Plasma Endocan as a Biomarker of Thrombotic Events in COVID-19 Patients.

(1) Background: Endocan is a marker of endothelial dysfunction that may be associated with thrombotic events. The aim of the study was to investigate the performance of endocan as a marker of thrombotic events in COVID-19 patients. (2) Methods: We measured endocan in plasma from 79 documented COVID-19 patients classified according to disease severity (from mild to critical). Thrombotic events were recorded. (3) Results: Endocan concentrations at admission were significantly increased according to COVID-19 severity. Levels of endocan were significantly increased in patients experiencing thrombotic events in comparison with those without (16.2 (5.5-26.7) vs. 1.81 (0.71-10.5) ng/mL, p < 0.001). However, endocan concentrations were not different between pulmonary embolism and other thrombotic events. The Receiver Operating Characteristic (ROC) analysis for the identification of thrombotic events showed an area under the ROC curve (AUC) of 0.776 with an optimal threshold at 2.83 ng/mL (93.8% sensitivity and 54.7% specificity). When combining an endocan measurement with D-dimers, the AUC increased to 0.853. When considering both biomarkers, the Kaplan-Meier survival curves showed that the combination of endocan and D-dimers better discriminated patients with thrombotic events than those without. The combination of D-dimers and endocan was independently associated with thrombotic events. (4) Conclusions: Endocan might be a useful and informative biomarker to better identify thrombotic events in COVID-19 patients.

Systematic assessment of the humoral response against SARS-CoV-2 in a French cohort of 283 patients with rheumatic diseases.

OBJECTIVES: To estimate the seroprevalence of SARS-CoV-2 infection in patients with rheumatic diseases and to specify the proportion of asymptomatic and symptomatic forms of COVID-19. METHODS: We screened for SARS-CoV-2 infection among spondyloarthritis (SpA, n=143) or rheumatoid arthritis (RA, n=140) patients in our outpatient clinic at Cochin Hospital in Paris between June and August 2020. We performed a qualitative SARS-CoV-2 serological test which detects IgG directed against the N nucleocapsid protein (anti-N) and, for some patients, against the Spike protein (anti-S). Descriptive analyses were managed. RESULTS: During June-August 2020, the SARS-CoV-2 seroprevalence rate in our population was 2.83% (8/283 patients) without significant difference between RA and SpA patients (2.14% and 3.5%, respectively). We report 11 out of 283 patients (3.8%) with a diagnosis of SARS-CoV-2 infection. Among these 11 patients, 1 patient was asymptomatic (9%) with a confirmed diagnosis of COVID-19 by anti-S serology. Of the 283 patients, 85% were under bDMARDs, mainly on rituximab (RTX) (n=44) and infliximab (IFX) (n=136). CONCLUSIONS: The seroprevalence of SARS-CoV-2 in patients with rheumatic diseases, mainly under bDMARDs treatments, was 2.83%. Among infected patients, 9% were asymptomatic. Detecting SARS-CoV-2 infections could be based on the strategy using patients' interview and anti-N serology.

Risk factors of impaired humoral response to COVID-19 vaccination in rituximab-treated patients.

OBJECTIVE: To identify which factors influence humoral response to coronavirus disease 2019 (COVID-19) vaccination in rituximab (RTX)-treated patients. METHODS: This was an observational, prospective, usual care study including consecutive patients with inflammatory rheumatic diseases in maintenance therapy with RTX. All patients received a two-dose regimen COVID-19 vaccination. Serum IgG antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins were measured at the time of the new RTX infusion. RESULTS: From the recruited patients, 16/45 (36%) produced antibodies reaching the assay cut-off value of 15 AU/ml and 29/45 (64%) had a negative serology. Within RTX-treated patients, 25 (56%) had undetectable B cells. Negative serology was associated with undetectable B cells (24/25 vs 5/20, P < 0.001). Moreover, SARS-CoV-2 spike antibodies correlated with CD19 counts (r = 0.86, P < 0.001). The effect of RTX and MTX was additive in terms of seroconversion rates (23% vs 50% in patients receiving RTX in monotherapy, P = 0.12) and SARS-CoV-2 spike antibody levels [3.80 (95% CI 3.80, 7.50) vs 75 (95% CI 3.8, 353) AU/ml in patients receiving RTX in monotherapy; P = 0.025]. Multivariate analyses including demographics, disease characteristics, gammaglobulin levels, RTX and other therapies used, CD19 counts, and the time between the last RTX infusion and vaccination identified detectable B cells as the only variable independently associated with seropositivity [odds ratio 35.2 (95% CI 3.59, 344.20)]. CONCLUSIONS: B cell depletion is the main independent contributing factor of antibody response to SARS-CoV-2 vaccination in RTX-treated patients. Monitoring CD19 may be of interest to identify the most appropriate period to perform vaccination.

Oxidative Stress and Inflammatory Biomarkers for the Prediction of Severity and ICU Admission in Unselected Patients Hospitalized with COVID-19.

OBJECTIVE: We aimed to investigate the prognostic performances of oxidative stress (OS), inflammatory and cell activation biomarkers measured at admission in COVID-19 patients. DESIGN: retrospective monocentric study. SETTING: patients with suspected SARS-CoV-2 infection (COVID-19) admitted to the hospital. PATIENTS: One hundred and sixty documented and unselected COVID-19-patients. Disease severity (from mild to critical) was scored according to NIH's classification. INTERVENTIONS: none. MEASUREMENTS AND MAIN RESULTS: We measured OS biomarkers (thiol, advanced oxidation protein products (AOPP), ischemia-modified albumin (IMA)), inflammation biomarkers (interleukin-6 (IL-6), presepsin) and cellular activation biomarkers (calprotectin) in plasma at admission. Thiol concentrations decreased while IMA, IL-6, calprotectin and PSEP increased with disease severity in COVID-19 patients and were associated with increased O2 needs and ICU admission. The best area under the receiver-operating-characteristics curve (AUC) for the prediction of ICU admission was for thiol (AUC = 0.762). A thiol concentration <154 µmol/L was predictive for ICU admission (79.7% sensitivity, 64.6% specificity, 58.8% positive predictive value, 78.9% negative predictive value). In a stepwise logistic regression, we found that being overweight, having dyspnoea, and thiol and IL-6 plasmatic concentrations were independently associated with ICU admission. In contrast, calprotectin was the best biomarker to predict mortality (AUC = 0.792), with an optimal threshold at 24.1 mg/L (94.1% sensitivity, 64.9% specificity, 97.1% positive predictive value and 98.9% negative predictive value), and survival curves indicated that high IL-6 and calprotectin concentrations were associated with a significantly increased risk of mortality. CONCLUSIONS: Thiol measurement at admission is a promising tool to predict ICU admission in COVID-19-patients, whereas IL-6 and calprotectin measurements effectively predict mortality.

Interest of screening asymptomatic older adults for SARS-CoV-2 in nursing homes

Importance: Since the beginning of the pandemic, COVID-19 affected specifically elderly people aged 70 years and over in whom the mortality rate is high. We may underestimate asymptomatic people or persons with atypical COVID-19 symptoms who may spread the disease. Objective: A large screening campaign was launched all over France in several retirement homes in order to screen asymptomatic persons for SARS-CoV-2 to isolate carriers from other residents. Methods: From April 24th to 27th 2020, mobile teams of nurses from the Hôtel-Dieu Hospital were sent to five Parisian nursing homes to conduct SARS-CoV-2 RT-PCR screening tests among all asymptomatic. Results: This cross-sectional study included 297 residents: 274 asymptomatic participants (92.3%) were tested for COVID-19, mostly women (n=249/274), median age was 90 (IQR 95% [86-94]) with females being significantly older than males (90 versus 88 years, p= 0.028). A total of 35 residents (12.8%) were tested positive for COVID-19: 29 women (11.7%) and six men (24%). The proportion of PCR-positive residents was extremely variable between retirement homes and analysis of COVID-19 positive cases dispersion in each nursing home showed there was no area cluster. Conclusion: There is a real public health interest in tracking SARS-CoV-2 positive asymptomatic elderly people in nursing homes.

Performance of 30 commercial SARS-CoV-2 serology assays in testing symptomatic COVID-19 patients.

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.

Histopathologic Features of Chilblainlike Lesions Developing in the Setting of the Coronavirus Disease 2019 (COVID-19) Pandemic.

CONTEXT.­: During the coronavirus disease 2019 pandemic, several studies have described a distinctive cutaneous manifestation with a clinical picture resembling chilblains or chilblain lupus in young patients. OBJECTIVE.­: To report the histopathologic description of a series of chilblainlike lesions appearing in the context of the severe acute respiratory syndrome coronavirus 2 epidemic. DESIGN.­: The study included 13 patients with cutaneous acral lesions resembling chilblains occurring in the setting of suspected severe acute respiratory syndrome coronavirus 2 infection with available skin biopsy. RESULTS.­: Two main histopathologic patterns were observed: a chilblainlike histopathologic pattern (10 of 13 cases; 77%) and a thrombotic vasculopathy pattern (3 of 13 cases; 23%). The chilblainlike histopathologic pattern featured a superficial and deep perivascular infiltrate of lymphocytes of varying intensity. This infiltrate was sometimes peri-eccrine and alterations of eccrine glands were present in most cases. Vacuolar alteration of the basal layer of the epidermis was found in a majority of patients. Lichenoid interface dermatitis was rarely present. The thrombotic vasculopathy pattern featured an absent or mild inflammatory infiltrate, multiple intraluminal fibrin thrombi, and ischemic epidermal necrosis. In both patterns, no true vasculitis was observed. No patient tested positive for severe acute respiratory syndrome coronavirus 2 by polymerase chain reaction, possibly because these lesions may represent late cutaneous manifestations of the disease or are associated with an early effective immune response. CONCLUSIONS.­: The relationship of chilblainlike lesions to severe acute respiratory syndrome coronavirus 2 requires further investigations. Histopathologic features mimic chilblains, chilblain lupus, and, less frequently, a thrombotic vasculopathy. Response to viral infection might trigger diverse mechanisms leading to the 2 histopathologic patterns described.

SARS-COV-2 IgG antibody response in pregnant women at delivery.

BACKGROUND: The prevalence of COVID-19 infection during pregnancy is not known. COVIPREG is a prospective French multicenter study to assess the seroprevalence at the time of delivery and the maternal and neonatal impact of COVID-19 infection during pregnancy. In order to study factors associated with poor outcomes after COVID-19 Infection during pregnancy and adapt the sample size of the study, a preliminary assessment of the prevalence of SARS-CoV-2 IgG was planned after 500 inclusions in a one perinatal center of Paris area. OBJECTIVES: To assess the prevalence of SARS-CoV-2 IgG antibody response in pregnant women at the time of delivery during the COVID-19 pandemia. STUDY DESIGN: A prospective observational study at Cochin hospital (Level III maternity). Patients admitted for delivery were offered to participate to the study. Each patient participating to the study was tested for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. RESULTS: Among the 529 patients included in the COVIPREG study between April 29 and June 26, 529 were assessed for SARS-CoV-2 IgG antibody response and 25 had a positive test, ie 4.7 % with a confidence interval at 95 % [3.0 %-6.9 %]). CONCLUSIONS: Four months after the beginning of the infection in Paris, the seroprevalence of SARS-CoV-2 IgG in pregnant women at the time of delivery is low. Studies evaluating the impact of COVID-19 infection during pregnancy should take this information in account in order to adapt the sample size.