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.

Key Clinical Points Mild or Moderate Covid-19 Covid-19 (the illness caused by SARS-CoV-2) has a range of clinical manifestations, including cough, fever, malaise, myalgias, gastrointestinal symptom...

https://www.nejm.org/doi/pdf/10.1056/NEJMcp2009249

Mild or Moderate Covid-19.

BACKGROUND: There is currently very limited information on the nature and prevalence of post-COVID-19 symptoms after hospital discharge. METHODS: A purposive sample of 100 survivors discharged from a large University hospital were assessed 4 to 8 weeks after discharge by a multidisciplinary team of rehabilitation professionals using a specialist telephone screening tool designed to capture symptoms and impact on daily life. EQ-5D-5L telephone version was also completed. RESULTS: Participants were between 29 and 71 days (mean 48 days) postdischarge from hospital. Thirty-two participants required treatment in intensive care unit (ICU group) and 68 were managed in hospital wards without needing ICU care (ward group). New illness-related fatigue was the most common reported symptom by 72% participants in ICU group and 60.3% in ward group. The next most common symptoms were breathlessness (65.6% in ICU group and 42.6% in ward group) and psychological distress (46.9% in ICU group and 23.5% in ward group). There was a clinically significant drop in EQ5D in 68.8% in ICU group and in 45.6% in ward group. CONCLUSIONS: This is the first study from the United Kingdom reporting on postdischarge symptoms. We recommend planning rehabilitation services to manage these symptoms appropriately and maximize the functional return of COVID-19 survivors.

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Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation.

Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA are frequently observed in COVID-19 patients. However, it is unclear whether SARS-CoV-2 replicates in the human intestine and contributes to possible fecal-oral transmission. Here, we report productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids. Expression of two mucosa-specific serine proteases, TMPRSS2 and TMPRSS4, facilitated SARS-CoV-2 spike fusogenic activity and promoted virus entry into host cells. We also demonstrate that viruses released into the intestinal lumen were inactivated by simulated human colonic fluid, and infectious virus was not recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression.

/pdf/tmprss2-and-tmprss4-promote-sars-cov-2-infection-of-human-2o89ln5oj4.pdf

TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes.

https://research.birmingham.ac.uk/portal/files/100722606/manu_lancet_GH_clean_4_16_copy.pdf

Lei Pan

Papers

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study.