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

Clinical manifestations of COVID-19 are varied in the general population. This study aimed to systematize the literature regarding clinical manifestations of patients with confirmed COVID-19. A systematic review of the literature was conducted. A total of 8070 scientific productions were found in the databases. Among the studies, 184 met the initial inclusion criteria, with a total of 114,046 patients. After complete reading, 32 studies that did not report clinical manifestations were excluded. The 152 publications finally included a total of 41,409 individuals from at least 23 countries and 26 different clinical manifestations were reported. In percentage terms, 6 symptoms had a general prevalence greater than or equal to 25%, namely, fever (58.66%), cough (54.52%), dyspnea (30.82%), malaise (29.75%), fatigue (28.16%) and sputum/secretion (25.33%). Neurological symptoms (20.82%), dermatological manifestations (20.45%), anorexia (20.26%), myalgia (16.9%), sneezing (14.71%), sore throat (14.41%), rhinitis (14.29%), goosebumps (13.49%), headache (12.17%), chest pain (11.49%) and diarrhea (9.59%) were other common symptoms. Only one study reported dermatological manifestations. The least frequent sign/symptom was hemoptysis (1.65%). In studies with more than 100 patients, the 3 main symptoms were fever (57.93%), cough (54.21%), and dyspnea (30.64%). Dermatological manifestations do not appear among the main symptoms. The identification of all clinical manifestations of COVID-19 is essential for an early diagnosis and the adoption of preventive measures.

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Clinical manifestations of COVID-19 in the general population: systematic review.

Abstract Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin‐converting enzyme 2 or indirectly by promoting excessive inflammation in the body. The immune system is a critical factor in antiviral immunity and disease progression. In the context of SARS‐CoV‐2 infection, the immune system may become overly activated, resulting in a shift from regulatory to effector responses, which may subsequently promote the development and progression of autoimmune diseases. The incidence of autoimmune thyroid diseases, such as subacute thyroiditis, Graves' disease, and Hashimoto's thyroiditis, increases in individuals with COVID‐19 infection. This phenomenon may be attributed to aberrant responses of T‐cell subtypes, the presence of autoantibodies, impaired regulatory cell function, and excessive production of inflammatory cytokines, namely interleukin (IL)‐6, IL‐1β, interferon‐γ, and tumor necrosis factor‐α. Therefore, insights into the immune responses involved in the development of autoimmune thyroid disease according to COVID‐19 can help identify potential therapeutic approaches and guide the development of effective interventions to alleviate patients' symptoms. 

COVID‐19‐induced autoimmune thyroiditis: Exploring molecular mechanisms

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has created an immense menace to public health worldwide, exerting huge effects on global economic and political conditions. Understanding the biology and pathogenesis mechanisms of this novel virus, in large parts, relies on optimal physiological models that allow replication and propagation of SARS-CoV-2. Human organoids, derived from stem cells, are three-dimensional cell cultures that recapitulate the cellular organization, transcriptional and epigenetic signatures of their counterpart organs. Recent studies have indicated their great values as experimental virology platforms, making human organoid an ideal tool for investigating host–pathogen interactions. Here, we summarize research developments for SARS-CoV-2 infection of various human organoids involved in multiple systems, including lung, liver, brain, intestine, kidney and blood vessel organoids. These studies help us reveal the pathogenesis mechanism of COVID-19, and facilitate the development of effective vaccines and drugs as well as other therapeutic regimes.

/pdf/defense-of-covid-19-by-human-organoids-2vfln8e4tc.pdf

Defense of COVID-19 by Human Organoids

Little is known about the persistence of symptoms after clearance of SARS-CoV-2 infection. Our study aimed to assess persistent symptoms in COVID-19 patients after clearance of SARS-CoV-2 infection.A multi-center survey was conducted on first wave COVID-19 patients with confirmed SARS-CoV-2 infection. Sociodemographic and clinical characteristics, including presenting symptoms and persistent symptoms after viral clearance and possible factors contributing to persistence of such symptoms, were collected using an online multicomponent questionnaire. Descriptive and inferential statistical analysis was performed to detect the most persisting symptoms and factors contributing to their persistence.Overall, 538 patients were enrolled. Mean age was 41.17 (±SD 14.84), 54.1% were males, and 18.6% were smokers. Hypertension and diabetes were the most reported co-morbidities. Mild symptoms were reported in 61.3% of patients, 51.3% were admitted to hospital and 6.5% were admitted to the intensive care unit. Our study identified 49 types of persisting symptoms. Fatigue (59.1%), sense of fever (46.5%), anorexia (24.3%) and diarrhea (24.3%) were the most commonly reported persisting symptoms followed by loss of taste and smell (22.3%), headache (21.4%), cough (20.8) and dyspnea (21%). The use of hydroxychloroquine, azithromycin and multivitamins were significantly associated with persistence of symptoms (OR = 8.03, 8.89 and 10.12, respectively).Our study revealed that in COVID-19 recovered patients, many patients reported persistence of at least one symptom, particularly fatigue and sense of fever. Follow-up of patients after discharge from hospital is recommended until complete resolution of symptoms. 

Prevalence and Predictors of Persistent Symptoms After Clearance of SARS-CoV-2 Infection: A Multicenter Study from Egypt

Objective. Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, was first identified in December 2019 in Wuhan, China, and has since spread globally, resulting in an ongoing pandemic. However, the study of asymptomatic patients is still rare, and the understanding of its potential transmission risk is still insufficient. In this study, epidemiological investigations were conducted in the Zhejiang province to understand the epidemiology and clinical characteristics of asymptomatic patients with COVID-19. Methods. This retrospective study was carried out on 22 asymptomatic patients and 234 symptomatic patients with COVID-19 who were hospitalized in Zhejiang Duodi Hospital from January 21 to March 16, 2020. The characteristics of epidemiology, demography, clinical manifestations, and laboratory data of mild patients were compared and analyzed. Results. The median age was 28 years in asymptomatic patients and 48 years in symptomatic patients. The proportion who were female was 77.3% in asymptomatic patients and 36.3% in symptomatic patients ( ). The proportion of patients with coexisting diseases was 4.5% in asymptomatic patients and 38.0% in symptomatic patients ( ). The proportion of patients with increased CRP was 13.6% in the asymptomatic group and 61.1% in the symptomatic group ( ). The proportion of patients received antiviral therapy was 45.5% in the asymptomatic group and 97.9% in the symptomatic group ( ). The proportion of patients received oxygen therapy was 22.7% in the asymptomatic group and 99.1% in symptomatic patients ( ). By March 16, 2020, all patients were discharged from the hospital, and no symptoms had appeared in the asymptomatic patients during hospitalization. The median course of infection to discharge was 21.5 days in asymptomatic patients and 22 days in symptomatic patients. Conclusions. Asymptomatic patients are also infectious; relying only on clinical symptoms, blood cell tests, and radiology examination will lead to misdiagnosis of most patients, leading to the spread of the virus. Investigation of medical history is the best strategy for screening asymptomatic patients, especially young people, women, and people without coexisting disease, who are more likely to be asymptomatic when infected. Although the prognosis is good, isolation is critical for asymptomatic patients, and it is important not to end isolation early before a nucleic acid test turns negative.

/pdf/clinical-characteristics-of-asymptomatic-patients-with-sars-1lce5pe6bq.pdf

Clinical Characteristics of Asymptomatic Patients with SARS-CoV-2 in Zhejiang: An Imperceptible Source of Infection

/pdf/clinical-features-of-64-patients-outside-hubei-with-covid-19-3gr1p9u41u.pdf

Clinical features of 64 patients (outside Hubei) with COVID-19 in Wenzhou, China.

This study mainly focuses on revealing the role of PLAGL2 in lung cancer stemness. In vitro and in vivo experiments were performed to evaluate the effects of PLAGL2 on lung cancer cell stemness. Mechanistic analysis using luciferase reporter and ChIP assays were implemented to reveal the underlying mechanisms. The transcriptional factor E2F1 transcriptionally activated PLAGL2 expression via directly binding to PLAGL2 promoter in lung cancer cells. Moreover, PLAGL2 promoted the stemness of lung cancer cells dependent on E2F1‐mediated transcriptional activation. This study provides a potential target for lung cancer progression.

PLAGL2 promotes the stemness and is upregulated by transcription factor E2F1 in human lung cancer

[This corrects the article DOI: 10.1155/2020/2045341.].

/pdf/corrigendum-to-clinical-characteristics-of-asymptomatic-2m837z7z.pdf

Corrigendum to “Clinical Characteristics of Asymptomatic Patients with SARS-CoV-2 in Zhejiang: An Imperceptible Source of Infection”

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Clinical Characteristics of Asymptomatic Patients with SARS-CoV-2 in Zhejiang: An Imperceptible Source of Infection

Clinical features of 64 patients (outside Hubei) with COVID-19 in Wenzhou, China.

PLAGL2 promotes the stemness and is upregulated by transcription factor E2F1 in human lung cancer

Corrigendum to “Clinical Characteristics of Asymptomatic Patients with SARS-CoV-2 in Zhejiang: An Imperceptible Source of Infection”