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.

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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.

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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.

Eine 25-jahrige Frau mit Asperger-Syndrom und eine 27-jahrige Frau mit einem Sotos-Syndrom litten an einer chronischen Obstipation und verstarben plotzlich. Bei der auseren Besichtigung fielen in beiden Fallen massiv geblahte Bauchdecken auf. Die nachfolgenden computertomographischen Untersuchungen sowie die Sektionen zeigten grose Kotsteine, die auf zwei unterschiedliche Weisen zum Tode fuhrten.

Zwei plötzliche Todesfälle bei chronischer Obstipation

Kasuistisch vorgestellt wird ein ausergewohnlich schwerer Fall einer todlichen Misshandlung eines 2,5 Monate alten Sauglings durch einen vierjahrigen Jungen. Aus vordergrundiger Eifersucht auf das seiner Mutter fur 2 Tage zur Aufsicht uberlassene Baby, vor dem Hintergrund massiver Bindungslosigkeit und Verwahrlosung, schleuderte er dieses mehrfach mit dem Kopf gegen eine Wand sowie auch mehrfach auf den Fusboden. Der Saugling erlitt ein massives Schadel-Hirn-Trauma und verstarb wenige Stunden spater infolge des ausgepragten Hirnodems. Die Ermittlungen der Polizei in Kombination mit stets gleich bleibenden, detaillierten Einlassungen des Vierjahrigen liesen zu keinem Zeitpunkt Zweifel an der Taterschaft des Kindes aufkommen. Erst 5 Jahre nach der Tat wurde der mittlerweile zehnjahrige Tater erstmalig einer kinderpsychiatrischen Exploration unterzogen.

Tödliche Misshandlung eines Säuglings durch ein vierjähriges Kind

The incidence of sudden infant death syndrome (SIDS) has declined substantially, but the proportion of sudden unexpected death in infancy (SUDI) in neonates, <7 days old, has increased among all SUDI cases in the first year of life. The aim of this study was to analyze circumstances and common features of SUDI cases during the first 7 days of life. Data have been gathered retrospectively from Departments of Legal Medicine in Germany and Austria by using a standardized questionnaire. 19 out of 46 children died within 24 h after birth. A possible reason for this could be a lack of awareness of the needs of the newborn on the part of an exhausted mother. Fifty-two percent of the incidents occurred while the mother and her newborn were still hospitalized in a birth clinic. Forty-eight percent of the infants had been sleeping in the parents’ bed with mother and/or father. In 11 % of the cases, there was a sofa-sharing situation. Bed-sharing seems to increase the risk for SIDS in the newborn period as well as the risk for accidental suffocation/asphyxia of the baby. Therefore, mothers should not be instructed to bed-share. Particularly during the first 24 h after birth, it may be advisable to check mothers and infants regularly.

Sudden unexpected death in infancy (SUDI) in the early neonatal period: The role of bed-sharing

The postmortem examination prior to cremation: Still a necessary safety measure?

Sudden infant death syndrome (SIDS) is the sudden unexpected death of an infant < 1 year of age that remains unexplained after comprehensive workup including complete autopsy and investigation of the circumstances of death. The triple risk hypothesis posits that SIDS results as a combination of both intrinsic and extrinsic factors on the background of a predisposing vulnerability. Neuropathological examination in the past has focussed mainly on the brainstem as the major player in respiratory control, where subtle findings have been linked to the chain of events leading to death in SIDS. The cerebellum has received less attention, probably due to an assumed negligible role in central cardiorespiratory control. We report four cases of SIDS in which neuropathological investigation revealed cerebellar heterotopia of infancy, a distinct malformation of the cerebellum, and discuss the potential impact of this condition on the aetiology and pathogenesis of SIDS.

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Jan-Peter Sperhake

Papers

Zwei plötzliche Todesfälle bei chronischer Obstipation

Tödliche Misshandlung eines Säuglings durch ein vierjähriges Kind

Sudden unexpected death in infancy (SUDI) in the early neonatal period: The role of bed-sharing

The postmortem examination prior to cremation: Still a necessary safety measure?

Cerebellar heterotopia of infancy in sudden infant death syndrome: an observational neuropathological study of four cases