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

Summary Background A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1–3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding None.

Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study.

Summary Background Individuals admitted to hospital for COVID-19 might have persisting symptoms (so-called long COVID) and delayed complications after discharge. However, little is known regarding the risk for those not admitted to hospital. We therefore examined prescription drug and health-care use after SARS-CoV-2 infection not requiring hospital admission. Methods This was a population-based cohort study using the Danish prescription, patient, and health insurance registries. All individuals with a positive or negative RT-PCR test for SARS-CoV-2 in Denmark between Feb 27 and May 31, 2020, were eligible for inclusion. Outcomes of interest were delayed acute complications, chronic disease, hospital visits due to persisting symptoms, and prescription drug use. We used data from non-hospitalised SARS-CoV-2-positive and matched SARS-CoV-2-negative individuals from 2 weeks to 6 months after a SARS-CoV-2 test to obtain propensity score-weighted risk differences (RDs) and risk ratios (RRs) for initiation of 14 drug groups and 27 hospital diagnoses indicative of potential post-acute effects. We also calculated prior event rate ratio-adjusted rate ratios of overall health-care use. This study is registered in the EU Electronic Register of Post-Authorisation Studies (EUPAS37658). Findings 10 498 eligible individuals tested positive for SARS-CoV-2 in Denmark from Feb 27 to May 31, 2020, of whom 8983 (85·6%) were alive and not admitted to hospital 2 weeks after their positive test. The matched SARS-CoV-2-negative reference population not admitted to hospital consisted of 80 894 individuals. Compared with SARS-CoV-2-negative individuals, SARS-CoV-2-positive individuals were not at an increased risk of initiating new drugs (RD Interpretation The absolute risk of severe post-acute complications after SARS-CoV-2 infection not requiring hospital admission is low. However, increases in visits to general practitioners and outpatient hospital visits could indicate COVID-19 sequelae. Funding None.

Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study.

Abstract Background After almost 2 years of fighting against SARS-CoV-2 pandemic, the number of patients enduring persistent symptoms long after acute infection is a matter of concern. This set of symptoms was referred to as “long COVID”, and it was defined more recently as “Post COVID-19 condition” by the World health Organization (WHO). Although studies have revealed that long COVID can manifest whatever the severity of inaugural illness, the underlying pathophysiology is still enigmatic. Aim To conduct a comprehensive review to address the putative pathophysiology underlying the persisting symptoms of long COVID. Method We searched 11 bibliographic databases (Cochrane Library, JBI EBP Database, Medline, Embase, PsycInfo, CINHAL, Ovid Nursing Database, Journals@Ovid, SciLit, EuropePMC, and CoronaCentral). We selected studies that put forward hypotheses on the pathophysiology, as well as those that encompassed long COVID patients in their research investigation. Results A total of 98 articles were included in the systematic review, 54 of which exclusively addressed hypotheses on pathophysiology, while 44 involved COVID patients. Studies that included patients displayed heterogeneity with respect to the severity of initial illness, timing of analysis, or presence of a control group. Although long COVID likely results from long-term organ damage due to acute-phase infection, specific mechanisms following the initial illness could contribute to the later symptoms possibly affecting many organs. As such, autonomic nervous system damage could account for many symptoms without clear evidence of organ damage. Immune dysregulation, auto-immunity, endothelial dysfunction, occult viral persistence, as well as coagulation activation are the main underlying pathophysiological mechanisms so far. Conclusion Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. Apart from long-term organ damage, many hints suggest that specific mechanisms following acute illness could be involved in long COVID symptoms. KEY MESSAGES Long-COVID is a multisystem disease that develops regardless of the initial disease severity. Its clinical spectrum comprises a wide range of symptoms. The mechanisms underlying its pathophysiology are still unclear. Although organ damage from the acute infection phase likely accounts for symptoms, specific long-lasting inflammatory mechanisms have been proposed, as well. Existing studies involving Long-COVID patients are highly heterogeneous, as they include patients with various COVID-19 severity levels and different time frame analysis, as well.

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Pathophysiology and mechanism of long COVID: a comprehensive review

The novel SARS-CoV-2 coronavirus, which is responsible for COVID-19 disease, was first reported in Wuhan, China, in December of 2019. The virus rapidly spread, and the World Health Organization declared a pandemic by March 2020. With millions of confirmed cases worldwide, there is growing concern and considerable debate regarding the potential for coronavirus infection to contribute to an appreciable burden of chronic respiratory symptoms or fibrotic disease among recovered individuals. Because the first case of COVID-19 was documented less than one year ago, data regarding long-term clinical outcomes are not yet available, and predictions for long-term outcome are speculative at best. However, due to the staggering number of cases and the severity of disease in many individuals, there is a critical need to consider the potential long-term implications of COVID-19. This review examines current basic and clinical data regarding fibrogenic mechanisms of viral injury in the context of SARS-CoV-2. Several intersecting mechanisms between coronavirus infection and fibrotic pathways are discussed to highlight factors and processes that may be targetable to improve patient outcome. Reports of post-infection sequelae from previous coronavirus outbreaks are presented toward the goal of improved recognition of potential contributing risk factors for fibrotic disease.

https://journals.physiology.org/doi/pdf/10.1152/ajplung.00238.2020

Healing after COVID-19: are survivors at risk for pulmonary fibrosis?

Although pulmonary fibrosis can occur in the absence of a clear-cut inciting agent, and without a clinically clear initial acute inflammatory phase, it is more commonly associated with severe lung injury. This may be due to respiratory infections, chronic granulomatous diseases, medications, and connective tissue disorders. Pulmonary fibrosis is associated with permanent pulmonary architectural distortion and irreversible lung dysfunction. Available clinical, radiographic, and autopsy data has indicated that pulmonary fibrosis is central to severe acute respiratory distress syndrome (SARS) and MERS pathology, and current evidence suggests that pulmonary fibrosis could also complicate infection by SARS-CoV-2. The aim of this review is to explore the current literature on the pathogenesis of lung injury in COVID-19 infection. We evaluate the evidence in support of the putative risk factors for the development of lung fibrosis in the disease and propose risk mitigation strategies. We conclude that, from the available literature, the predictors of pulmonary fibrosis in COVID-19 infection are advanced age, illness severity, length of ICU stay and mechanical ventilation, smoking and chronic alcoholism. With no proven effective targeted therapy against pulmonary fibrosis, risk reduction measures should be directed at limiting the severity of the disease and protecting the lungs from other incidental injuries.

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Pulmonary Fibrosis in COVID-19 Survivors: Predictive Factors and Risk Reduction Strategies.

Objective The COVID-19 pandemic and annual influenza epidemic are responsible for thousands of deaths globally With a similarity in clinical as well as laboratory findings, there is a need to differentiate these two conditions on chest CT scan This paper attempts to use existing literature to draw out differences in chest CT findings in COVID-19 and influenza Methods A search was conducted using PubMed 17 original studies on chest CT findings in COVID-19 and influenza were identified for full-text review and data analysis Findings COVID-19 and influenza share similar chest CT findings The differences found show that COVID-19 ground-glass opacities are usually peripherally located with the lower lobes being commonly involved, while influenza has a central, peripheral, or random distribution usually affecting the five lobes Vascular engorgement, pleural thickening, and subpleural lines were reported in COVID-19 patients In contrast, pneumomediastinum and pneumothorax were reported only in studies on influenza Conclusion and Relevance COVID-19 and influenza have overlapping chest CT features with few differences which can assist in telling apart the two pathologies Additional studies are needed to further define the differences and degree between COVID-19 and influenza Copyright © 2020 Stephen O Onigbinde et al

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Chest Computed Tomography Findings in COVID-19 and Influenza: A Narrative Review

The emergence and spread of the highly contagious novel coronavirus disease (COVID-19) have triggered the greatest public health challenge of the last century. Aside from being a primary respiratory disease, acute ischemic stroke has emerged as a complication of the disease. While current evidence shows COVID-19 could cause ischemic stroke especially in severe disease, there are similarities in the risk factors for severe COVID-19 as well as ischemic stroke, underscoring the complex relationship between these two conditions. The pandemic has created challenges for acute stroke care. Rapid assessment and time-sensitive interventions required for optimum outcomes in acute stroke care have been complicated by COVID-19 due to the need for disease transmission preventive measures. The purpose of this article is to explore the putative mechanisms of ischemic stroke in COVID-19 and the clinical characteristics of COVID-19 patients who develop ischemic stroke. In addition, we discuss the challenges of managing acute ischemic stroke in the setting of COVID-19 and review current management guidelines. We also highlighted potential areas for future research.

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Acute Ischemic Stroke in COVID-19: Putative Mechanisms, Clinical Characteristics, and Management.

Endoscopic retrograde cholangiopancreatography (ERCP) is an important diagnostic and therapeutic procedure in the management of biliary and pancreatic disorders. Despite advances in ERCP facilities and techniques, pancreatitis remains the most common and feared complication of this procedure. The technical challenges of ERCP could be further compounded by variations in the configuration of the pancreatic ductal system. As a result, the knowledge of these variations and their potential role in the development of post-ERCP pancreatitis (PEP) is essential to any successful risk reduction strategy. This review provides an overview of the anatomy and embryological basis of pancreatic duct variations, as well as explore the different types and prevalence of these variations. Also, we discuss the mechanisms of PEP and provide evidence supporting a link between the variations and PEP using published data.

Pancreatic Duct Variations and the Risk of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

Background: Since the onset of the 2019 novel coronavirus disease (COVID-19), many reports have presented the disease as a respiratory disease, thereby limiting diagnosis to presentations with respiratory symptoms. This review critically analyzes and consolidates published literature describing extrapulmonary features of COVID-19.
Methods: Recently published full-text literature on the extrapulmonary manifestations of COVID-19 was reviewed. The studies reviewed focused on the cardiovascular, gastrointestinal, nervous, hematopoietic, genitourinary, and musculoskeletal systems; and ocular, otorhinolaryngological, and cutaneous symptoms.
Results: A total of 28 original articles were selected and analyzed. The most common extrapulmonary manifestations were acute cardiac injury (7.2-19.7%), arrhythmia (16.7%), and shock (8.7%) in the cardiovascular system; anorexia (83.8%), liver abnormality (14.8-37.2%), diarrhea (3.8-29.3%), abdominal pain (0.4-12.0%), nausea (9.5%), and vomiting (0.8-5.0%) in the gastrointestinal system; acute cerebrovascular disease and loss of consciousness (36.4%) in the nervous system; lymphopenia (40.0%-64.0), leukocytosis (14.3-23.4%), anemia (15.0%), thrombocytopenia (7.0%), elevated D-dimer (42.0%), and prolonged prothrombin time (2.1-6.0%) in the hematopoietic system; and proteinuria (43.9-62.7%), hematuria (26.7%), elevated urea (27.1%) and creatinine (18.6%), and acute kidney injury (3.6-5.1%) in the urinary system. Others include sore throat (28.6%), erythematous rash (15.9%), arthralgia/myalgia (14.8%), widespread urticaria (3.4%), and singular reports of acute myopericarditis, acute lymphocytic myocarditis, meningitis, viral encephalitis, testicular pain, anosmia, and acute conjunctivitis.
Conclusion: COVID-19 affects every organ-system and can cause extrapulmonary symptoms with or without respiratory symptoms. A high index of suspicion is required to help healthcare providers achieve early diagnosis, prompt treatment, and reduce the chances of spreading the disease within the community.

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Ademola S. Ojo

Papers

Pulmonary Fibrosis in COVID-19 Survivors: Predictive Factors and Risk Reduction Strategies.

Chest Computed Tomography Findings in COVID-19 and Influenza: A Narrative Review

Acute Ischemic Stroke in COVID-19: Putative Mechanisms, Clinical Characteristics, and Management.

Pancreatic Duct Variations and the Risk of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

A Review of the Extrapulmonary Manifestations of the 2019 Novel Coronavirus Disease (COVID-19)