Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

/pdf/extrapulmonary-manifestations-of-covid-19-5gbdx3z1ea.pdf

Extrapulmonary manifestations of COVID-19.

Statistical Methods in Medical Research.

Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2. Clinical studies have also reported an association between COVID-19 and cardiovascular disease. Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism. Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern. In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system. By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.

/pdf/covid-19-and-cardiovascular-disease-from-basic-mechanisms-to-j7my2ihlv8.pdf

COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives.

Summary Background Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. Methods In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions. Findings 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70–86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. Interpretation In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included. Funding German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).

Neuropathology of patients with COVID-19 in Germany: a post-mortem case series.

"Body stuffing" and "Body packing" - Forensic control of human excrements in police custody in Hamburg, Germany.

Forensic anthropological examination and DNA analysis in the identification of human remains in Rwanda.

Impfstoffe gehoren zu den wirksamsten medizinischen Praventionsmasnahmen gegen Infektionserkrankungen. Trotz generell hoher Nutzen-Risiko-Relationen steigt in der offentlichen Wahrnehmung die Gefahr echter oder vermeintlicher Nebenwirkungen einer Impfung. Die Berichte hinsichtlich einer moglichen Assoziation zwischen einer Impfung und dem Auftreten von Autismus gelten aus wissenschaftlicher Sicht zwar als widerlegt. Trotzdem hat die Zahl erklarter Impfgegner, insbesondere in den USA oder in Grosbritannien, deutlich zugenommen. In jungster Zeit wurden auch Stimmen laut, die einen angeblichen Zusammenhang zwischen einer stattgehabten Impfung und dem Auftreten von Symptomen die als typisch fur ein so genanntes Schutteltrauma-Syndrome gelten, postulieren. Die vorliegende Arbeit untersucht die wissenschaftlichen Grundlagen dieser Behauptungen genauer.

Impfung und Schütteltrauma

Suffocation/Asphyxiation in ChildhoodDifferential Diagnosis to SIDS

Confronted with an emerging infectious disease, the medical community faced relevant concerns regarding the performance of autopsies of COVID-19 deceased at the beginning of the pandemic. This attitude has changed, and autopsies are now recognized as indispensable tools for elucidating COVID-19; despite this, the true risk of infection for autopsy staff is still debated. To elucidate the rate of SARS-CoV-2 contamination in personal protective equipment (PPE), swabs were taken at nine locations of the PPE of one physician and an assistant each from 11 full autopsies performed at four different centers. Further samples were obtained for three minimally invasive autopsies (MIA) conducted at a fifth center. Lung/bronchus swabs of the deceased served as positive controls. SARS-CoV-2 RNA was detected by RT-qPCR. In 9/11 full autopsies PPE samples were tested RNA positive with PCR, in total 21% of all PPE samples taken. The main contaminated parts of the PPE were the gloves (64% positive), the aprons (50% positive), and the upper sides of shoes (36% positive) while for example the fronts of safety goggles were only positive in 4.5% of the samples and all face masks were negative. In MIA, viral RNA was observed in one sample from a glove, but not in other swabs. Infectious virus isolation in cell culture was performed in RNA positive swabs from full autopsies. Of all RNA positive PPE samples, 21% of the glove samples were positive for infectious virus taken in 3/11 full autopsies. In conclusion, in >80% of autopsies, PPE was contaminated with viral RNA. In >25% of autopsies, PPE was found to be even contaminated with infectious virus, signifying a potential risk of infection among autopsy staff. Adequate PPE and hygiene measures, including appropriate waste deposition, are therefore mandatory to enable safe work environment.

/pdf/contamination-of-personal-protective-equipment-during-covid-4gyhe7bcbp.pdf

Jan-Peter Sperhake

Papers

"Body stuffing" and "Body packing" - Forensic control of human excrements in police custody in Hamburg, Germany.

Forensic anthropological examination and DNA analysis in the identification of human remains in Rwanda.

Impfung und Schütteltrauma

Suffocation/Asphyxiation in ChildhoodDifferential Diagnosis to SIDS

Contamination of personal protective equipment during COVID-19 autopsies