.10, respectively). The updated model accurately predicted mortality in the overall cohort (area under the receiver-operating characteristic curve, 0.91), which included patients from both the first and second COVID-19 waves. The updated model was also useful to predict fatal outcome in patients without respiratory distress at the time of evaluation. CONCLUSIONS: This is the first COVID-19 mortality prediction model validated in patients from the first and second pandemic waves. The COR+12 online calculator is freely available to facilitate its implementation (https://utrero-rico.shinyapps.io/COR12_Score/).