Who Were Hospitalized Deceased Patients from COVID-19 During the First Year of Pandemic? Retrospective Analysis of 1104 Deceased Patients in South of France.

INTRODUCTION: Following the first year of the COVID-19 pandemic, a complete analysis of the characteristics of the deceased hospitalized patients was performed, to identify factors related to premature mortality and to compare patient profiles according to the epidemic periods. METHODS: Retrospective analysis of 1104 deceased patients in two University Hospitals in South-eastern France, between March 1, 2020 and March 12, 2021 from Hospital's electronic medical records was performed. RESULTS: Mean age was 80 years (± 11.1) and 10% of the deceased were younger than 65 years with specific comorbidities, e.g., genetic conditions, metastatic cancer, or massive obesity. Among the three clusters identified, two clusters (75% of deceased patients) include very elderly patients with numerous comorbidities, and differ by their proportion of dependent institutionalized patients. The third cluster is made up of younger patients with fewer but severe comorbidities. Deceased patients' profiles varied according to the epidemic periods: during the first period (March-June 2020), more patients were institutionalized. The second period (September-December2020) coincided with a higher mortality rate. CONCLUSIONS: This study confirmed that most patients hospitalized and dying from COVID-19 were frail, i.e., elderly and/or highly comorbid and that the small proportion of young patients had severe comorbidities.

The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies.

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-ß are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

[Influence of the work environment on burn-out and depression in nurses]. / Influence de l'environnement de travail sur le burn-out et la dépression des infirmiers.

Burn out is defined as a state of psychological exhaustion in the face of an unfavourable work environment. In the health sector, this includes, among other things, an excessive care burden, the lack of autonomy or control over work, the vicious circle of absenteeism, the lack of support, moral and sexual harassment, discrimination or the Covid-19 health crisis. Burn-out also increases the risk of depression among care workers.

Life-years lost by COVID-19 patients in public hospitals of Marseille (APHM-South-Eastern France): a limited death toll: a retrospective analysis.

OBJECTIVE: Between 1 March and 15 June, France experienced the first wave of the COVID-19 pandemic, during which 29 549 deaths occurred among COVID-19 patients, 17 250 of whom died in hospital. Our hypothesis is that crude mortality rates are not sufficient to assess the impact of the epidemic on public health. The objective of this paper is to estimate the potential years of life lost (YLL) of patients who died from COVID-19. METHOD: We realised a retrospective analysis of the exhaustive sample of COVID-19 PCR-positive patients who died in public hospitals of Marseille during this first wave. Data on demographic characteristics, comorbidities and care pathways were collected from medical records. The Charlson Comorbidity Index (CCI) was used to assess what would have been the probability of dying within 1 year of these patients in the absence of COVID-19 and to estimate total YLL. RESULTS: Among the 1631 patients who were hospitalised for COVID-19, 178 patients died, at an average age of 80 years. According to CCI, 88.8% of the deceased patients had an 85% probability of dying within 1 year before COVID-19. Among the 11.2% who had a lower CCI probability, 18 out of 20 had at least one additional comorbidity known to be a major risk factor of mortality in COVID-19 disease. Cumulative total number of YLL was estimated to be 541 in this deceased population, that is, an average of 3 YLL. CONCLUSION: Although our results should be interpreted with caution, this analysis confirms that mortality due to COVID-19 translates into a limited number of YLL due to both old age and preexisting comorbidities in the most vulnerable patients. This fact should be better considered in public health management of the pandemic both for risk communication and design of the most appropriate protective measures.

Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients.

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-ß. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-ß do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.

Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis.

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.

High-flow oxygen therapy in elderly patients infected with SARS-CoV2 with a contraindication for transfer to an intensive care unit: A preliminary report.

OBJECTIVES: In a conventional hospital ward, we used high-flow nasal oxygen (HFNO) to treat elderly COVID-19 patients noneligible for intensive care unit transfer. METHODS: This study was conducted in the Institut Hospitalo-Universitaire Méditerranée Infection, Assistance Publique-Hôpitaux de Marseille (AP-HM), France. We used high-flow nasal oxygen (HFNO) in our conventional infectious disease ward from 15 September 2020 for elderly patients noneligible for intensive care unit transfer. RESULTS: Of the 44 patients (median age 83 years (57-94), mean: 80.25), 61.4% (27/44) were men. The median Charlson score was 7 (1-15). The median of the NEWS-2 score upon admission was 8 (3-11) and was 10 at the time of initiation of HFNO. The median PaO2/FiO2 ratio was 103 (71-151) prior to HNFO initiation. Among the 44 patients, 16 patients (36.4%) had been weaned from HFNO, and 28 patients had died (63.6%). CONCLUSIONS: In this preliminary report, we observed that HFNO saved the lives of one-third of elderly COVID-19 patients who would have systematically died.

Teleradiology as a relevant indicator of the impact of COVID-19 pandemic management on emergency room activities: a nationwide worrisome survey.

OBJECTIVES: To evaluate the impact of COVID-19's lockdown on radiological examinations in emergency services. METHODS: Retrospective, multicentre analysis of radiological examinations requested, via our teleradiology network, from 2017 to 2020 during two timeframes (calendar weeks 5-8 and then 12-15). We included CT scans or MRIs performed for strokes, multiple traumas (Body-CT), cranial traumas (CTr) and acute non-traumatic abdominal pain (ANTAP). We evaluated the number and percentages of examinations performed, of those with a pathological conclusion, and of examinations involving the chest. RESULTS: Our study included 25 centres in 2017, 29 in 2018, 43 in 2019 and 59 in 2020. From 2017 to 2019, the percentages of examinations were constant, which was also true for chest CTs. Each centre's number of examinations, gender distribution and patient ages were unchanged. In 2020, examinations significantly decreased: suspected strokes decreased by 36% (1052 vs 675, p < 0.001), Body-CT by 62% (349 vs 134, p < 0.001), CTr by 52% (1853 vs 895, p < 0.001) and for ANTAP, appendicitis decreased by 38% (45 vs 90, not statistically significant (NS)) sigmoiditis by 44% (98 vs 55, NS), and renal colic by 23% (376 vs 288, NS). The number of examinations per centre decreased by 13% (185.5 vs 162.5, p < 0.001), whereas the number of examinations of the "chest" region increased by 170% (1205 vs 3766, p < 0.001). CONCLUSION: Teleradiology enabled us to monitor the impact of the COVID-19 pandemic management on emergency activities, showing a global decrease in the population's use of care.

Pattern of SARS-CoV-2 infection among dependant elderly residents living in long-term care facilities in Marseille, France, March-June 2020.

OBJECTIVES: This study aimed to report the results of SARS-CoV-2 PCR-based screening campaigns conducted on dependent elderly residents (compared with staff members) in long-term care facilities (LTCFs) in Marseille, France, and the follow-up of positive cases. METHODS: Data from 1691 elderly residents and 1000 members of staff were retrospectively collected through interviewing the medical teams in 24 LTCFs and using the hospitals' electronic health recording systems. RESULTS: Elderly residents were predominantly female (64.8%) with a mean age of 83.0 years. SARS-CoV-2 detection among residents (226, 13.4%) was significantly higher than among staff members (87, 8.7%) (P < 0.001). Of the 226 infected residents, 37 (16.4%) were detected on a case-by-case basis due to their COVID-19 symptoms and 189 (83.6%) were detected through mass screening. Most (77.0%) had possible COVID-19 symptoms, including respiratory symptoms and signs (44.5%) and fever (46.5%); 23.0% were asymptomatic. A total of 116 (51.4%) patients received a course of oral hydroxychloroquine and azithromycin (HCQ-AZM) for ≥ 3 days; 47 (20.8%) died. Through multivariate analysis, the death rate was positively associated with being male (30.7% vs. 14.0%, OR = 3.95, P = 0.002), aged > 85 years (26.1% vs. 15.6%, OR = 2.43, P = 0.041) and receiving oxygen therapy (39.0% vs. 12.9%, OR = 5.16, P < 0.001) and negatively associated with being diagnosed through mass screening (16.9% vs. 40.5%, OR = 0.20, P= 0.001) and receiving HCQ-AZM treatment ≥ 3 days (15.5% vs. 26.4%, OR = 0.37, P = 0.02). CONCLUSION: The high proportion of asymptomatic COVID-19 patients and independent factors for mortality suggest that early diagnosis and treatment of COVID-19 patients in LTCFs may be effective in saving lives.

Baseline chest X-ray in coronavirus disease 19 (COVID-19) patients: association with clinical and laboratory data.

PURPOSE: To assess the reliability of CXR and to describe CXR findings and clinical and laboratory characteristics associated with positive and negative CXR. METHODS: Retrospective two-center study on consecutive patients admitted to the emergency department of two north-western Italian hospitals in March 2020 with clinical suspicion of COVID-19 confirmed by RT-PCR and who underwent CXR within 24 h of the swab execution. 260 patients (61% male, 62.8 ± 15.8 year) were enrolled. CXRs were rated as positive (CXR+) or negative (CXR-), and features reported included presence and distribution of airspace opacities, pleural effusion and reduction in lung volumes. Clinical and laboratory data were collected. Statistical analysis was performed with nonparametric tests, binary logistic regression (BLR) and ROC curve analysis. RESULTS: Sensitivity of CXR was 61.1% (95%CI 55-67%) with a typical presence of bilateral (62.3%) airspace opacification, more often with a lower zone (88.7%) and peripheral (43.4%) distribution. At univariate analysis, several factors were found to differ significantly between CXR+ and CXR-. The BLR confirmed as significant predictors only lactate dehydrogenase (LDH), C-reactive protein (CRP) and interval between the onset of symptoms and the execution of CXR. The ROC curve procedure determined that CRX+ was associated with LDH > 500 UI/L (AUC = 0.878), CRP > 30 mg/L (AUC = 0.830) and interval between the onset of symptoms and the execution of CXR > 4 days (AUC = 0.75). The presence of two out of three of the above-mentioned predictors resulted in CXR+ in 92.5% of cases, whereas their absence in 7.4%. CONCLUSION: CXR has a low sensitivity. LDH, CRP and interval between the onset of symptoms and the execution of CXR are major predictors for a positive CXR.