Alain Rudiger

Background/Objectives: Acute cor pulmonale is a critical clinical condition often encountered in acute care settings. Optimal management demands coordinated, interdisciplinary care. The aim of this study was to assess the current knowledge and management strategies for acute cor pulmonale among different groups of physicians involved in acute care in Switzerland. Methods: A structured questionnaire, extrapolated from the Acute Cardiovascular Care Association of the European Society of Cardiology clinical consensus statement on the diagnosis and treatment of cor pulmonale, was distributed among physicians of four specialties. Results: A total of 110 physicians participated in this multicenter survey, including 15 “experts,” 71 “generalists” (internal and emergency medicine), and 24 “specialists” (cardiology and intensive care). Experts validated 29 out of 40 questionnaire items (Fleiss Kappa 0.63), which were then used for analysis. Overall, there was substantial agreement with the experts’ answers among non-experts, with most correct response rates exceeding 60%. Significant differences were observed for only two items: experts more frequently recognized the prognostic value of clinical models (87% vs. 59%, p = 0.046) and the correct indications for systemic thrombolysis (100% vs. 76%, p = 0.037). Between generalists and specialists, differences in knowledge were minimal. Specialists more accurately identified the role of repeated arterial blood gas analysis, while generalists showed better awareness of clinical prognostic models. Conclusions: The study highlights a sound knowledge of acute cor pulmonale among acute care physicians, regardless of specialty. Despite comparable levels of knowledge, some variations reflect their clinical roles and information sources. The results emphasize the value of existing educational efforts and support the need for comprehensive, accessible guidelines to standardize care in complex conditions like acute cor pulmonale.

Die Zuweisung des 72-jährigen, ursprünglich aus Italien stammenden Patienten mit bekannter Leberzirrhose CHILD B erfolgte über den Hausarzt bei Adynamie, Hypotonie und Sklerenikterus zur internistischen Abklärung.

Un patient de 72 ans, originaire d’Italie et connu pour une cirrhose hépatique CHILD B, a été adressé par son médecin de famille pour un bilan de médecine interne en raison d’une adynamie, d’une hypotension et d’un ictère scléral.

Background: T‐cell lymphopenia and functional impairment is a hallmark of severe acute coronavirus disease 2019 (COVID‐19). How T‐cell numbers and function evolve at later timepoints after clinical recovery remains poorly investigated.Methods: We prospectively enrolled and longitudinally sampled 173 individuals with asymptomatic to critical COVID‐19 and analyzed phenotypic and functional characteristics of T cells using flow cytometry, 40‐parameter mass cytometry, targeted proteomics, and functional assays.Results: The extensive T‐cell lymphopenia observed particularly in patients with severe COVID‐19 during acute infection had recovered 6 months after infection, which was accompanied by a normalization of functional T‐cell responses to common viral antigens. We detected persisting CD4⁺ and CD8⁺ T‐cell activation up to 12 months after infection, in patients with mild and severe COVID‐19, as measured by increased HLA‐DR and CD38 expression on these cells. Persistent T‐cell activation after COVID‐19 was independent of administration of a COVID‐19 vaccine post‐infection. Furthermore, we identified a subgroup of patients with severe COVID‐19 that presented with persistently low CD8⁺ T‐cell counts at follow‐up and exhibited a distinct phenotype during acute infection consisting of a dysfunctional T‐cell response and signs of excessive pro‐inflammatory cytokine production.Conclusion: Our study suggests that T‐cell numbers and function recover in most patients after COVID‐19. However, we find evidence of persistent T‐cell activation up to 12 months after infection and describe a subgroup of severe COVID‐19 patients with persistently low CD8⁺ T‐cell counts exhibiting a dysregulated immune response during acute infection.

Background: Several autoimmune features occur during coronavirus disease 2019 (COVID‐19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID‐19.Methods: We performed highly sensitive indirect immunofluorescence assays to detect antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome‐wide serological profiling in a multicentric cohort of 175 COVID‐19 patients followed up to 1 year after infection, eleven vaccinated individuals, and 41 unexposed controls.Results: Compared with healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID‐19 and recovery. However, the paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID‐19. Furthermore, patients with severe COVID‐19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS‐CoV‐2‐specific antibody titers in COVID‐19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen‐specific humoral responses. Notably, the qualitative breadth of antibodies cross‐reactive with other coronaviruses was comparable in ANA‐positive and ANA‐negative individuals during acute COVID‐19. In autoantibody‐positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID‐19 and alterations of the B‐cell compartment after recovery.Conclusion: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS‐CoV‐2 infection, while the presence of autoantibodies in COVID‐19 patients correlated with increased antiviral humoral immune responses and inflammatory immune signatures.

Background Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. Objective We longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19. Methods We performed highly sensitive indirect immunofluorescence assays to detect anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed-up to one year after infection, eleven vaccinated individuals, and 41 unexposed controls. Results Compared to healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B cell compartment after recovery. Conclusion Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased anti-viral humoral immune responses and inflammatory immune signatures. Key messages - Acute COVID-19 patients exhibit transient autoantibody production, indicating a temporary loss of self-tolerance. - In COVID-19 patients, the presence of autoantibodies is associated with increased anti-viral humoral immune responses and inflammatory immune signatures that persist into recovery. Capsule Summary Autoantibodies in COVID-19 patients are transient and correlate with increased anti-viral humoral immune responses and an inflammatory immune signature persisting into recovery.

Early identification and isolation of SARS-CoV-2-infected individuals is central to contain the COVID-19 pandemic. Nasopharyngeal swabs (NPS) serve as a specimen for detection by RT-PCR and rapid antigen screening tests. Saliva has been confirmed as a reliable alternative specimen for RT-PCR and has been shown to be valuable for diagnosing children and in repetitive mass testing due to its non-invasive collection. Combining the advantages of saliva with those of antigen tests would be highly attractive to further increase test capacities. Here, we evaluated the performance of the Elecsys SARS-CoV-2 Antigen assay (Roche) in RT-PCR-positive paired NPS and saliva samples (N = 87) and unpaired NPS (N = 100) with confirmed SARS-CoV-2 infection (Roche cobas SARS-CoV-2 IVD test). We observed a high positive percent agreement (PPA) of the antigen assay with RT-PCR in NPS, reaching 87.2% across the entire cohort, whereas the overall PPA for saliva was insufficient (40.2%). At Ct values ≤ 28, PPA were 100% and 91.2% for NPS and saliva, respectively. At lower viral loads, the sensitivity loss of the antigen assay in saliva was striking. At Ct values ≤ 35, the PPA for NPS remained satisfactory (91.5%), whereas the PPA for saliva dropped to 46.6%. In conclusion, saliva cannot be recommended as a reliable alternative to NPS for testing with the Elecsys Anti-SARS-CoV-2 Antigen assay. As saliva is successfully used broadly in combination with RT-PCR testing, it is critical to create awareness that suitability for RT-PCR cannot be translated to implementation in antigen assays without thorough evaluation of each individual test system.

Rising demands for repetitive SARS-CoV-2 screens and mass testing necessitate additional test strategies. Saliva may serve as an alternative to nasopharyngeal swab (NPS) as its collection is simple, non-invasive and amenable for mass- and home testing, but its rigorous validation, particularly in children, is missing. We conducted a large-scale head-to-head comparison of SARS-CoV-2 detection by RT-PCR in saliva and NPS of 1270 adults and children reporting to outpatient test centers and an emergency unit. In total, 273 individuals were tested positive for SARS-CoV-2 in either NPS or saliva. SARS-CoV-2 RT-PCR results in the two specimens showed a high agreement (overall percent agreement = 97.8%). Despite lower viral loads in the saliva of both adults and children, detection of SARS-CoV-2 in saliva fared well compared to NPS (positive percent agreement = 92.5%). Importantly, in children, SARS-CoV-2 infections were more often detected in saliva than NPS (positive predictive value = 84.8%), underlining that NPS sampling in children can be challenging. The comprehensive parallel analysis reported here establishes saliva as a generally reliable specimen for the detection of SARS-CoV-2, with particular advantages for testing children, that is readily applicable to increase and facilitate repetitive and mass testing in adults and children.

Background A high volume of testing followed by rapid isolation and quarantine measures is critical to the containment of SARS-CoV-2. RT-PCR of nasopharyngeal swabs (NPS) has been established as sensitive gold standard for the detection of SARS-CoV-2 infection. Yet, additional test strategies are in demand to increase and broaden testing opportunities. As one attractive option, saliva has been discussed as an alternative to NPS as its collection is simple, non-invasive, suited for children and amenable for mass- and home-testing. Methods Here, we report on the outcome of a head-to-head comparison of SARS-CoV-2 detection by RT-PCR in saliva and nasopharyngeal swab (NPS) of 1187 adults and children reporting to outpatient test centers and an emergency unit for an initial SARS-CoV-2 screen. Results In total, 252 individuals were tested SARS-CoV-2 positive in either NPS or saliva. SARS-CoV-2 RT-PCR results in the two specimens showed a high agreement (Overall Percent Agreement = 98.0%). Despite lower viral loads in saliva, we observed sensitive detection of SARS-CoV-2 in saliva up to a threshold of Ct 33 in the corresponding NPS (Positive Percent Agreement = 97.7%). In patients with Ct above 33 in NPS, agreement rate dropped but still reaches notable 55.9%. Conclusion The comprehensive parallel analysis of NPS and saliva reported here establishes saliva as a reliable specimen for the detection of SARS-CoV-2 that can be readily added to the diagnostic portfolio to increase and facilitate testing. Key points Comparison with nasopharyngeal swabs in a large test center-based study shows that saliva is a reliable and convenient material for the detection of SARS-CoV-2 by RT-PCR in adults and children.