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Analyses of infection chains have demonstrated that severe acute respiratory syndrome coronavirus 2 is highly transmissive. However, data on postmortem stability and infectivity are lacking. Our finding of nasopharyngeal viral RNA stability in 79 corpses showed no time-dependent decrease. Maintained infectivity is supported by virus isolation up to 35 hours postmortem.

IntroductionThe alarmin IL-33 has been implicated in the pathology of immune-mediated liver diseases. IL-33 activates regulatory T cells (Tregs) and type 2 innate lymphoid cells (ILC2s) expressing the IL-33 receptor ST2. We have previously shown that endogenous IL-33/ST2 signaling activates ILC2s that aggravate liver injury in murine immune-mediated hepatitis. However, treatment of mice with exogenous IL-33 before induction of hepatitis ameliorated disease severity. Since IL-33 induces expression of amphiregulin (AREG) crucial for Treg function, we investigated the immunoregulatory role of the ST2+ Treg/AREG axis in immune-mediated hepatitis.MethodsC57BL/6, ST2-deficient (Il1rl1-/-) and Areg-/- mice received concanavalin A to induce immune-mediated hepatitis. Foxp3Cre+ x ST2fl/fl mice were pre-treated with IL-33 before induction of immune-mediated hepatitis. Treg function was assessed by adoptive transfer experiments and suppression assays. The effects of AREG and IL-33 on ST2+ Tregs and ILC2s were investigated in vitro . Immune cell phenotype was analyzed by flow cytometry.Results and discussionWe identified IL-33-responsive ST2+ Tregs as an effector Treg subset in the murine liver, which was highly activated in immune-mediated hepatitis. Lack of endogenous IL-33 signaling in Il1rl1-/- mice aggravated disease pathology. This was associated with reduced Treg activation. Adoptive transfer of exogenous IL-33-activated ST2+ Tregs before induction of hepatitis suppressed inflammatory T-cell responses and ameliorated disease pathology. We further showed increased expression of AREG by hepatic ST2+ Tregs and ILC2s in immune-mediated hepatitis. Areg-/- mice developed more severe liver injury, which was associated with enhanced ILC2 activation and less ST2+ Tregs in the inflamed liver. Exogenous AREG suppressed ILC2 cytokine expression and enhanced ST2+ Treg activation in vitro . In addition, Tregs from Areg-/- mice were impaired in their capacity to suppress CD4+ T-cell activation in vitro . Moreover, application of exogenous IL-33 before disease induction did not protect Foxp3Cre+ x ST2fl/fl mice lacking ST2+ Tregs from immune-mediated hepatitis. In summary, we describe an immunoregulatory role of the ST2+ Treg/AREG axis in immune-mediated hepatitis, in which AREG suppresses the activation of hepatic ILC2s while maintaining ST2+ Tregs and reinforcing their immunosuppressive capacity in liver inflammation.

We performed autopsies on persons in Germany who died from COVID-19 and observed higher nasopharyngeal SARS-CoV-2 viral loads for variants of concern (VOC) compared with non-VOC lineages. Pulmonary inflammation and damage appeared higher in non-VOC than VOC lineages until adjusted for vaccination status, suggesting COVID-19 vaccination may mitigate pulmonary damage.

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality. Accurate information on the specific circumstances of death and whether patients died from or with SARS-CoV-2 is scarce. To distinguish COVID-19 from non-COVID-19 deaths, we performed a systematic review of 735 SARS-CoV-2-associated deaths in Hamburg, Germany, from March to December 2020, using conventional autopsy, ultrasound-guided minimally invasive autopsy, postmortem computed tomography and medical records. Statistical analyses including multiple logistic regression were used to compare both cohorts. 84.1% (n = 618) were classified as COVID-19 deaths, 6.4% (n = 47) as non-COVID-19 deaths, 9.5% (n = 70) remained unclear. Median age of COVID-19 deaths was 83.0 years, 54.4% were male. In the autopsy group (n = 283), the majority died of pneumonia and/or diffuse alveolar damage (73.6%; n = 187). Thromboses were found in 39.2% (n = 62/158 cases), pulmonary embolism in 22.1% (n = 56/253 cases). In 2020, annual mortality in Hamburg was about 5.5% higher than in the previous 20 years, of which 3.4% (n = 618) represented COVID-19 deaths. Our study highlights the need for mortality surveillance and postmortem examinations. The vast majority of individuals who died directly from SARS-CoV-2 infection were of advanced age and had multiple comorbidities.

People experiencing homelessness (PEH) are at risk of contracting and transmitting infectious diseases. Data on PEH blood-transmitted virus prevalence and vaccination coverage is needed to design targeted interventions. A nationwide multicentre cross-sectional study of PEH was conducted. Clinical data were collected through questionnaire-based interviews, and blood samples were tested by serology and qPCR. Latent class analysis (LCA) identified subgroups of PEH, while univariable regressions identified risk factors of viral hepatitis. 643 PEH from four metropolitan areas in Germany were included. LCA revealed national short-term, long-term and international short-term PEH subgroups. The prevalence of anti-HAV-IgG, anti-HBc, anti-HBsAg, anti-HCV, anti-HEV and anti-HIV was 44% (95%CI: 39–48%), 17% (95%CI: 14–21%), 25% (95%CI: 21–29%), 18% (95%CI: 15–22%), 29% (95%CI: 25–33%) and 0.7% (95%CI: 0.2–1.7%), respectively. Active HBV and HCV infection was detected in 1.4% (95%CI: 0.7–2.7%) and 12% (95%CI: 9.6–14%), respectively. Univariable logistic regression revealed PEH with former imprisonment had 13.24 times the odds of active or past HCV infection (95%CI: 6.28–27.90) that individuals without had. This study shows the high acquisition and transmission risks for HCV/HIV among PEH. Low vaccination coverage for HAV/HBV calls for revising vaccine recommendations. High HCV infection risk associated with imprisonment highlights the need to address health disparities faced by incarcerated individuals.

We investigated the infectivity of 128 severe acute respiratory disease coronavirus 2-associated deaths and evaluated predictive values of standard diagnostic procedures. Maintained infectivity (20%) did not correlate with viral RNA loads but correlated well with anti-S antibody levels. Sensitivity >90% for antigen-detecting rapid diagnostic tests supports their usefulness for assessment.

Background To identify the determinants of health care use among homeless individuals. Methods Data were taken from the Hamburg survey of homeless individuals ( n  = 100 individuals in the here used model, mean age 44.8 years, SD 12.5) focusing on homeless individuals in Hamburg, Germany. The number of physician visits in the past 3 months and hospitalization in the preceding 12 months were used as outcome measures. Drawing on the Andersen model of health care use as a conceptual framework, predisposing characteristics, enabling resources and need factors as well as psychosocial variables were included as correlates. Results Negative binomial regressions showed that increased physician visits were associated with being female (IRR: 4.02 [95% CI: 1.60–10.11]), absence of chronic alcohol consume (IRR: 0.26 [95% CI: 0.12–0.57]) and lower health-related quality of life (IRR: 0.97 [95% CI: 0.96–0.98]). Furthermore, logistic regressions showed that the likelihood of hospitalization was positively associated with lower age (OR: 0.93 [95% CI: 0.89–0.98]), having health insurance (OR: 8.11 [2.11–30.80]) and lower health-related quality of life (OR: 0.97 [95% CI: 0.94–0.99]). Conclusions Our study showed that predisposing characteristics (both age and sex), enabling resources (i.e., health insurance) and need factors in terms of health-related quality of life are main drivers of health care use among homeless individuals. This knowledge may assist in managing health care use.

Critically ill COVID-19 patients are at high risk for venous thromboembolism (VTE), namely deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and death. The optimal anticoagulation strategy in critically ill patients with COVID-19 remains unknown. This study investigated the ante mortem incidence as well as postmortem prevalence of VTE, the factors predictive of VTE, and the impact of changed anticoagulation practice on patient survival. We conducted a consecutive retrospective analysis of postmortem COVID-19 (n = 64) and non-COVID-19 (n = 67) patients, as well as ante mortem COVID-19 (n = 170) patients admitted to the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Baseline patient characteristics, parameters related to the intensive care unit (ICU) stay, and the clinical and autoptic presence of VTE were evaluated and statistically compared between groups. The occurrence of VTE in critically ill COVID-19 patients is confirmed in both ante mortem (17%) and postmortem (38%) cohorts. Accordingly, comparing the postmortem prevalence of VTE between age- and sex-matched COVID-19 (43%) and non-COVID-19 (0%) cohorts, we found the statistically significant increased prevalence of VTE in critically ill COVID-19 cohorts (p = 0.001). A change in anticoagulation practice was associated with the statistically significant prolongation of survival time (HR: 2.55, [95% CI 1.41–4.61], p = 0.01) and a reduction in VTE occurrence (54% vs. 25%; p = 0.02). In summary, in the autopsy as well as clinical cohort of critically ill patients with COVID-19, we found that VTE was a frequent finding. A change in anticoagulation practice was associated with a statistically significantly prolonged survival time.

SARS-CoV-2-mediated acute kidney injury might be explained by indirect factors (eg, cytokine-mediated injury) and by direct viral infection and replication in kidney epithelial cells.4 We isolated SARS-CoV-2 from an autopsied kidney, which produced a 1000-times increase in viral RNA after 48 h of cell infection in vitro (figure; appendix p 1), thus confirming the presence of infective virus in the kidney, even under post-mortem conditions. Furthermore, we found that patient-derived SARS-CoV-2 replicates in non-human primate kidney tubular epithelial cells (the main cellular target of acute kidney injury) using indirect immunofluorescence imaging of SARS-CoV-2 non-structural protein 3, one of the SARS-CoV replicase cleaving products (appendix p 5).5 Our findings indicate that SARS-CoV-2 renal tropism is associated with disease severity (ie, premature death) and development of acute kidney injury. TBH reports grants from the German Research Foundation (CRC/1192, HU 1016/8-2, HU 1016/11-1, HU 1016/12-1), the Federal Ministry of Education and Research (STOP-FSGS-01GM1518C), and the European Research Council (grant 616891) during the study; grants and personal fees from Fresenius Medical Care; grants from Amicus Therapeutics and Sanofi Genzyme; and personal fees from Boehringer Ingelheim, Goldfinch Bio, Novartis Pharma, DaVita Germany, and Bayer Vital, unrelated to this Correspondence.