A Predictive Nomogram for Predicting Improved Clinical Outcome Probability in Patients with COVID-19 in Zhejiang Province, China.

The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019 (COVID-19). Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected. Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients. The least absolute shrinkage and selection operator (LASSO) logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients. The concordance index (C-index) was used to assess the discrimination of the model, and internal validation was performed through bootstrap resampling. A novel predictive nomogram was constructed by incorporating these features. Of the 104 patients included in the study (median age 55 years), 75 (72.1%) had improved short-term outcomes, while 29 (27.9%) showed no signs of improvement. There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes. After a multi-step screening process, prognostic factors were selected and incorporated into the nomogram construction, including immunoglobulin A (IgA), C-reactive protein (CRP), creatine kinase (CK), acute physiology and chronic health evaluation II (APACHE II), and interaction between CK and APACHE II. The C-index of our model was 0.962 (95% confidence interval (CI), 0.931-0.993) and still reached a high value of 0.948 through bootstrapping validation. A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve. The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient, which may facilitate personalized counselling and treatment.

Clinical characteristics and clinical outcome of community clusters with SARS-CoV-2 infection.

Background: Community clustering is one of the main features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, few studies have been conducted on the clinical characteristics and clinical outcome of clustered cases and sporadic cases with COVID-19. Methods: We recruited 41 community clusters confirmed with SARS-CoV-2 infection compared with 49 sporadic cases in Zhejiang Province from 19 January 2020 to 9 June 2020. Clinical data were collected to evaluate the clinical outcome and characteristics of community clusters. Results: Compared to sporadic cases, clustered cases had significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II) score {5.0 [interquartile range (IQR), 2.0-7.5] vs. 7.0 [IQR, 4.0-12.5]; P = 0.005}, less members in intensive care unit (ICU) (6 [14.6%] vs. 18 [36.7%]; P = 0.018), and shorter time of viral shedding in fecal samples (18.5 [IQR, 17.0-28.3] vs. 32.0 [IQR, 24.3-35.5]; P = 0.002). Univariable logistic regression revealed that older age (odds ratios 1.078, 95% confidence intervals 1.007-1.154, per year increase; p = 0.032), high APACHE II score (3.171, 1.147-8.76; P = 0.026), elevated interleukin-2 levels (3.078, 1.145-8.279; P = 0.026) were associated with ICU admission of clustered cases. Conclusions: Compared to sporadic cases, clustered cases exhibited milder disease severity and a better clinical outcome, which may be closely related to the management of early detection, early diagnosis, early treatment and early isolation of COVID-19.

Clinical characteristics and clinical outcome of community clusters with SARS-CoV-2 infection

Background Community clustering is one of the main features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, few studies have been conducted on the clinical characteristics and clinical outcome of clustered cases and sporadic cases with COVID-19. Methods We recruited 41 community clusters confirmed with SARS-CoV-2 infection compared with 49 sporadic cases in Zhejiang Province from 19 January 2020 to 9 June 2020. Clinical data were collected to evaluate the clinical outcome and characteristics of community clusters. Results Compared to sporadic cases, clustered cases had significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II) score {5.0 [interquartile range (IQR), 2.0–7.5] vs. 7.0 [IQR, 4.0–12.5];P = 0.005}, less members in intensive care unit (ICU) (6 [14.6%] vs. 18 [36.7%];P = 0.018), and shorter time of viral shedding in fecal samples (18.5 [IQR, 17.0–28.3] vs. 32.0 [IQR, 24.3–35.5];P = 0.002). Univariable logistic regression revealed that older age (odds ratios 1.078, 95% confidence intervals 1.007–1.154, per year increase;p = 0.032), high APACHE II score (3.171, 1.147–8.76;P = 0.026), elevated interleukin-2 levels (3.078, 1.145–8.279;P = 0.026) were associated with ICU admission of clustered cases. Conclusions Compared to sporadic cases, clustered cases exhibited milder disease severity and a better clinical outcome, which may be closely related to the management of early detection, early diagnosis, early treatment and early isolation of COVID-19.

Characteristics of COVID-19 Patients With SARS-CoV-2 Positivity in Feces.

Background: SARS-CoV-2 is highly contagious and poses a great threat to epidemic control and prevention. The possibility of fecal-oral transmission has attracted increasing concern. However, viral shedding in feces has not been completely investigated. Methods: This study retrospectively reviewed 97 confirmed coronavirus disease 2019 (COVID-19) patients hospitalized at the First Affiliated Hospital, School of Medicine, Zhejiang University, from January 19 to February 17, 2020. SARS-CoV-2 RNA in samples of sputum, nasopharyngeal or throat swabs, bronchoalveolar lavage and feces was detected by real-time reverse transcription polymerase chain reaction (RT-PCR). Clinical characteristics and parameters were compared between groups to determine whether fecal RNA was positive. Results: Thirty-four (35.1%) of the patients showed detectable SARS-CoV-2 RNA in feces, and 63 (64.9%) had negative detection results. The median time of viral shedding in feces was approximately 25 days, with the maximum time reaching 33 days. Prolonged fecal-shedding patients showed longer hospital stays. Those patients for whom fecal viral positivity persisted longer than 3 weeks also had lower plasma B-cell counts than those patients in the non-prolonged group [70.5 (47.3-121.5) per µL vs. 186.5 (129.3-376.0) per µL, P = 0.023]. Correlation analysis found that the duration of fecal shedding was positively related to the duration of respiratory viral shedding (R = 0.70, P < 0.001) and negatively related to peripheral B-cell counts (R = -0.44, P < 0.05). Conclusions: COVID-19 patients who shed SARS-CoV-2 RNA in feces presented similar clinical characteristics and outcomes as those who did not shed SARS-CoV-2 RNA in feces. The prolonged presence of SARS-CoV-2 nucleic acids in feces was highly correlated with the prolonged shedding of SARS-CoV-2 RNA in the respiratory tract and with lower plasma B-cell counts.

Cytokine Signature Associated With Disease Severity in COVID-19.

Coronavirus disease 2019 (COVID-19) broke out and then became a global epidemic at the end of 2019. With the increasing number of deaths, early identification of disease severity and interpretation of pathogenesis are very important. Aiming to identify biomarkers for disease severity and progression of COVID-19, 75 COVID-19 patients, 34 healthy controls and 23 patients with pandemic influenza A(H1N1) were recruited in this study. Using liquid chip technology, 48 cytokines and chemokines were examined, among which 33 were significantly elevated in COVID-19 patients compared with healthy controls. HGF and IL-1ß were strongly associated with APACHE II score in the first week after disease onset. IP-10, HGF and IL-10 were correlated positively with virus titers. Cytokines were significantly correlated with creatinine, troponin I, international normalized ratio and procalcitonin within two weeks after disease onset. Univariate analyses were carried out, and 6 cytokines including G-CSF, HGF, IL-10, IL-18, M-CSF and SCGF-ß were found to be associated with the severity of COVID-19. 11 kinds of cytokines could predict the severity of COVID-19, among which IP-10 and M-CSF were excellent predictors for disease severity. In conclusion, the levels of cytokines in COVID-19 were significantly correlated with the severity of the disease in the early stage, and serum cytokines could be used as warning indicators of the severity and progression of COVID-19. Early stratification of disease and intervention to reduce hypercytokinaemia may improve the prognosis of COVID-19 patients.

One-year follow-up of chest CT findings in patients after SARS-CoV-2 infection.

BACKGROUND: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge. METHODS: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated. RESULTS: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores. CONCLUSION: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age.

The serum metabolome of COVID-19 patients is distinctive and predictive.

BACKGROUND: Metabolism is critical for sustaining life, immunity and infection, but its role in COVID-19 is not fully understood. METHODS: Seventy-nine COVID-19 patients, 78 healthy controls (HCs) and 30 COVID-19-like patients were recruited in a prospective cohort study. Samples were collected from COVID-19 patients with mild or severe symptoms on admission, patients who progressed from mild to severe symptoms, and patients who were followed from hospital admission to discharge. The metabolome was assayed using gas chromatography-mass spectrometry. RESULTS: Serum butyric acid, 2-hydroxybutyric acid, l-glutamic acid, l-phenylalanine, l-serine, l-lactic acid, and cholesterol were enriched in COVID-19 and COVID-19-like patients versus HCs. Notably, d-fructose and succinic acid were enriched, and citric acid and 2-palmitoyl-glycerol were depleted in COVID-19 patients compared to COVID-19-like patients and HCs, and these four metabolites were not differentially distributed in non-COVID-19 groups. COVID-19 patients had enriched 4-deoxythreonic acid and depleted 1,5-anhydroglucitol compared to HCs and enriched oxalic acid and depleted phosphoric acid compared to COVID-19-like patients. A combination of d-fructose, citric acid and 2-palmitoyl-glycerol distinguished COVID-19 patients from HCs and COVID-19-like patients, with an area under the curve (AUC) > 0.92 after validation. The combination of 2-hydroxy-3-methylbutyric acid, 3-hydroxybutyric acid, cholesterol, succinic acid, L-ornithine, oleic acid and palmitelaidic acid predicted patients who progressed from mild to severe COVID-19, with an AUC of 0.969. After discharge, nearly one-third of metabolites were recovered in COVID-19 patients. CONCLUSIONS: The serum metabolome of COVID-19 patients is distinctive and has important value in investigating pathogenesis, determining a diagnosis, predicting severe cases, and improving treatment.

Clinical efficacy of methylprednisolone and the combined use of lopinavir/ritonavir with arbidol in treatment of coronavirus disease 2019.

This study aims to comparatively analyze the therapeutic efficacy upon multiple medication plans over lopinavir/ritonavir (LPV/r), arbidol (ARB), and methylprednisolone on patients with coronavirus disease 2019 (COVID-19). Totally, 75 COVID-19 patients admitted to The First Affiliated Hospital, Zhejiang University School of Medicine from January 22, 2020 to February 29, 2020 were recruited and grouped based on whether or not LPV/r and ARB were jointly used and whether or not methylprednisolone was used. Indexes including body temperature, time for nucleic acid negative conversion, hospital stays, and laboratory indexes were examined and compared. For all patients, there were no significant differences in the change of body temperature, the time for negative conversion, and hospital stays whether LPV/r and ARB were jointly used or not. While for severe and critically severe patients, methylprednisolone noticeably reduced the time for negative conversion. Meanwhile, the clinical efficacy was superior on patients receiving methylprednisolone within 3 days upon admission, and the duration of hospital stays was much shorter when methylprednisolone was given at a total dose of 0-400 mg than a higher dose of >400 mg if all patients received a similar dose per day. Nonetheless, no significant changes across hepatic, renal, and myocardial function indexes were observed. LPV/r combined with ARB produced no noticeably better effect on COVID-19 patients relative to the single-agent treatment. Additionally, methylprednisolone was efficient in severe and critically severe cases, and superior efficacy could be realized upon its early, appropriate, and short-term application.

The Artificial-Liver Blood-Purification System Can Effectively Improve Hypercytokinemia for COVID-19.

Since the December 2019 outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, the infection has spread locally and globally resulting in a pandemic. As the numbers of confirmed diagnoses and deaths continue to rise, COVID-19 has become the focus of international public health. COVID-19 is highly contagious, and there is no effective treatment yet. New treatment strategies are urgently needed to improve the treatment success rate of severe and critically ill patients. Increasing evidence has shown that a cytokine storm plays an important role in the progression of COVID-19. The artificial-liver blood-purification system (ALS) is expected to improve the outcome of the cytokine storm. In the present study, the levels of cytokines were detected in 12 COVID-19 patients pre- and post-ALS with promising results. The present study shows promising evidence that ALS can block the cytokine storm, rapidly remove the inflammatory mediators, and hopefully, suppress the progression of the disease, thereby providing a new strategy for the clinical treatment of COVID-19.

Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan. RESULTS: The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13-22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31-8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10-1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11-88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19.

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.

Clinical Characteristics and Factors Associated With Long-Term Viral Excretion in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Single-Center 28-Day Study.

BACKGROUND: Despite the ongoing spread of coronavirus disease 2019 (COVID-19), knowledge about factors affecting prolonged viral excretion is limited. METHODS: In this study, we retrospectively collected data from 99 hospitalized patients with coronavirus disease 2019 (COVID-19) between 19 January and 17 February 2020 in Zhejiang Province, China. We classified them into 2 groups based on whether the virus test results eventually became negative. Cox proportional hazards regression was used to evaluate factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding. RESULTS: Among 99 patients, 61 patients had SARS-CoV-2 clearance (virus-negative group), but 38 patients had sustained positive results (virus-positive group). The median duration of SARS-CoV-2 excretion was 15 (interquartile range, 12-19) days among the virus-negative patients. The shedding time was significantly increased if the fecal SARS-CoV-2 RNA test result was positive. Male sex (hazard ratio [HR], 0.58 [95% confidence interval {CI}, .35-.98]), immunoglobulin use (HR, 0.42 [95% CI, .24-.76]), APACHE II score (HR, 0.89 [95% CI, .84-.96]), and lymphocyte count (HR, 1.81 [95% CI, 1.05-3.1]) were independent factors associated with a prolonged duration of SARS-CoV-2 shedding. Antiviral therapy and corticosteroid treatment were not independent factors. CONCLUSIONS: SARS-CoV-2 RNA clearance time was associated with sex, disease severity, and lymphocyte function. The current antiviral protocol and low-to-moderate dosage of corticosteroid had little effect on the duration of viral excretion.

A COVID-19 case report from asymptomatic contact: implication for contact isolation and incubation management.

BACKGROUND: As of 2 March, 2020, at least 80 151 coronavirus disease 2019 (COVID-19) cases were reported in China. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province or were exposed to symptoms. Some patients got infected through only asymptomatic contact. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection through only asymptomatic contact. CASE PRESENTATION: A 44-year-old man, who lived in Nanchang, Jiangxi Province, China until 6 March 2020, suffered from cough on 27 January 2020. Fever symptoms appeared on 28 January, with a maximum temperature of 38.8 °C, accompanied by cough, sore throat, headache, fatigue, muscle ache, joint ache, and other symptoms. The symptoms continued until he was hospitalized on 30 January. Coronavirus conventional polymerase chain reaction assay was positive for the throat swab sample. The patient, along with his wife and son, drove from Nanchang to back to Honghu City, Hubei Province, on 23 January 2020. After staying with his parents and brother's family for 3 days, the patient drove back to Nanchang and arrived on 25 January. On the way back home, they stopped by Tongshan service area, Hubei Province, without any close contact with other people. After arriving home in Nanchang City, Jiangxi Province, none of them left their residence. In addition, his parents stayed at home for 20 days with his younger brother's family before they got back. His younger brother and one of his brother's children visited Wuhan on 5 January and came home on 6 January 2020. CONCLUSIONS: This report suggested that, in the early phase of COVID-19 pneumonia, routine screening could miss patients who were virus carriers. Highlighting travel history is of paramount importance for the early detection and isolation of severe acute respiratory syndrome coronavirus 2 cases.

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms.

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

A COVID-19 Case Report from Asymptomatic Contact: Implication for Contact Isolation and Incubation Management (preprint)

An outbreak caused by coronavirus disease 2019 (COVID-19) occurred in Wuhan City, Hubei Province, China, in December 2019. Up to March 2, 2020, at least 80180 cases have been reported. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province, or exposed to symptoms. Some patients got infected only from asymptomatic contacts. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection only from asymptomatic contact.