Severe SARS-Cov2 pneumonia in vaccinated patients: a multicenter cohort study.

Vaccination reduces risk of infection, hospitalization, and death due to SARS-Cov2. Vaccinated patients may however experience severe SARS-Cov2 disease. The objective was to describe clinical features of vaccinated patients requiring intensive care unit (ICU) admission due to SARS-Cov2 infection and compare them to a published cohort of unvaccinated patients. We performed a multicenter cohort study of patients with severe SARS-Cov2 disease admitted to 15 ICUs in France between January and September 2021. 100 consecutive vaccinated patients (68 (68%) men, median age 64 [57-71]) were included. Immunosuppression was reported in 38 (38%) patients. Among available serologies at ICU admission, 64% exhibited an optimal antibody level. Median SOFA score at ICU admission was 4 [4-6.3] and median PaO2/FiO2 ratio was 84 [69-128] mmHg. A total of 79 (79%) and 18 (18%) patients received high flow nasal oxygen and non-invasive mechanical ventilation, respectively. Invasive mechanical ventilation (IMV) was initiated in 48 (48%) with a median duration of 11 [5-19] days. During a median ICU length-of-stay of 8 [4-20] days, 31 (31%) patients died. Age (OR per 5-years increment 1.38 CI95% [1.02-1.85], p = 0.035), and SOFA at ICU admission (OR 1.40 CI95% [1.14-1.72] per point, p = 0.002) were independently associated with mortality. When compared to a cohort of 1316 unvaccinated patients (72% men, median age 63 [53-71]), vaccinated patients exhibited less frequently diabetes (16 [16%] vs. 351 [27%], p = 0.029) but were more frequently immunosuppressed (38 [38%] vs. 109 (8.3%), p < 0.0001), had more frequently chronic kidney disease (24 [24%] vs. 89 (6.8%), p < 0.0001), chronic heart failure (16 [16%] vs. 58 [4.4%], p < 0.0001), and chronic liver disease (3 [3%] vs. 8 [0.6%], p = 0.037) compared to unvaccinated patients. Despite similar severity, vaccinated patients required less frequently IMV at ICU day 1 and during ICU stay (23 [23%] vs. 785 [59.7%], p < 0.0001, and 48 [48%] vs. 930 [70.7%], p < 0.0001, respectively). There was no difference concerning ICU mortality (31 [31%] vs. 379 [28.8%], p = 0.64). Severe SARS-Cov2 infection after vaccination occurs mainly in patients with immunosuppression, chronic kidney, heart or liver failure. Age and disease severity are independently associated with mortality.

COVID-19 outcomes in giant cell arteritis and polymyalgia rheumatica versus rheumatoid arthritis: A national, multicenter, cohort study.

OBJECTIVES: To determine whether giant cell arteritis and polymyalgia rheumatica (GCA/PMR) represent independent risk factors for worse outcomes in COVID-19. METHODS: Observational, national, French, multicenter cohort (NCT04353609) comprising patients aged ≥18 years with confirmed diagnoses of either GCA, PMR or rheumatoid arthritis (RA) having presented COVID-19; those under rituximab were excluded. Primary endpoint was COVID-19 severity in GCA/PMR patients as compared to RA. We also aimed to describe the evolution of GCA/PMR patients following COVID-19. Multinomial logistic regression models were performed, with and without adjustment on pre-specified confounding factors (i.e., age, sex, body mass index, arterial hypertension, diabetes and cardiovascular disease). Unadjusted and adjusted multinomial odds-ratio (OR/aOR) and their 95% confidence intervals (CIs) were calculated as effect size using RA as reference group. RESULTS: Between April 15, 2020, and August 20, 2021, 674 patients [45 (6.6%) GCA, 47 (7.0%) PMR, 582 (86.4%) RA; 62.8 years, 73.2% female] were included. Compared to RA patients, those with GCA/PMR were older and more frequently presented hypertension, diabetes and cardiovascular disease. Severe COVID-19 and death occurred in 24 (26.1%) and 16 (17.8%) patients with GCA/PMR, respectively. Unadjusted analyses revealed higher odds of severe COVID-19 [OR = 3.32 (95% CI 1.89-5.83; p < 0.001)] and death [OR = 3.20 (95%CI 1.67-6.13; p < 0.001)] for GCA/PMR compared to RA. After model adjustment, these odds were attenuated. CONCLUSION: Patients with GCA/PMR were more likely to have severe COVID-19 and higher mortality compared to those with RA. This worse prognosis is mostly due to well known risk factors for the general population rather than vasculitis per se.

Cardiac adipose tissue volume and IL-6 level at admission are complementary predictors of severity and short-term mortality in COVID-19 diabetic patients.

BACKGROUND: COVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission. METHODS: Eighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined. RESULTS: Of the enrolled patients (median age 66 years [IQR: 59-74]), 73% male, median body mass index (BMI) 27 kg/m2 [IQR: 24-31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2, p < 0.0001) and ICU-R (respectively OR = 3.27, p = 0.01; OR = 4.86, p = 0.002). These associations remained significant independently of age, sex, BMI as well as troponin-T level and pulmonary lesion extension in CT. We combined CATi and IL-6 levels as a multiplicative interaction score (CATi*IL-6). The cut-point for this score was ≥ 6386 with a sensitivity of 0.90 and a specificity of 0.87 (AUC = 0.88) and an OR of 59.6 for early mortality (p < 0.0001). CONCLUSIONS: Cardiac adipose tissue index and IL-6 determination at admission could help physicians to better identify diabetic patients with a potentially severe and lethal short term course irrespective of obesity. Diabetic patients with high CATi at admission, a fortiori associated with high IL-6 levels could be a relevant target population to promptly initiate anti-inflammatory therapies.

[Differences of characteristics and outcomes between cancer patients and patients with no active cancer hospitalised for a SARS-CoV-2 infection]. / Comparaison des caractéristiques et des pronostics des patients avec et sans cancer actif hospitalisés pour une infection à SARS-CoV-2.

BACKGROUND: Patients with solid cancer or haematologic malignancies have been considered to be more susceptible to SARS-CoV-2 infection and to more often develop severe complications. We aimed to compare the differences in clinical features and outcomes of COVID-19 patients with and without cancer. METHODS: This was a prospective observational cohort study of consecutive adult patients hospitalised in a COVID-19 unit at Pitié-Salpêtrière Hospital, Paris, France (NCT04320017). RESULTS: Among the 262 patients hospitalised in a medical ward during the pandemics with a confirmed COVID-19 diagnosis, 62 patients had cancer. Clinical presentation, comorbidities, and outcomes were similar between cancer and non-cancer patients. However, cancer patients were more likely to have been contaminated while being hospitalised. CONCLUSIONS: Oncologic and non-oncologic patients hospitalised for COVID-19 shared similar outcomes in terms of death, admission in intensive care, or thrombosis/bleeding. They should benefit from the same therapeutic strategy as the general population during the COVID-19 pandemic.

SARS-CoV-2 outbreak in immune-mediated inflammatory diseases: the Euro-COVIMID multicentre cross-sectional study.

BACKGROUND: The COVID-19 pandemic has raised numerous questions among patients with immune-mediated inflammatory diseases regarding potential reciprocal effects of COVID-19 and their underlying disease, and potential effects of immunomodulatory therapy on outcomes related to COVID-19. The seroprevalence of SARS-CoV-2 and factors associated with symptomatic COVID-19 in patients with immune-mediated inflammatory diseases are still unclear. The Euro-COVIMID study aimed to determine the serological and clinical prevalence of COVID-19 among patients with immune-mediated inflammatory diseases, as well as factors associated with COVID-19 occurrence and the impact of the pandemic in its management. METHODS: In this multicentre cross-sectional study, patients aged 18 years or older with a clinical diagnosis of rheumatoid arthritis, axial spondyloarthritis, systemic lupus erythematosus, Sjögren's syndrome, or giant cell arteritis were recruited from six tertiary referral centres in France, Germany, Italy, Portugal, Spain, and the UK. Demographics, comorbidities, treatments, and recent disease flares, as well as information on COVID-19 symptoms, were collected through a questionnaire completed by participants. SARS-CoV-2 serology was systematically tested. The main outcome was the serological and clinical prevalence of COVID-19. Factors associated with symptomatic COVID-19 were assessed by multivariable logistic regression, and incidence of recent disease flares, changes in treatments for underlying disease, and the reasons for treatment changes were also assessed. This study is registered with ClinicalTrials.gov, NCT04397237. FINDINGS: Between June 7 and Dec 8, 2020, 3136 patients with an immune-mediated inflammatory disease answered the questionnaire. 3028 patients (median age 58 years [IQR 46-67]; 2239 [73·9%] women and 789 [26·1%] men) with symptomatic COVID-19, serological data, or both were included in analyses. SARS-CoV-2 antibodies were detected in 166 (5·5% [95% CI 4·7-6·4]) of 3018 patients who had serology tests. Symptomatic COVID-19 occurred in 122 (4·0% [95% CI 3·4-4·8]) of 3028 patients, of whom 24 (19·7%) were admitted to hospital and four (3·3%) died. Factors associated with symptomatic COVID-19 were higher concentrations of C-reactive protein (odds ratio 1·18, 95% CI 1·05-1·33; p=0·0063), and higher numbers of recent disease flares (1·27, 1·02-1·58; p=0·030), whereas use of biological therapy was associated with reduced risk (0·51, 0·32-0·82; p=0·0057). At least one disease flare occurred in 654 (21·6%) of 3028 patients. Over the study period, 519 (20·6%) of 2514 patients had treatment changes, of which 125 (24·1%) were due to the pandemic. INTERPRETATION: This study provides key insights into the epidemiology and risk factors of COVID-19 among patients with immune-mediated inflammatory diseases. Overall, immunosuppressants do not seem to be deleterious in this scenario, and the control of inflammatory activity seems to be key when facing the pandemic. FUNDING: Pfizer, Sanofi, Amgen, Galapagos, and Lilly.

Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19.

BACKGROUND: Hydroxychloroquine (HCQ) dosage required to reach circulating levels that inhibit SARS-Cov-2 are extrapolated from pharmacokinetic data in non-COVID-19 patients. METHODS: We performed a population-pharmacokinetic analysis from 104 consecutive COVID-19 hospitalized patients (31 in intensive care units, 73 in medical wards, n=149 samples). Plasma HCQ concentration were measured using high performance liquid chromatography with fluorometric detection. Modelling used Monolix-2019R2. RESULTS: HCQ doses ranged from 200 to 800mg/day administered for 1 to 11days and median HCQ plasma concentration was 151ng/mL. Among the tested covariates, only bodyweight influenced elimination oral clearance (CL) and apparent volume of distribution (Vd). CL/F (F for unknown bioavailability) and Vd/F (relative standard-error, %) estimates were 45.9L/h (21.2) and 6690L (16.1). The derived elimination half-life (t1/2) was 102h. These parameters in COVID-19 differed from those reported in patients with lupus, where CL/F, Vd/F and t1/2 are reported to be 68L/h, 2440 L and 19.5h, respectively. Within 72h of HCQ initiation, only 16/104 (15.4%) COVID-19 patients had HCQ plasma levels above the in vitro half maximal effective concentration of HCQ against SARS-CoV-2 (240ng/mL). HCQ did not influence inflammation status (assessed by C-reactive protein) or SARS-CoV-2 viral clearance (assessed by real-time reverse transcription-PCR nasopharyngeal swabs). CONCLUSION: The interindividual variability of HCQ pharmacokinetic parameters in severe COVID-19 patients was important and differed from that previously reported in non-COVID-19 patients. Loading doses of 1600mg HCQ followed by 600mg daily doses are needed to reach concentrations relevant to SARS-CoV-2 inhibition within 72hours in≥60% (95% confidence interval: 49.5-69.0%) of COVID-19 patients.

Performance of serum apolipoprotein-A1 as a sentinel of Covid-19.

BACKGROUND: Since 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19. METHODS: We compared the daily mean serum apolipoprotein-A1 during the first 34 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (212,297 serum) and in France (20,652 serum) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (266,976 and 28,452 serum, respectively). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population. RESULTS: The mean serum apolipoprotein-A1 levels in the survey populations began decreasing in January 2020, compared to the same period in 2019. This decrease was highly correlated with the daily increase in confirmed Covid-19 cases in the following 34 weeks, both in France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2-95.1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957-0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio of apolipoprotein-A1 for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0; P = 0.04). CONCLUSION: Apolipoprotein-A1 could be a sentinel of the pandemic in existing routine surveillance of the general population. NCT01927133, CER-2020-14.

Development of a multivariate prediction model of intensive care unit transfer or death: A French prospective cohort study of hospitalized COVID-19 patients.

Prognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the management of COVID-19 patients hospitalized in a medical ward. This French single-center prospective cohort study evaluated 152 patients with positive severe acute respiratory syndrome coronavirus 2 real-time reverse transcriptase-polymerase chain reaction assay, hospitalized in the Internal Medicine and Clinical Immunology Department, at Pitié-Salpêtrière's Hospital, in Paris, France, a tertiary care university hospital. Predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death) were evaluated in multivariable logistic regression models; models' performances, including discrimination and calibration, were assessed (C-index, calibration curve, R2, Brier score). A validation was performed on an external sample of 132 patients hospitalized in a French hospital close to Paris, in Aulnay-sous-Bois, Île-de-France. The probability of ICU transfer or death was 32% (47/147) (95% CI 25-40). Older age (OR 2.61, 95% CI 0.96-7.10), poorer respiratory presentation (OR 4.04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1.76-9.25), higher CRP-level (OR 1.63 per 100mg/L increment, 95% CI 0.98-2.71) and lower lymphocytes count (OR 0.36 per 1000/mm3 increment, 95% CI 0.13-0.99) were associated with an increased risk of ICU requirement or death. A 9-point ordinal scale scoring system defined low (score 0-2), moderate (score 3-5), and high (score 6-8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14. Therefore, in this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, a simplified scoring system at admission predicted the outcome at D14.

Prevalence of hyposmia and hypogeusia in 390 COVID-19 hospitalized patients and outpatients: a cross-sectional study.

Anecdotal evidence rapidly accumulated during March 2020 from sites around the world that sudden hyposmia and hypogeusia are significant symptoms associated with the SARS-CoV-2 pandemic. Our objective was to describe the prevalence of hyposmia and hypogeusia and compare it in hospitalized and non-hospitalized COVID-19 patients to evaluate an association of these symptoms with disease severity. We performed a cross-sectional survey during 5 consecutive days in March 2020, within a tertiary referral center, associated outpatient clinic, and two primary care outpatient facilities in Paris. All SARS-CoV-2-positive patients hospitalized during the study period and able to be interviewed (n = 198), hospital outpatients seen during the previous month (n = 129), and all COVID-19-highly suspect patients in two primary health centers (n = 63) were included. Hospitalized patients were significantly more often male (64 vs 40%) and older (66 vs 43 years old in median) and had significantly more comorbidities than outpatients. Hyposmia and hypogeusia were reported by 33% of patients and occurred significantly less frequently in hospitalized patients (12% and 13%, respectively) than in the health centers' outpatients (33% and 43%, respectively) and in the hospital outpatients (65% and 60%, respectively). Hyposmia and hypogeusia appeared more frequently after other COVID-19 symptoms. Patients with hyposmia and/or hypogeusia were significantly younger and had significantly less respiratory severity criteria than patients without these symptoms. Olfactory and gustatory dysfunction occurs frequently in COVID-19, especially in young, non-severe patients. These symptoms might be a useful tool for initial diagnostic work-up in patients with suspected COVID-19.

Expert opinion on the management and follow-up of uveitis patients during SARS-CoV-2 outbreak.

INTRODUCTION: Routine medical and ophthalmic care is being drastically curtailed in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Uveitis patients require particular attention because of their theoretical risk of viral infection, in the context of therapeutic immunosuppression. AREAS COVERED: This collaborative work proposes practical management and follow-up criteria for uveitis patients in the context of the ongoing SARS-CoV-2 pandemic. EXPERT OPINION: Management should proceed as usual when access to health care possible in patients who do not belong to a group at high risk of severe SARS-CoV-2 infection, and in uncontrolled uveitis cases. In case of reduced access to eye clinics or high risk of SARS-CoV-2 infection, patients' management should be stratified based on their clinical presentation. In non-severe uveitis cases, the use of systemic steroids should be avoided, and local steroids preferred whenever possible. In uncontrolled situations where there is real risk of permanent visual loss, high-dose intravenous steroids and/or systemic immunosuppressants and/or biotherapies can be administered depending on the severity of eye disease. Immunosuppressive therapy should not be withheld, unless the patient develops SARS-CoV2 infection.