Sustained cell-mediated but not humoral responses in rituximab-treated rheumatic patients after vaccination against SARS-CoV-2.

OBJECTIVES: B-cell depleting monoclonal antibodies are associated with increased COVID-19 severity and impaired immune response to vaccination. We aimed to assess the humoral and cell mediated (CMI) immune response after SARS-CoV-2 vaccination in rituximab (RTX)-treated rheumatic patients. METHODS: Serum and whole blood samples were collected from RTX-treated rheumatic patients 3-6 months after last vaccination against SARS-CoV-2. Serum was tested by ELISA for quantitative detection of anti-spike SARS-CoV-2 IgG. Cell-mediated variant-specific SARS-CoV-2 immunity (CMI) was assessed by interferon-γ release assay Covi-FERON FIA. Patients were interviewed for breakthrough COVID-19 infection (BTI) 3 months post sampling. RESULTS: Sixty patients were studied after a median (IQR) of 179 (117-221.5) days from last vaccine to sampling. Forty (66.7%) patients had positive Covi-FERON and 23 (38.3%) had detectable anti-spike IgG. Covi-FERON positive patients had lower median RTX cumulative dose [6 (4-10.75) vs 11 (6.75-14.75) grams, (P = 0.019)]. Patients with positive anti-spike IgG had received fewer RTX cycles [2 (2-4) vs 6 (4-8), P = 0.002] and cumulative dose [4 (3-7) vs 10 (6.25-13) grams, P = 0.002] and had shorter time from last vaccination to sampling [140 (76-199) vs 192 (128-230) days, P = 0.047]. Thirty-seven percent were positive only for Covi-FERON and 7% only for anti-spike IgG. Twenty (33.3%) BTI occurred post sampling, exclusively during Omicron variant predominance. The proportion of patients with CMI response against Delta variant was lower in patients who experienced BTI (25% vs 55%, P = 0.03). CONCLUSIONS: Four out of ten RTX-treated vaccinated patients show lasting cell-mediated immune response despite undetectable anti-spike antibodies. Cumulative RTX dose affects both humoral and cell-mediated responses to SARS-CoV-2 vaccines. Cell-mediated immune responses call for attention as a vaccine efficacy marker against SARS-CoV-2.

Covid Visual Assessment Scale ("Co.V.A.Sc."): quantification of COVID-19 disease extent on admission chest computed tomography (CT) in the prediction of clinical outcome-a retrospective analysis of 273 patients.

BACKGROUND: Admission chest CT is often included in COVID-19 patient management. PURPOSE: To evaluate the inter- and intraobserver variability of the Covid Visual Assessment Scale ("Co.V.A.Sc.") used for stratifying chest CT disease extent and to estimate its prospect to predict clinical outcomes. MATERIALS AND METHODS: This single-center, retrospective observational cohort study included all RT-PCR-confirmed COVID-19 adult patients undergoing admission chest CT, between 01/03/2021 and 17/03/2021. CTs were independently evaluated by two radiologists according to the "Co.V.A.Sc." (0: 0%, 1: 1-10%, 2: 11-25%, 3: 26-50%, 4: 51-75%, 5: > 75%). Patient demographics, laboratory, clinical, and hospitalization data were retrieved and analyzed in relation to the "Co.V.A.Sc." RESULTS: Overall, 273 patients (mean age 60.7 ± 14.8 years; 50.9% male) were evaluated. Excellent inter- and intraobserver variability was noted between the two independent radiologists' "Co.V.A.Sc." EVALUATIONS: "Co.V.A.Sc." classification (Exp(B) 0.391, 95%CI 0.212-0.719; p = 0.025) and patient age (Exp(B) 0.947, 95%CI 0.902-0.993; p = 0.25) were the only variables correlated with ICU admission, while age (Exp(B) 1.111, p = 0.0001), "Co.V.A.Sc." (Exp(B) 2.408; p = 0.002), and male gender (Exp(B) 3.213; p = 0.028) were correlated with in-hospital mortality. Specifically, for each "Co.V.A.Sc." unit increase, the probability of ICU admission increased by 1.47 times, and the probability of death increased by 11.1 times. According to ROC analysis, "Co.V.A.Sc." could predict ICU admission and in-hospital death with an optimal cutoff value of unit 3 (sensitivity 56.0%, specificity 84.3%) and unit 4 (sensitivity 41.9%, specificity 93.6%), respectively. CONCLUSION: "Co.V.A.Sc." upon hospital admittance seems to predict ICU admission and in-hospital death and could aid in optimizing risk-stratification and patient management.

A novel optical biosensor for the early diagnosis of sepsis and severe Covid-19: the PROUD study.

BACKGROUND: The accuracy of a new optical biosensor (OB) point-of-care device for the detection of severe infections is studied. METHODS: The OB emits different wavelengths and outputs information associated with heart rate, pulse oximetry, levels of nitric oxide and kidney function. At the first phase, recordings were done every two hours for three consecutive days after hospital admission in 142 patients at high-risk for sepsis by placing the OB on the forefinger. At the second phase, single recordings were done in 54 patients with symptoms of viral infection; 38 were diagnosed with COVID-19. RESULTS: At the first phase, the cutoff value of positive likelihood of 18 provided 100% specificity and 100% positive predictive value for the diagnosis of sepsis. These were 87.5 and 91.7% respectively at the second phase. OB diagnosed severe COVID-19 with 83.3% sensitivity and 87.5% negative predictive value. CONCLUSIONS: The studied OB seems valuable for the discrimination of infection severity.

Interdepartmental miscommunication regarding radiology: Addressing chronic challenges and exploring solutions.

Effective communication and collaboration among healthcare professionals are crucial for delivering high-quality patient care. Interdepartmental miscommunication poses a significant challenge to healthcare systems, potentially undermining the quality of healthcare services provided. In the same manner, communication barriers between referring physicians and radiologists can specifically affect radiology services and patient outcomes. This article attempts to put the spotlight on the ever-present chronic challenges of this issue and prompt readers to recognize the relevant potential pitfalls in their daily clinical practice. Practical solutions are explored and proposed, which should be tailored to the specific needs and issues that each individual institution may face.

Cytomegalovirus-Specific Hyperimmune Immunoglobulin Administration for Secondary Prevention after First-Trimester Maternal Primary Infection: A 13-Year Single-Center Cohort Study.

Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. The primary outcome was vertical transmission, defined as neonatal viruria or positive amniocentesis if pregnancy was discontinued. HIG, initially administered monthly and since 2019 biweekly, was discontinued in negative amniocentesis cases. Women declining amniocentesis and positive amniocentesis cases with normal sonography were offered monthly HIG until delivery as a treatment strategy. The total transmission rate was 29.9% (32/107; 10 pregnancy terminations with positive amniocentesis, 18 completed pregnancies with positive amniocentesis and 4 declining amniocentesis). Maternal viremia was the only factor associated with fetal transmission (OR 4.62, 95% CI 1.55-13.74). The transmission rate was not significantly different whether HIG was started during the first or second trimester (28.2% vs. 33.3%; p = 0.58), or between monthly and biweekly subgroups (25.7% vs. 37.8%, p = 0.193). Pre-treatment maternal viremia could inform decisions as a predictor of congenital infection.

Performance of point-of care molecular and antigen-based tests for SARS-CoV-2: a living systematic review and meta-analysis.

BACKGROUND: Molecular and antigen point-of-care tests (POCTs) have augmented our ability to rapidly identify and manage SARS-CoV-2 infection. However, their clinical performance varies among individual studies. OBJECTIVES: The evaluation of the performance of molecular and antigen-based POCTs in confirmed, suspected, or probable COVID-19 cases compared with that of laboratory-based RT-PCR in real-life settings. DATA SOURCES: MEDLINE/PubMed, Scopus, Embase, Web of Science, Cochrane Library, Cochrane COVID-19 study register, and COVID-19 Living Evidence Database from the University of Bern. STUDY ELIGIBILITY CRITERIA: Peer-reviewed or preprint observational studies or randomized controlled trials that evaluated any type of commercially available antigen and/or molecular POCTs for SARS-CoV-2, including multiplex PCR panels, approved by the United States Food and Drug Administration, with Emergency Use Authorization, and/or marked with Conformitè Europëenne from European Commission/European Union. PARTICIPANTS: Close contacts and/or patients with symptomatic and/or asymptomatic confirmed, suspected, or probable COVID-19 infection of any age. TEST/S: Molecular and/or antigen-based SARS-CoV-2 POCTs. REFERENCE STANDARD: Laboratory-based SARS-CoV-2 RT-PCR. ASSESSMENT OF RISK OF BIAS: Eligible studies were subjected to quality-control and risk-of-bias assessment using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. METHODS OF DATA SYNTHESIS: Summary sensitivities and specificities with their 95% CIs were estimated using a bivariate model. Subgroup analysis was performed when at least three studies informed the outcome. RESULTS: A total of 123 eligible publications (97 and 26 studies assessing antigen-based and molecular POCTs, respectively) were retrieved from 4674 initial records. The pooled sensitivity and specificity for 13 molecular-based POCTs were 92.8% (95% CI, 88.9-95.4%) and 97.6% (95% CI, 96.6-98.3%), respectively. The sensitivity of antigen-based POCTs pooled from 138 individual evaluations was considerably lower than that of molecular POCTs; the pooled sensitivity and specificity rates were 70.6% (95% CI, 67.2-73.8%) and 98.9% (95% CI, 98.5-99.2%), respectively. DISCUSSION: Further studies are needed to evaluate the performance of molecular and antigen-based POCTs in underrepresented patient subgroups and different respiratory samples.

Real-Life Effectiveness and Safety of Baricitinib as Adjunctive to Standard-of-Care Treatment in Hospitalized Patients With Severe Coronavirus Disease 2019.

BACKGROUND: Therapeutic options for hospitalized patients with severe coronavirus disease 2019 (sCOVID-19) are limited. Preliminary data have shown promising results with baricitinib, but real-life experience is lacking. We assessed the safety and effectiveness of add-on baricitinib to standard-of-care (SOC) including dexamethasone in hospitalized patients with sCOVID-19. METHODS: This study is a 2-center, observational, retrospective cohort study of patients with sCOVID-19, comparing outcomes and serious events between patients treated with SOC versus those treated with SOC and baricitinib combination. RESULTS: We included 369 patients with sCOVID-19 (males 66.1%; mean age 65.2 years; median symptom duration 6 days). The SOC was administered in 47.7% and combination in 52.3%. Patients treated with the combination reached the composite outcome (intensive care unit [ICU] admission or death) less frequently compared with SOC (22.3% vs 36.9%, P = .002). Mortality rate was lower with the combination in the total cohort (14.7% vs 26.6%, P = .005), and ICU admission was lower in patients with severe acute respiratory distress syndrome (29.7% vs 44.8%, P = .03). By multivariable analysis, age (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.36-2.44, per 10-year increase), partial pressure of oxygen/fraction of inspired oxygen ratio (OR = 0.60, 95% CI = .52-0.68, per 10 units increase), and use of high-flow nasal cannula (OR = 0.34; 95% CI, .16-0.74) were associated with the composite outcome, whereas baricitinib use was marginally not associated with the composite outcome (OR = 0.52; 95% CI, .26-1.03). However, baricitinib use was found to be significant after inverse-probability weighted regression (OR = 0.93; 95% CI, .87-0.99). No difference in serious events was noted between treatment groups. CONCLUSIONS: In real-life settings, addition of baricitinib to SOC in patients hospitalized with sCOVID-19 is associated with decreased mortality without concerning safety signals.

A case of encapsulating peritoneal sclerosis in a patient with chronic schistosomiasis.

Encapsulating peritoneal sclerosis (EPS) is a debilitating condition, mainly associated with long-term peritoneal dialysis, where up-regulation of intra-abdominal inflammatory pathways leads to a fibrocollagenous peritoneal membrane formation resembling a cocoon. EPS causes intestinal encapsulation leading to bowel obstruction and dilatation. Chronic schistosomiasis is characterized by dysregulation of pro-inflammatory and anti-inflammatory cytokines. EPS has never been reported before in patients with chronic schistosomiasis. We report the first, to our knowledge, case of a 57-year-old male originated from Burkina Faso with chronic intestinal and urogenital schistosomiasis and EPS. Although causality cannot be established solely by this case, we hypothesize that EPS may be the result of chronic inflammatory activation, due to immune dysregulation driven by chronic schistosomiasis. The potential pathogenetic linkage between these two conditions should be further explored.

Update in Viral Infections in the Intensive Care Unit.

The advent of highly sensitive molecular diagnostic techniques has improved our ability to detect viral pathogens leading to severe and often fatal infections that require admission to the Intensive Care Unit (ICU). Viral infections in the ICU have pleomorphic clinical presentations including pneumonia, acute respiratory distress syndrome, respiratory failure, central or peripheral nervous system manifestations, and viral-induced shock. Besides de novo infections, certain viruses fall into latency and can be reactivated in both immunosuppressed and immunocompetent critically ill patients. Depending on the viral strain, transmission occurs either directly through contact with infectious materials and large droplets, or indirectly through suspended air particles (airborne transmission of droplet nuclei). Many viruses can efficiently spread within hospital environment leading to in-hospital outbreaks, sometimes with high rates of mortality and morbidity, thus infection control measures are of paramount importance. Despite the advances in detecting viral pathogens, limited progress has been made in antiviral treatments, contributing to unexpectedly high rates of unfavorable outcomes. Herein, we review the most updated data on epidemiology, common clinical features, diagnosis, pathogenesis, treatment and prevention of severe community- and hospital-acquired viral infections in the ICU settings.

Chemotherapy resumption in ovarian cancer patient diagnosed with COVID-19.

•Chemotherapy resumption after convalescence from COVID-19 is safe and feasible.•No guidelines exist for resumption of chemotherapy in patients with COVID-19.•Cancer patients on chemotherapy may develop SARS-CoV-2 antibodies less frequently.

Clinical characteristics and outcomes of measles outbreak in adults: A multicenter retrospective observational study of 93 hospitalized adults in Greece.

OBJECTIVES: Measles outbreaks are increasingly reported among countries that were close-to-eliminate measles infection. There are few reports of clinical characteristics of measles in adults in the contemporary literature. In this study we aim to describe the clinical characteristics and complications of measles infection in hospitalized adults during the recent epidemic in Greece. METHODS: A multicentre observational retrospective study was conducted in three tertiary hospitals in Greece. All adult hospitalized patients (≥18 years old) with serologically confirmed and/or clinical features compatible with measles were included. Pediatric patients and patients with missing data were excluded. RESULTS: In total, 93 patients, 40 males (43 %) and 53 females (57 %), mostly young patients were included. Most of them (87 %) had no past medical history. Among women, 4 were pregnant. 56 (60.2 %) and 25 (26.9 %) patients reported either unknown or incomplete vaccination for measles. Ribavirin was administered in 8 (8.6 %) patients. Pneumonitis and hepatic involvement were the most common complications, occurring in 43 (46.2 %) and 75 (80.6 %) patients respectively. Pneumonitis was significantly associated with male sex, older age, lower lymphocyte counts and higher C-reactive protein (CRP) on admission. One pregnant woman suffered spontaneous fetal miscarriage and one patient died due to acute respiratory distress syndrome (ARDS) and high-risk pulmonary embolism. CONCLUSION: Considerable proportions of incompletely vaccinated or unvaccinated adults have led to the re-emergence of measles in countries with reported close-to-elimination rates. Pneumonitis is a major complication among adults with measles. More studies are imperative in order to explore the role of immune paresis in measles.

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study.

BACKGROUND: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. METHODS: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. FINDINGS: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9%) patients had a stroke-123(79%) ischaemic stroke, 27(17%) intracerebral/subarachnoid hemorrhage, and 6(4%) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5% among all centres in all countries, and 0.7% among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95% CI:1.1-3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95% CI:1.4-4.7, p = 0.006) were predictive of stroke. INTERPRETATION: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5%(pooled risk: 0.9%). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. FUNDING: None.