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

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome). We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.

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Diverse Functional Autoantibodies in Patients with COVID-19.

The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-8. While pathological innate immune activation is well documented in severe disease1, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the "exoproteome"). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.

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Diverse Functional Autoantibodies in Patients with COVID-19

https://scholarlycommons.henryford.com/cgi/viewcontent.cgi?article=1179&context=hematologyoncology_articles

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) has rapidly developed into a pandemic. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID-19 patients. Therefore, the aim of this study was to determine the role of ferritin in COVID-19. METHODS: Studies investigating ferritin in COVID-19 were collected from PubMed, EMBASE, CNKI, SinoMed, and WANFANG. A meta-analysis was performed to compare the ferritin level between different patient groups: non-survivors versus survivors; more severe versus less severe; with comorbidity versus without comorbidity; ICU versus non-ICU; with mechanical ventilation versus without mechanical ventilation. RESULTS: A total of 52 records involving 10 614 COVID-19-confirmed patients between December 25, 2019, and June 1, 2020, were included in this meta-analysis, and 18 studies were included in the qualitative synthesis. The ferritin level was significantly increased in severe patients compared with the level in non-severe patients [WMD 397.77 (95% CI 306.51-489.02), P < .001]. Non-survivors had a significantly higher ferritin level compared with the one in survivors [WMD 677.17 (95% CI 391.01-963.33), P < .001]. Patients with one or more comorbidities including diabetes, thrombotic complication, and cancer had significantly higher levels of ferritin than those without (P < .01). Severe acute liver injury was significantly associated with high levels of ferritin, and its level was associated with intensive supportive care, including ICU transfer and mechanical ventilation. CONCLUSIONS: Ferritin was associated with poor prognosis and could predict the worsening of COVID-19 patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcla.23618

Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

The prognostic role of hypercoagulability in COVID-19 patients is ambiguous. D-dimer, may be regarded as a global marker of hemostasis activation in COVID-19. Our study was to assess the predictive value of D-dimer for the severity, mortality and incidence of venous thromboembolism (VTE) events in COVID-19 patients. PubMed, EMBASE, Cochrane Library and Web of Science databases were searched. The pooled diagnostic value (95% confidence interval [CI]) of D-dimer was evaluated with a bivariate mixed-effects binary regression modeling framework. Sensitivity analysis and meta regression were used to determine heterogeneity and test robustness. A Spearman rank correlation tested threshold effect caused by different cut offs and units in D-dimer reports. The pooled sensitivity of the prognostic performance of D-dimer for the severity, mortality and VTE in COVID-19 were 77% (95% CI: 73%-80%), 75% (95% CI: 65%-82%) and 90% (95% CI: 90%-90%) respectively, and the specificity were 71% (95% CI: 64%-77%), 83% (95% CI: 77%-87%) and 60% (95% CI: 60%-60%). D-dimer can predict severe and fatal cases of COVID-19 with moderate accuracy. It also shows high sensitivity but relatively low specificity for detecting COVID-19-related VTE events, indicating that it can be used to screen for patients with VTE.

https://journals.sagepub.com/doi/pdf/10.1177/10760296211010976

Diagnostic Value of D-Dimer in COVID-19: A Meta-Analysis and Meta-Regression

// Liubing Li 1, * , Qian Wang 1, * , Funing Yang 1, 2, * , Chanyuan Wu 1 , Si Chen 1, 3 , Xiaoting Wen 1 , Chenxi Liu 1 , Yongzhe Li 1 1 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China 2 Department of Medical Laboratory, The First Hospital of Jilin University, Changchun, China 3 Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing, China * These authors have contributed equally to this work Correspondence to: Yongzhe Li, email: yongzhelipumch@126.com Keywords: dermatomyositis, anti-MDA5, diagnosis, prognosis, marker Received: December 08, 2016      Accepted: February 13, 2017      Published: February 24, 2017 ABSTRACT The presence of anti-MDA5 antibodies in serum represents an important biomarker in the diagnosis and prediction of prognosis for patients with idiopathic inflammatory myopathies (IIMs). Due to conflicting results that have been reported regarding the detection of anti-MDA5 antibodies, the goal of this study was to assess a potential association between the presence of anti-MDA5 antibodies and dermatomyositis/polymyositis (DM/PM), as well as the diagnostic and prognostic values of anti-MDA5 antibodies for DM/PM. For this, a review of literature published prior to October 15, 2016 was conducted. Eight studies with 286 PM patients and 216 healthy controls and nine studies with 628 DM patients and 221 healthy controls were selected according to specific inclusion criteria. The outcomes of these studies revealed that the presence of anti-MDA5 antibodies was associated with DM, especially CADM, and not with PM. Furthermore, the pooled sensitivity, specificity, and area under the curve (AUC) values were 0.62 (95% confidence interval (CI): 0.52–0.70), 1.00 (95% CI: 0.97–1.00), and 0.9381 for CADM patients versus healthy controls when an immunoprecipitation method was used. The presence of anti-MDA5 antibodies was also found to be significantly associated with an increased risk of death in DM (relative risk = 3.32, 95% CI: 1.65–6.67, P = 0.001). These findings suggest that anti-MDA5 antibodies correlate with DM and could be used as a biomarker in the clinical diagnosis of CADM. The presence of anti-MDA5 antibodies was also associated with poor prognosis regarding the overall survival of patients with DM.

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Anti-MDA5 antibody as a potential diagnostic and prognostic biomarker in patients with dermatomyositis.

// Liubing Li 1, * , Qian Wang 1, * , Xiaoting Wen 1, * , Chenxi Liu 1, * , Chanyuan Wu 1 , Funing Yang 1, 2 , Xiaofeng Zeng 1 and Yongzhe Li 1 1 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China 2 Department of Medical Laboratory, The First Hospital of Jilin University, Changchun, China * These authors have contributed equally to this work Correspondence to: Yongzhe Li, email: yongzhelipumch@126.com Keywords: anti-MDA5, dermatomyositis, ILD, RPILD, diagnosis Received: March 13, 2017      Accepted: June 17, 2017      Published: July 06, 2017 ABSTRACT Anti-melanoma differentiation-associated protein 5 (MDA5) antibody have been found in dermatomyositis (DM)-associated interstitial lung disease (DM-ILD) and DM-associated rapidly progressive ILD (DM-RPILD). Due to the conflicting results regarding the association between anti-MDA5 antibody and DM-ILD or DM-RPILD and the diagnostic value of this antibody for DM-ILD and DM-RPILD, we performed this meta-analysis. A systematic search was performed to identify studies published to January 14, 2017. Sixteen publications with 491 DM with ILD versus 605 DM without ILD, as well as eighteen publications with 186 DM with RPILD and 790 DM without RPILD were included. The pooled sensitivity, specificity, and area under the curve (AUC) values of anti-MDA5 antibody for DM-ILD were 0.47 (95% CI: 0.37–0.57), 0.96 (95% CI, 0.92–0.97), and 0.90 (95% CI: 0.88–0.93), respectively, with a low sensitivity value. The pooled sensitivity, specificity, and AUC values were 0.83 (95% CI: 0.77–0.88), 0.86 (95% CI: 0.80–0.91), and 0.87 (95% CI: 0.84–0.90) for DM with RPILD versus without RPILD with good sensitivity and specificity values. Trial sequential analysis showed sufficient evidence to support that anti-MDA5 antibody was associated with DM-ILD and DM-RPILD. The statistical power of this study calculated using G*Power version 3.1.9.2 was more than 99% (α = 0.05). Taken together, these findings suggest that anti-MDA5 antibody has a potential useful ability as a noninvasive biomarker in the diagnosis of RPILD in patients with DM.

/pdf/assessment-of-anti-mda5-antibody-as-a-diagnostic-biomarker-3xm07jw96j.pdf

Assessment of anti-MDA5 antibody as a diagnostic biomarker in patients with dermatomyositis-associated interstitial lung disease or rapidly progressive interstitial lung disease.

Chenxi Liu

Papers

Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

Diagnostic Value of D-Dimer in COVID-19: A Meta-Analysis and Meta-Regression

Anti-MDA5 antibody as a potential diagnostic and prognostic biomarker in patients with dermatomyositis.

Assessment of anti-MDA5 antibody as a diagnostic biomarker in patients with dermatomyositis-associated interstitial lung disease or rapidly progressive interstitial lung disease.

Myositis-specific autoantibodies in dermatomyositis/polymyositis with interstitial lung disease.