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 Recent literature reports a strong thrombotic tendency in patients hospitalized for a Covid‐19 infection. This characteristic is quite unusual and seems specific to Covid‐19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon and report their prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe Covid‐19 infections. Methods and Results In 89 consecutive patients hospitalized for Covid‐19 infection we found a 20% prevalence of protein S deficiency and a very high ie.: 72% prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged aPTT nor with D‐dimer, fibrinogen or C‐reactive protein concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in Covid‐19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in Covid‐19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of Covid‐19 disease and should not systematically modify our strategy on prophylactic anticoagulant treatment which is already revised upwards in this pathology.

Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.

Background: Sudden olfactory loss is a major symptom of SARS-CoV-2 infection and has a negative impact on daily life quality. Almost 80% of disorders regress spontaneously. No precise characterization of the medium- and long-term olfactory symptoms has been carried out yet, apart from self-assessments. The main objective of this work was to characterize persistent smell disorders in this population. Methodology: Consecutive patients consulting to the ENT department with post-Covid19 olfactory loss were included. The clinical examination included an analog scale for the self-assessment of olfactory recovery), a nasofibroscopy, the Sniffin’ Stick Test and the short version of the Questionnaire of olfactory disorders. Results: Among the 34 patients included, based on the Sniffin’ Sticks Test, 29.4% (n=10) could be classified as normosmic, 55.9% (n=19) as hyposmic and 14.7% (n=5) as functional anosmic). Only olfactory identification impairment was significantly correlated with olfactory complaint and daily anxiety and annoyance related to lack of olfaction recovery. This identification disorder seemed to worsen over time. Conclusions: It is crucial to assess odor identification disorders in case of persistent olfactory complaints after COVID-19. It is fundamental to target this disorder, as it does not improve spontaneously and negatively impact quality of life.

Background Urinary tract infections are known to be caused by bacteria, but the potential implications of archaea have never been studied in this context. Methods In two different university hospital centres we used specific laboratory methods for the detection and culture of archaeal methanogens in 383 urine specimens prospectively collected for diagnosing urinary tract infection (UTI). Findings Methanobrevibacter smithii was detected by quantitative PCR and sequencing in 34 (9%) of the specimens collected from 34 patients. Escherichia coli, Klebsiella pneumoniae , Enterobacter sp., Enterococcus faecium and mixed cultures were detected along with M. smithii in eighteen, six, three, one and six urine samples, respectively. Interestingly, using our specific culture method for methanogens, we also isolated M. smithii in 31 (91%) of the 34 PCR positive urine samples. Genotyping the 31 isolates using multispacer sequence typing revealed three different genotypes which have been previously reported in intestinal microbiota. Antibiotic susceptibility testing found the 31 isolates to be in vitro susceptible to metronidazole (MIC: 1 mg/L) but resistant to fosfomycin, sulfamethoxazole-trimethoprim, amoxicillin-clavulanate and ofloxacin, commonly used to treat bacterial UTI. Finally, 19 (54%) of the 34 patients in whose urine samples M. smithii was detected were diagnosed with UTIs, including cystitis, pyelonephritis and prostatitis. Interpretation Our results show that M. smithii is part of the urinary microbiota of some individuals and could play a role in community-acquired UTI in association with enteric bacteria. Fund This study was supported by IHU Méditerranée Infection, Marseille, France.