ABSTRACT
Background A striking characteristic of Coronavirus Disease 2019(COVID-19) is the coexistence of clinically mild and severe cases. A comprehensive analysis of multiple risk factors predicting progression to severity is clinically meaningful. Methods The patients were classified into moderate and severe groups. The univariate regression analysis was used to identify their epidemiological and clinical features related to severity, which were used as possible risk factors and were entered into a forward-stepwise multiple logistic regression analysis to develop a multiple factor prediction model for the severe cases.Results 255 patients (mean age, 49.1±SD 14.6) were included, consisting of 184 (72.2%) moderate cases and 71 (27.8%) severe cases. The common symptoms were dry cough (78.0%), sputum (62.7%), and fever (59.2%). The less common symptoms were fatigue (29.4%), diarrhea (25.9%), and dyspnea (20.8%). The univariate regression analysis determined 23 possible risk factors. The multiple logistic regression identified seven risk factors closely related to the severity of COVID-19, including dyspnea, exposure history in Wuhan, CRP (C-reactive protein), aspartate aminotransferase (AST), calcium, lymphocytes, and age. The probability model for predicting the severe COVID-19 was P=1/1+exp (-1.78+1.02×age+1.62×high-transmission-setting-exposure +1.77×dyspnea+1.54×CRP+1.03×lymphocyte+1.03×AST+1.76×calcium). Dyspnea (OR=5.91) and hypocalcemia (OR=5.79) were the leading risk factors, followed by exposure to a high-transmission setting (OR=5.04), CRP (OR=4.67), AST (OR=2.81), decreased lymphocyte count (OR=2.80), and age (OR=2.78). Conclusions This quantitative prognosis prediction model can provide a theoretical basis for the early formulation of individualized diagnosis and treatment programs and prevention of severe diseases.
Subject(s)
Dyspnea , Fever , Hypocalcemia , COVID-19 , Fatigue , DiarrheaABSTRACT
Little is known regarding why a subset of COVID-19 patients exhibited prolonged positivity of SARS-CoV-2 infection. Here, we present a longitudinal sera proteomic resource for 37 COVID-19 patients over nine weeks, in which 2700 proteins were quantified with high quality. Remarkably, we found that during the first three weeks since disease onset, while clinical symptoms and outcome were indistinguishable, patients with prolonged disease course displayed characteristic immunological responses including enhanced Natural Killer (NK) cell-mediated innate immunity and regulatory T cell-mediated immunosuppression. We further showed that it is possible to predict the length of disease course using machine learning based on blood protein levels during the first three weeks. Validation in an independent cohort achieved an accuracy of 82%. In summary, this study presents a rich serum proteomic resource to understand host responses in COVID-19 patients and identifies characteristic Treg-mediated immunosuppression in LC patients, nominating new therapeutic target and diagnosis strategy.
Subject(s)
COVID-19ABSTRACT
ABSTRACT OBJECTIVE To investigate the dynamics of viral RNA, IgM, and IgG and their relationships in patients with SARS-CoV-2 pneumonia over an 8-week period. DESIGN Retrospective, observational case series. SETTING Wenzhou Sixth Peoples Hospital PARTICIPANTS Thirty-three patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to hospital. Data were collected from January 27 to April 10, 2020. MAIN OUTCOME MEASURES Throat swabs, sputum, stool, and blood samples were collected, and viral load was measured by reverse transcription PCR (RT-PCR). Specific IgM and IgG against spike protein (S), spike protein receptor binding domain (RBD), and nucleocapsid (N) were analyzed. RESULTS At the early stages of symptom onset, SARS-CoV-2 viral load is higher in throat swabs and sputum, but lower in stool. The median (IQR) time of undetectable viral RNA in throat swab, sputum, and stool was 18.5 (13.25-22) days, 22 (18.5-27.5) days, and 17 (11.5-32) days, respectively. In sputum, 17 patients (51.5%) had undetectable viral RNA within 22 days (short persistence), and 16 (48.5%) had persistent viral RNA more than 22 days (long persistence). Three patients (9.1%) had a detectable relapse of viral RNA in sputum within two weeks of their discharge from the hospital. One patient had persistent viral RNA for 59 days or longer. The median (IQR) seroconversion time of anti-S IgM, anti-RBD IgM, and anti-N IgM was 10.5 (7.75-15.5) days, 14 (9-24) days, and 10 (7-14) days, respectively. The median (IQR) seroconversion time of anti-S IgG, anti-RBD IgG, and anti-N IgG was 10 (7.25-16.5) days, 13 (9-17) days, and 10 (7-14) days, respectively. By week 8 after symptom onset, IgM were negative in many of the previously positive patients, and IgG levels remained less than 50% of the peak levels in more than 20% of the patients. In about 40% of the patients, anti-RBD IgG levels were 4-times higher in convalescence than in acute phase. SARS-CoV-2 RNA coexisted with antibodies for more than 50 days. Anti-RBD IgM and IgG levels, including anti-RBD IgM levels at presentation and peak time, were significantly higher in viral RNA short persistence patients than in long persistence patients. CONCLUSION This study adds important new information about the features of viral load and antibody dynamics of SARS-CoV-2. It is clear from these results that the viral RNA persists in sputum and stool specimens for a relatively long time in many patients. Anti-RBD may also serve as a potential protective antibody against SARS-CoV-2 infection, as viral persistence appears to be related to anti-RBD levels. Earlier treatment intervention also appears to be a factor in viral persistence.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Background: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel coronavirus COVID-19. Meanwhile, as the infection progressed, a large number of cases were also diagnosed in Wenzhou, China. The objective of the study is to describe the clinical laboratory features, especially lipid profile of the patients with COVID-19 infection in Wenzhou.Methods: All cases were in a designated hospital in Wenzhou, and confirmed by positive virial nucleic acid detection through PCR assay. All clinical laboratory data were from the first test results after their admission. The unpaired t test was used for data analysis.Findings: The absolute value of white blood cells, neutrophils and lymphocytes were lower than healthy controls ( P ＜0.05), more significantly, the patients had sharply decreased total cholesterol (TC), HDL-cholesterol and LDL-cholesterol levels ( P ＜0.001), 3.70±0.09mmol/L, 1.18±0.03 mmol/L and 1.82±0.08 mmol/L respectively, and increased monocyte/HDL-cholesterol ratio (0.37±0.02 vs 0.28±0.01 in healthy control). Among the patients, the primary infection cases showed the lower HDL-cholesterol levels (1.10±0.04 mmol/L) and higher monocyte/HDL-cholesterol ratio (0.43±0.03) than the secondary infection cases by person-to-person transmission ( P ＜0.05). Compared with the female patients, the male patients had higher levels of monocytes [(0.46±0.02) ×10 9 /L], M/HDL-C ratio (0.44±0.02), and lactate dehydrogenase (LDH, 257.6±12.32 U/l).Interpretation: Low serum cholesterol level in the patients with COVID-19 in Wenzhou, China. Altered serum cholesterol provide important information, and is meaningful to understand the disease.Funding Statement: This work is funded by Natural Science Foundation of Zhejiang Province (LQ18H020005). Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was authorized by Ethics Commission of Wenzhou Central Hospital.