Minerals and Antioxidant Micronutrients Levels and Clinical Outcome in Older Patients Hospitalized for COVID-19 during the First Wave of the Pandemic.

Excessive inflammatory response has been implicated in severe respiratory forms of coronavirus disease 2019 (COVID-19). Trace elements such as zinc, selenium, and copper are known to modulate inflammation and immunity. This study aimed to assess the relationships between antioxidant vitamins and mineral trace elements levels as well as COVID-19 severity in older adults hospitalized. In this observational retrospective cohort study, the levels of zinc, selenium, copper, vitamin A, ß-carotene, and vitamin E were measured in 94 patients within the first 15 days of hospitalization. The outcomes were in-hospital mortality secondary to COVID-19 or severe COVID-19. A logistic regression analysis was conducted to test whether the levels of vitamins and minerals were independently associated with severity. In this cohort (average age of 78 years), severe forms (46%) were associated with lower zinc (p = 0.012) and ß-carotene (p < 0.001) concentrations, and in-hospital mortality (15%) was associated with lower zinc (p = 0.009), selenium (p = 0.014), vitamin A (p = 0.001), and ß-carotene (p = 0.002) concentrations. In regression analysis, severe forms remained independently associated with lower zinc (aOR 2.13, p = 0.018) concentrations, and death was associated with lower vitamin A (aOR = 0.165, p = 0.021) concentrations. Low plasma concentrations of zinc and vitamin A were associated with poor prognosis in older people hospitalized with COVID-19.

Prior SARS-CoV-2 infection enhances and reshapes spike protein-specific memory induced by vaccination.

The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein-specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein-specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced TH1 polarization of their SARS-CoV-2 spike protein-specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein-specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein-specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.

Vitamin D and COVID-19 Severity in Hospitalized Older Patients: Potential Benefit of Prehospital Vitamin D Supplementation.

Studies involving the associations between vitamin D supplementation taken before the onset of COVID-19 infection and the clinical outcomes are still scarce and this issue remains controversial. This study aimed to assess the relationships between vitamin D (VitD) status and supplementation and coronavirus disease 2019 (COVID-19) severity in older adults (average age of 78 years) hospitalized for COVID-19. We conducted an observational retrospective cohort study with 228 older hospitalized patients during the first wave of the COVID-19 pandemic. The outcomes were in-hospital mortality secondary to COVID-19 or critically severe COVID-19. A logistic regression analysis was conducted to test whether pre-hospital VitD supplementation was independently associated with severity. In this study, 46% of patients developed a severe form and the overall in-hospital mortality was 15%. Sixty-six (29%) patients received a VitD supplement during the 3 months preceding the infection onset. Additionally, a VitD supplement was associated with fewer severe COVID-19 forms (OR = 0.426, p = 0.0135) and intensive care unit (ICU) admissions (OR = 0.341, p = 0.0076). As expected, age > 70 years, male gender and BMI ≥ 35 kg/m2 were independent risk factors for severe forms of COVID-19. No relationship between serum 25(OH)D levels and the severity of the COVID-19 was identified. VitD supplementation taken during the 3 months preceding the infection onset may have a protective effect on the development of severe COVID-19 forms in older adults. Randomized controlled trials and large-scale cohort studies are necessary to strengthen this observation.

T cell response against SARS-CoV-2 persists after one year in patients surviving severe COVID-19.

BACKGROUND: In critically ill COVID-19 patients, the initial response to SARS-CoV-2 infection is characterized by major immune dysfunctions. The capacity of these severe patients to mount a robust and persistent SARS-CoV-2 specific T cell response despite the presence of severe immune alterations during the ICU stay is unknown. METHODS: Critically ill COVID-19 patients were sampled five times during the ICU stay and 9 and 13 months afterwards. Immune monitoring included counts of lymphocyte subpopulations, HLA-DR expression on monocytes, plasma IL-6 and IL-10 concentrations, anti-SARS-CoV-2 IgG levels and T cell proliferation in response to three SARS-CoV-2 antigens. FINDINGS: Despite the presence of major lymphopenia and decreased monocyte HLA-DR expression during the ICU stay, convalescent critically ill COVID-19 patients consistently generated adaptive and humoral immune responses against SARS-CoV-2 maintained for more than one year after hospital discharge. Patients with long hospital stays presented with stronger anti-SARS-CoV-2 specific T cell response but no difference in anti-SARS-CoV2 IgG levels. INTERPRETATION: Convalescent critically ill COVID-19 patients consistently generated a memory immune response against SARS-CoV-2 maintained for more than one year after hospital discharge. In recovered individuals, the intensity of SARS-CoV-2 specific T cell response was dependent on length of hospital stay. FUNDING: This observational study was supported by funds from the Hospices Civils de Lyon, Fondation HCL, Claude Bernard Lyon 1 University and Région Auvergne Rhône-Alpes and by partial funding by REACTing (Research and ACTion targeting emerging infectious diseases) INSERM, France and a donation from Fondation AnBer (http://fondationanber.fr/).

Baseline clinical features of COVID-19 patients, delay of hospital admission and clinical outcome: A complex relationship.

INTRODUCTION: Delay between symptom onset and access to care is essential to prevent clinical worsening for different infectious diseases. For COVID-19, this delay might be associated with the clinical prognosis, but also with the different characteristics of patients. The objective was to describe characteristics and symptoms of community-acquired (CA) COVID-19 patients at hospital admission according to the delay between symptom onset and hospital admission, and to identify determinants associated with delay of admission. METHODS: The present work was based on prospective NOSO-COR cohort data, and restricted to patients with laboratory confirmed CA SARS-CoV-2 infection admitted to Lyon hospitals between February 8 and June 30, 2020. Long delay of hospital admission was defined as ≥6 days between symptom onset and hospital admission. Determinants of the delay between symptom onset and hospital admission were identified by univariate and multiple logistic regression analysis. RESULTS: Data from 827 patients were analysed. Patients with a long delay between symptom onset and hospital admission were younger (p<0.01), had higher body mass index (p<0.01), and were more frequently admitted to intensive care unit (p<0.01). Their plasma levels of C-reactive protein were also significantly higher (p<0.01). The crude in-hospital fatality rate was lower in this group (13.3% versus 27.6%), p<0.01. Multiple analysis with correction for multiple testing showed that age ≥75 years was associated with a short delay between symptom onset and hospital admission (≤5 days) (aOR: 0.47 95% CI (0.34-0.66)) and CRP>100 mg/L at admission was associated with a long delay (aOR: 1.84 95% CI (1.32-2.55)). DISCUSSION: Delay between symptom onset and hospital admission is a major issue regarding prognosis of COVID-19 but can be related to multiple factors such as individual characteristics, organization of care and severe pathogenic processes. Age seems to play a key role in the delay of access to care and the disease prognosis.

Tobacco smoking and severity of COVID-19: Experience from a hospital-based prospective cohort study in Lyon, France.

Information gathered so far from published studies attest the existence of a complex relationship between tobacco smoking and the severity of COVID-19. We investigated the association between smoking habits and the severity of COVID-19 in patients hospitalized in university-affiliated hospitals in Lyon, France. Baseline sociodemographic, clinical and biological characteristics of adult COVID-19 hospitalized patients presenting from the community were prospectively collected and analyzed. Tobacco exposure was documented at admission. Characteristics of patients hospitalized in medical wards to those admitted or transferred to intensive care units (ICUs) were compared using Mann-Whitney and Χ2 or Fisher's exact test. A composite endpoint including admission or transfer to ICU or death was created as a proxy for severe outcome. Adjusted odds ratio (aOR) and 95% confidence interval (95% CI) were calculated to identify variables independently associated with a severe outcome. Of the 645 patients with documented information on smoking habits, 62.6% were never-smokers, 32.1% ex-smokers, and 5.3% active smokers. Past tobacco use was independently associated with an increased risk of severe outcome (aOR: 1.71; 95% CI: 1.12-2.63), whereas a nonsignificant protective trend was found for active smoking. The results suggest that past smoking is associated with enhanced risk of progressing toward severe COVID-19 disease in hospitalized patients.

Protocol for a prospective, observational, hospital-based multicentre study of nosocomial SARS-CoV-2 transmission: NOSO-COR Project.

INTRODUCTION: The newly identified SARS-CoV-2 can cause serious acute respiratory infections such as pneumonia. In France, mortality rate in the general population was approximately 10% and could reach higher levels at the hospital. In the current context of high incidence rates of SARS-CoV-2 in the community, a significant increase in the rate of nosocomial transmission is expected. The risk of nosocomial transmission could even be higher in low-income countries that have fragile healthcare systems. This protocol is intended to estimate the prevalence and incidence of suspected or confirmed cases of nosocomial SARS-CoV-2 infection, the clinical spectrum and the determinants (risk factors/protective) at participating hospitals. METHODS AND ANALYSIS: This will be an international multicentre prospective, observational, hospital-based study in adults and children. It will include volunteer patients and healthcare professionals in France and hospitals affiliated with the GABRIEL network. Demographic and clinical data will be collected using case report forms designed especially for the purpose of the project. A nasopharyngeal swab will be collected and tested for SARS-CoV-2 by reverse-transcriptase PCR. Characteristics of the study participants, the proportion of confirmed nosocomial SARS-CoV-2 infections relative to all patients with syndromes suggestive of SARS-CoV-2 infection, will be analysed. Appropriate multivariate modelling will be used to identify the determinants associated with nosocomial onset. ETHICS AND DISSEMINATION: This study was approved by the clinical research and committee of all participating countries. The findings will be submitted to peer-reviewed journal for publication and shared with national health authorities. TRIAL REGISTRATION NUMBER: NCT04290780.

Factors associated with admission to intensive care units in COVID-19 patients in Lyon-France.

INTRODUCTION: A new respiratory virus, SARS-CoV-2, has emerged and spread worldwide since late 2019. This study aims at analysing clinical presentation on admission and the determinants associated with admission in intensive care units (ICUs) in hospitalized COVID-19 patients. PATIENTS AND METHODS: In this prospective hospital-based study, socio-demographic, clinical and biological characteristics, on admission, of adult COVID-19 hospitalized patients presenting from the community for their first admission were prospectively collected and analysed. Characteristics of patients hospitalized in medical ward to those admitted in ICU were compared using Mann-Whitney and Chi-square or Fisher exact test when appropriate. Univariate logistic regression was first used to identify variables on admission that were associated with the outcome i.e. admission to an ICU versus total hospital stay in a medical ward. Forward selection was then applied beginning with sex, age and temperature in the multivariable logistic regression model. RESULTS: Of the 412 patients included, 325 were discharged and 87 died in hospital. Multivariable regression showed increasing odds of ICU hospitalization with temperature (OR, 1.56 [95% CI, 1.06-2.28] per degree Celsius increase), oxygen saturation <90% (OR, 12.45 [95% CI, 5.27-29.4]), abnormal lung auscultation on admission (OR, 3.58 [95% CI, 1.58-8.11]), elevated level of CRP (OR, 2.7 [95% CI, 1.29-5.66for CRP>100mg/L vs CRP<10mg/L). and monocytopenia (OR, 3.28 [95% CI, 1.4-7.68]) were also associated with increasing odds of ICU hospitalization. Older patients were less likely to be hospitalized in ICU (OR, 0.17 [95%CI, 0.05-0.51]. CONCLUSIONS: Age and delay between onset of symptoms and hospital admission were associated with the risk of hospitalisation in ICU. Age being a fixed variable, interventions that shorten this delay would improve the prognosis of Covid-19 patients.