Spike-specific humoral and cellular immune responses after COVID-19 mRNA vaccination in patients with cirrhosis: A prospective single center study.

BACKGROUND AND AIMS: COVID-19 mRNA vaccines were approved to prevent severe forms of the disease, but their immunogenicity and safety in cirrhosis is poorly known. METHOD: In this prospective single-center study enrolling patients with cirrhosis undergoing COVID-19 vaccination (BNT162b2 and mRNA-1273), we assessed humoral and cellular responses vs healthy controls, the incidence of breakthrough infections and adverse events (AEs). Antibodies against spike- and nucleocapsid-protein (anti-S and anti-N) and Spike-specific T-cells responses were quantified at baseline, 21 days after the first and second doses and during follow-up. RESULTS: 182 cirrhotics (85% SARS-CoV-2-naïve) and 38 controls were enrolled. After 2 doses of vaccine, anti-S titres were significantly lower in cirrhotics vs controls [1,751 (0.4-25,000) U/mL vs 4,523 (259-25,000) U/mL, p=0.012] and in SARS-CoV-2-naïve vs previously infected cirrhotics [999 (0.4-17,329) U/mL vs 7,500 (12.5-25,000) U/mL, (p<0.001)]. T-cell responses in cirrhotics were similar to controls, although with different kinetics. In SARS-CoV-2-naïve cirrhotics, HCC, Child-Pugh B/C and BNT162b2 were independent predictors of low response. Neither unexpected nor severe AEs emerged. During follow-up, 2% turned SARS-CoV-2 positive, all asymptomatic. CONCLUSION: Humoral response to COVID-19 vaccines appeared suboptimal in patients with cirrhosis, particularly in SARS-CoV-2-naïve decompensated cirrhotics, although cellular response appeared preserved, and low breakthrough infections rate was registered.

Relationship between immune response to SARS-CoV2 vaccines and development of breakthrough infection in solid organ transplant recipients: the CONTRAST cohort.

BACKGROUND: SARS-CoV-2 vaccination in solid organ transplant (SOT) is associated with poorer antibody response (AbR) compared to non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) should yet be assessed. METHODS: Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV2 vaccination during 1-year period from February 2021, and followed-up to April 30th 2022. Patients were tested for AbR at multiple timepoints. Primary endpoint was BI (laboratory confirmed SARS-CoV2 infection ≥14 days after 2nd dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization and BI states were obtained for each type of graft and vaccination sequence with multistate survival analysis, then multivariable logistic regression was performed to analyse the risk of BI in AbR levels. RESULTS: 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received three vaccine doses, the first two consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively; while at the third dose mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed lowest probability of immunization (0.418) and highest of BI (0.323), all-mRNA-1273 vaccine-sequence showed higher probability of immunization (0.732) and lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age and shorter time from transplant. CONCLUSIONS: SOT patients with non-high-level AbR, shorter time from transplantation, and heart recipients are at highest risk of BI.

Viscoelastic Coagulation Monitor as a Novel Device to Assess Coagulation at the Bedside. A Single-Center Experience During the COVID-19 Pandemic.

Viscoelastic coagulation monitor (VCM) is a portable device developed to evaluate the viscoelastic properties of whole blood activated by contact with glass. In this study, VCM was employed to analyze the viscoelastic profiles of 36 COVID-19 intensive care patients. Full anticoagulant dose heparin (unfractionated [UFH]; low molecular weight [LMWH]) was administrated to all patients. The association between VCM and laboratory parameters was retrospectively analyzed. The administration of UFH-influenced VCM parameters prolonging clotting time (CT) and clot formation time (CFT) and reducing angle (alpha) and amplitudes of the VCM tracings (A10, A20, and maximum clot firmness [MCF]) compared with LMWH therapy. A tendency toward hypercoagulation was observed by short CT and CFT in patients receiving LMWH. Clotting time was correlated with UFH dose (Spearman's rho = 0.48, p ≤ 0.001), and no correlation was found between CT and LMWH. All VCM tracings failed to show lysis at 30 and 45 minutes, indicating the absence of fibrinolysis. A10, A20, and MCF exhibited very-good to good diagnostic accuracy for detecting platelet count and fibrinogen above the upper reference limit of the laboratory. In conclusion, VCM provided reliable results in COVID-19 patients and was easy to perform with minimal training at the bedside.

Chest X-ray findings in a large cohort of 1117 patients with SARS-CoV-2 infection: a multicenter study during COVID-19 outbreak in Italy.

To describe radiographic key patterns on Chest X-ray (CXR) in patients with SARS-CoV-2 infection, assessing the prevalence of radiographic signs of interstitial pneumonia. To evaluate pattern variation between a baseline and a follow-up CXR. 1117 patients tested positive for SARS-CoV-2 infection were retrospectively enrolled from four centers in Lombardy region. All patients underwent a CXR at presentation. Follow-up CXR was performed when clinically indicated. Two radiologists in each center reviewed images and classified them as suggestive or not for interstitial pneumonia, recording the presence of ground-glass opacity (GGO), reticular pattern or consolidation and their distribution. Pearson's χ2 test for categorical variables and McNemar test (χ2 for paired data) were performed. Patients mean age 63.3 years, 767 were males (65.5%). The main result is the large proportion of positive CXR in COVID-19 patients. Baseline CXR was positive in 940 patients (80.3%), with significant differences in age and sex distribution between patients with positive and negative CXR. 382 patients underwent a follow-up CXR. The most frequent pattern on baseline CXR was the GGO (66.1%), on follow-up was consolidation (53.4%). The most common distributions were peripheral and middle-lower lung zone. We described key-patterns and their distribution on CXR in a large cohort of COVID-19 patients: GGO was the most frequent finding on baseline CXR, while we found an increase in the proportion of lung consolidation on follow-up CXR. CXR proved to be a reliable tool in our cohort obtaining positive results in 80.3% of the baseline cases.

Efficacy of corticosteroid treatment for hospitalized patients with severe COVID-19: a multicentre study.

OBJECTIVE: To assess the efficacy of corticosteroids in patients with coronavirus disease 2019 (COVID-19). METHODS: A multicentre observational study was performed from 22 February through 30 June 2020. We included consecutive adult patients with severe COVID-19, defined as respiratory rate ≥30 breath per minute, oxygen saturation ≤93% on ambient air or arterial partial pressure of oxygen to fraction of inspired oxygen ≤300 mm Hg. We excluded patients being treated with other immunomodulant drugs, receiving low-dose corticosteroids and receiving corticosteroids 72 hours after admission. The primary endpoint was 30-day mortality from hospital admission. The main exposure variable was corticosteroid therapy at a dose of ≥0.5 mg/kg of prednisone equivalents. It was introduced as binomial covariate in a logistic regression model for the primary endpoint and inverse probability of treatment weighting using the propensity score. RESULTS: Of 1717 patients with COVID-19 evaluated, 513 were included in the study, and of these, 170 (33%) were treated with corticosteroids. During hospitalization, 166 patients (34%) met the criteria of the primary outcome (60/170, 35% in the corticosteroid group and 106/343, 31% in the noncorticosteroid group). At multivariable analysis corticosteroid treatment was not associated with lower 30-day mortality rate (adjusted odds ratio, 0.59; 95% confidence interval (CI), 0.20-1.74; p 0.33). After inverse probability of treatment weighting, corticosteroids were not associated with lower 30-day mortality (average treatment effect, 0.05; 95% CI, -0.02 to 0.09; p 0.12). However, subgroup analysis revealed that in patients with PO2/FiO2 < 200 mm Hg at admission (135 patients, 52 (38%) treated with corticosteroids), corticosteroid treatment was associated with a lower risk of 30-day mortality (23/52, 44% vs. 45/83, 54%; adjusted odds ratio, 0.20; 95% CI, 0.04-0.90; p 0.036). CONCLUSIONS: The effect of corticosteroid treatment on mortality might be limited to critically ill COVID-19 patients.

Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection: a multicentre cohort study (PREDI-CO study).

OBJECTIVES: We aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19). METHODS: We performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from 22 February to 3 April 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: Spo2 <93% with 100% Fio2, respiratory rate >30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, ß-coefficients were used to develop a risk score. Trial Registration NCT04316949. RESULTS: We analysed 1113 patients (644 derivation, 469 validation cohort). Mean (±SD) age was 65.7 (±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in the derivation and validation cohorts, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years (OR 2.74; 95% CI 1.66-4.50), obesity (OR 4.62; 95% CI 2.78-7.70), body temperature ≥38°C (OR 1.73; 95% CI 1.30-2.29), respiratory rate ≥22 breaths/min (OR 3.75; 95% CI 2.01-7.01), lymphocytes ≤900 cells/mm3 (OR 2.69; 95% CI 1.60-4.51), creatinine ≥1 mg/dL (OR 2.38; 95% CI 1.59-3.56), C-reactive protein ≥10 mg/dL (OR 5.91; 95% CI 4.88-7.17) and lactate dehydrogenase ≥350 IU/L (OR 2.39; 95% CI 1.11-5.11). Assigning points to each variable, an individual risk score (PREDI-CO score) was obtained. Area under the receiver-operator curve was 0.89 (0.86-0.92). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 71.6% (65%-79%), 89.1% (86%-92%), 74% (67%-80%) and 89% (85%-91%), respectively. PREDI-CO score showed similar prognostic ability in the validation cohort: area under the receiver-operator curve 0.85 (0.81-0.88). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%-85%), 76% (70%-81%), 69% (60%-74%) and 85% (80%-89%), respectively. CONCLUSION: PREDI-CO score can be useful to allocate resources and prioritize treatments during the COVID-19 pandemic.

International electronic health record-derived COVID-19 clinical course profiles: the 4CE consortium.

We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.