Background With the lack of effective therapy, chemoprevention, and vaccination against SARS-CoV-2, focusing on the immediate repurposing of existing drugs gives hope of curbing the COVID-19 pandemic. A recent unbiased genomics-guided tracing of the SARS-CoV-2 targets in human cells identified vitamin D among the three top-scoring molecules manifesting potential infection mitigation patterns. Growing pre-clinical and epidemiological observational data support this assumption. We hypothesized that vitamin D supplementation may improve the prognosis of COVID-19. The aim of this trial is to compare the effect of a single oral high dose of cholecalciferol versus a single oral standard dose on all-cause 14-day mortality rate in COVID-19 older adults at higher risk of worsening. Methods The COVIT-TRIAL study is an open-label, multicenter, randomized controlled superiority trial. Patients aged ≥ 65 years with COVID-19 (diagnosed within the preceding 3 days with RT-PCR and/or chest CT scan) and at least one worsening risk factor at the time of inclusion (i.e., age ≥ 75 years, or SpO2 ≤ 94% in room air, or PaO2/FiO2 ≤ 300 mmHg), having no contraindications to vitamin D supplementation, and having received no vitamin D supplementation > 800 IU/day during the preceding month are recruited. Participants are randomized either to high-dose cholecalciferol (two 200,000 IU drinking vials at once on the day of inclusion) or to standard-dose cholecalciferol (one 50,000 IU drinking vial on the day of inclusion). Two hundred sixty participants are recruited and followed up for 28 days. The primary outcome measure is all-cause mortality within 14 days of inclusion. Secondary outcomes are the score changes on the World Health Organization Ordinal Scale for Clinical Improvement (OSCI) scale for COVID-19, and the between-group comparison of safety. These outcomes are assessed at baseline, day 14, and day 28, together with the serum concentrations of 25(OH)D, creatinine, calcium, and albumin at baseline and day 7. Discussion COVIT-TRIAL is to our knowledge the first randomized controlled trial testing the effect of vitamin D supplementation on the prognosis of COVID-19 in high-risk older patients. High-dose vitamin D supplementation may be an effective, well-tolerated, and easily and immediately accessible treatment for COVID-19, the incidence of which increases dramatically and for which there are currently no scientifically validated treatments. Trial registration ClinicalTrials.govNCT04344041. Registered on 14 April 2020 Trial status Recruiting. Recruitment is expected to be completed in April 2021.

Background Aging is one of the most important prognostic factors increasing the risk of clinical severity and mortality of COVID-19 infection. However, among patients over 75 years, little is known about post-acute functional decline. Objective The aim of this study was to identify factors associated with functional decline 3 months after COVID-19 onset, to identify long term COVID-19 symptoms and transitions between frailty statesafter COVID-19 onset in older hospitalized patients. Methods This prospective observational study included COVID-19 patients consecutively hospitalized from March to December 2020 in Acute Geriatric Ward in Nantes University Hospital. Functional decline, frailty status and long term symptoms were assessed at 3 month follow up. Functional status was assessed using the Activities of Daily Living simplified scale (ADL). Frailty status was evaluated using Clinical Frailty Scale (CFS). We performed multivariable analyses to identify factors associated with functional decline. Results Among the 318 patients hospitalized for COVID-19 infection, 198 were alive 3 months after discharge. At 3 months, functional decline occurred in 69 (36%) patients. In multivariable analysis, a significant association was found between functional decline and stroke (OR = 4,57, p = 0,003), history of depressive disorder (OR = 3,05, p = 0,016), complications (OR = 2,24, p = 0,039), length of stay (OR = 1,05, p = 0,025) and age (OR = 1,08, p = 0,028). At 3 months, 75 patients described long-term symptoms (49.0%). Of those with frailty (CFS scores ≥5) at 3-months follow-up, 30% were not frail at baseline. Increasing frailty defined by a worse CFS state between baseline and 3 months occurred in 41 patients (26.8%). Conclusions This study provides evidence that both the severity of the COVID-19 infection and preexisting medical conditions correlates with a functional decline at distance of the infection. This encourages practitioners to establish discharge personalized care plan based on a multidimensional geriatric assessment and in parallel on clinical severity evaluation.

Objectives Among patients over 75 years, little is known about functional decline due to COVID-19. The aim of this study was to explore this functional decline, compare to other infectious pneumonia. Design and Setting This case-control study included all COVID-19 patients hospitalized from March to December 2020 in Acute Geriatric Ward in Nantes University Hospital matched 1/1 with patients with pneumonia hospitalized in geriatric department between March 2017 and March 2019 (controls) on sex, age. Functional decline was assessed at 3 month follow up as it is routinely done after hospitalization in geriatric ward. We performed multivariable analyses to compare clinical outcomes between patients with COVID-19 vs controls. Results 132 pairs were matched on age (mean: 87 y-o), and sex (61% of women). In multivariable logistic regression analysis, there were no statistical significant association between COVID-19 infection and functional decline (OR=0.89 p=0.72). A statistical significant association was found between functional decline and Charlson comorbidity index (OR=1.17, p=0.039); prior fall (OR=2.08, p=0.012); malnutrition (OR=1.97, p=0.018); length of hospital stay (OR=1.05, p=0.002) and preadmission ADL(OR=1.25, p=0.049). Conclusion COVID-19 does not seem to be responsible for a more frequent or severe functional decline than other infectious pneumonia in older and comorbid population after 3 month follow up. In this population, pneumonia is associated with functional decline in almost 1 in 2 cases. The individual preadmission frailty seems to be a more important predictor of functional decline, encouraging multidimensional care management for this population. Electronic Supplementary Material Supplementary material is available in the online version of this article at 10.1007/s12603-022-1845-1.