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.

Predictors of COVID-19 Infection: A Prevalence Study of Hospitalized Patients.

AIM: To find the predictors of coronavirus disease 2019 (COVID-19) in hospitalized patients. METHODS: A prevalence study compared the characteristics of COVID-19 patients with non-COVID-19 patients from January 19, 2020, to February 18, 2020, during the COVID-19 outbreak. Laboratory test results and pulmonary chest imaging of confirmed COVID-19 and non-COVID-19 patients were collected by retrieving medical records in our center. RESULTS: 96 COVID-19 patients and 122 non-COVID-19 patients were enrolled in this study. COVID-19 patients were older (53 vs. 39; P < 0.001) and had higher body mass index (BMI) than non-COVID-19 group (24.21 ± 3.51 vs. 23.00 ± 3.27, P = 0.011); however, differences in gender were not observed between the two groups. Logistic regression analysis showed that exposure history (OR: 23.34, P < 0.001), rhinorrhea (odds radio (OR): 0.12, P = 0.006), alanine aminotransferase (ALT) (OR: 1.03, P = 0.049), lactate dehydrogenase (LDH) (OR: 1.01, P = 0.020), lymphocyte (OR: 0.27, P = 0.007), and bilateral involvement on chest CT imaging (OR: 23.01, P < 0.001) were independent risk factors for COVID-19. Moreover, bilateral involvement on chest CT imaging (AUC = 0.904, P < 0.001) had significantly higher AUC than others in predicting COVID-19. CONCLUSIONS: Exposure history, elevated ALT and LDH, absence of rhinorrhea, lymphopenia, and bilateral involvement on chest CT imaging provide robust evidence for the diagnosis of COVID-19, especially in resource-limited conditions where nucleic acid detection is not readily available.

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.

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 Clinical and Radiological Manifestations in Coronavirus Disease 2019 With Negative Nucleic Acid Results.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was a new emerging disease with high infectiousness. Its diagnosis primarily depended on real-time polymerase chain reaction (RT-PCR) results. This study investigated epidemiological, clinical, and radiological characteristics of COVID-19 with negative RT-PCR results before confirmation. METHODS: Patients with COVID-19 were enrolled and divided into 2 groups: a negative group with negative RT-PCR results before confirmation and a positive group with positive results at the first detection. Epidemiological and clinical features were compared. Dynamic chest computerized tomography (CT) images of the negative group were evaluated. RESULTS: Ninety-nine laboratory-confirmed patients with COVID-19 including 8 patients (8%) with negative RT-PCR results were included. Patients from the negative group had similar epidemiological features: the average age (50.25 ±â€…13.27 years in the negative group and 53.70 ±â€…16.64 years in the positive group) and gender distribution (males made up 50% of the negative group and 62.6% of the positive group) were comparable. No significant differences were observed in clinical symptoms between the 2 groups. We found that fever was the most common symptom for both groups, followed by cough, expectoration, chest distress, fatigue, and gastroenterological symptoms. Moreover, ground-glass opacities and consolidations were the main manifestation in chest CT of patients with COVID-19 with or without confirmed RT-PCR results. CONCLUSIONS: Regardless of initial RT-PCR results, patients with COVID-19 had similar epidemiological, clinical, and chest CT features. Our study suggests value from early chest CT scans in COVID-19 screening and dynamic significance of radiology in disease monitoring should guide clinical decisions.

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.

Erratum to: Transmission risk of patients with COVID-19 meeting discharge criteria should be interpreted with caution.

Erratum to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2020 21(5):408-410. https://doi.org/10.1631/jzus.B2000117. The original version of this article unfortunately contained a mistake. For Fig. 1a in p.409, the citation of a reference, as well as the permission to reprint this picture, was missing. The correct version and the corresponding reference are given below: (a) Chest computed tomography (CT) image of Patient 1 on admission presents multiple ground-glass opacities distributed in the periphery of inferior lobe of both lungs. Reprinted from Zhang et al. (2020), with kind permission from Springer Nature.

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.