Non-severe Coronavirus Disease 2019 Patients Research Articles

Hydroxychloroquine for treatment of nonsevere COVID-19 patients: Systematic review and meta-analysis of controlled clinical trials.

Being a pandemic and having a high global case fatality rate directed us to assess the evidence strength of hydroxychloroquine efficacy in treating coronavirus disease‐2019 (COVID‐19) arising from clinical trials and to update the practice with the most reliable clinical evidence.A comprehensive search was started in June up to 18 July, 2020 in many databases, including PubMed, Embase, and others. Of 432 studies found, only six studies fulfilled the inclusion criteria, which includes: clinical trials, age more than 12 years with nonsevere COVID‐19, polymerase chain reaction‐confirmed COVID‐19, hydroxychloroquine is the intervention beyond the usual care. Data extraction and bias risk assessment were done by two independent authors. Both fixed‐effect and random‐effect models were utilized for pooling data using risk difference as a summary measure. The primary outcomes are clinical and radiological COVID‐19 progression, severe acute respiratory syndrome coronavirus‐2 clearance in the pharyngeal swab, and mortality. The secondary outcomes are the adverse effects of hydroxychloroquine.Among 609 COVID‐19 confirmed patients obtained from pooling six studies, 294 patients received hydroxychloroquine and 315 patients served as a control. Hydroxychloroquine significantly prevents early radiological progression relative to control with risk difference and 95% confidence interval of −0.2 (−0.36 to −0.03). On the other hand, hydroxychloroquine did not prevent clinical COVID‐19 progression, reduce 5‐day mortality, or enhance viral clearance on days 5, 6, and 7. Moreover, many adverse effects were reported with hydroxychloroquine therapy. Failure of hydroxychloroquine to show viral clearance or clinical benefits with additional adverse effects outweigh its protective effect from radiological progression in nonsevere COVID‐19 patients. Benefit‐risk balance should determine the hydroxychloroquine use in COVID‐19.

Obesity in patients with COVID-19: a systematic review and meta-analysis

BackgroundObesity is common in patients with coronavirus disease 2019 (COVID-19). The effects of obesity on clinical outcomes of COVID-19 warrant systematical investigation. ObjectiveThis study explores the effects of obesity with the risk of severe disease among patients with COVID-19. MethodsBody mass index (BMI) and degree of visceral adipose tissue (VAT) accumulation were used as indicators for obesity status. Publication databases including preprints were searched up to August 10, 2020. Clinical outcomes of severe COVID-19 included hospitalization, a requirement for treatment in an intensive care unit (ICU), invasive mechanical ventilation (IMV), and mortality. Risks for severe COVID-19 outcomes are presented as odds ratios (OR) and 95% confidence interval (95%CI) for cohort studies with BMI-defined obesity, and standardized mean difference (SMD) and 95%CI for controlled studies with VAT-defined excessive adiposity. ResultsA total of 45, 650 participants from 30 studies with BMI-defined obesity and 3 controlled studies with VAT-defined adiposity were included for assessing the risk of severe COVID-19. Univariate analyses showed significantly higher ORs of severe COVID-19 with higher BMI: 1.76 (95%: 1.21, 2.56, P = 0.003) for hospitalization, 1.67 (95%CI: 1.26, 2.21, P<0.001) for ICU admission, 2.19 (95%CI: 1.56, 3.07, P<0.001) for IMV requirement, and 1.37 (95%CI: 1.06, 1.75, P = 0.014) for death, giving an overall OR for severe COVID-19 of 1.67 (95%CI: 1.43, 1.96; P<0.001). Multivariate analyses revealed increased ORs of severe COVID-19 associated with higher BMI: 2.36 (95%CI: 1.37, 4.07, P = 0.002) for hospitalization, 2.32 (95%CI: 1.38, 3.90, P = 0.001) for requiring ICU admission, 2.63 (95%CI: 1.32, 5.25, P = 0.006) for IMV support, and 1.49 (95%CI: 1.20, 1.85, P<0.001) for mortality, giving an overall OR for severe COVID-19 of 2.09 (95%CI: 1.67, 2.62; P<0.001). Compared to non-severe COVID-19 patients, severe COVID-19 cases showed significantly higher VAT accumulation with a SMD of 0.49 for hospitalization (95% CI: 0.11, 0.87; P = 0.011), 0.57 (95% CI: 0.33, 0.81; P<0.001) for requiring ICU admission and 0.37 (95% CI: 0.03, 0.71; P = 0.035) for IMV support. The overall SMD for severe COVID-19 was 0.50 (95% CI: 0.33, 0.68; P<0.001). ConclusionsObesity increases risk for hospitalization, ICU admission, IMV requirement and death among patients with COVID-19. Further, excessive visceral adiposity appears to be associated with severe COVID-19 outcomes. These findings emphasize the need for effective actions by individuals, the public and governments to increase awareness of the risks resulting from obesity and how these are heightened in the current global pandemic.

COVID-19 and Liver Injury: A Systematic Review and Meta-Analysis.

Background and AimsThe prevalence and extent of liver damage in coronavirus disease 2019 (COVID-19) patients remain poorly understood, primarily due to small-sized epidemiological studies with varying definitions of “liver injury”. We conducted a meta-analysis to derive generalizable, well-powered estimates of liver injury prevalence in COVID-19 patients. We also aimed to assess whether liver injury prevalence is significantly greater than the baseline prevalence of chronic liver disease (CLD). Our secondary aim was to study whether the degree of liver injury was associated with the severity of COVID-19.Materials and MethodsElectronic databases (PubMed and Scopus) were systematically searched in June 2020 for studies reporting the prevalence of baseline CLD and current liver injury in hospitalized COVID-19 patients. Liver injury was defined as an elevation in transaminases >3 times above the upper limit of normal. For the secondary analysis, all studies reporting mean liver enzyme levels in severe versus non-severe COVID-19 patients were included. A random-effects model was used for meta-analysis. Proportions were subjected to arcsine transformation and pooled to derive pooled proportions and corresponding 95% confidence intervals (CIs). Subgroup differences were tested for using the chi-square test and associated p-value. Means and their standard errors were pooled to derive weighted mean differences (WMDs) and corresponding 95% CIs.ResultsElectronic search yielded a total of 521 articles. After removal of duplicates and reviewing the full-texts of potential studies, a total of 27 studies met the inclusion criteria. Among a cohort of 8,817 patients, the prevalence of current liver injury was 15.7% (9.5%-23.0%), and this was significantly higher than the proportion of patients with a history of CLD (4.9% [2.2%-8.6%]; p < 0.001). A total of 2,900 patients in our population had severe COVID-19, and 7,184 patients had non-severe COVID-19. Serum ALT (WMD: 7.19 [4.90, 9.48]; p < 0.001; I2 = 69%), AST (WMD: 9.02 [6.89, 11.15]; p < 0.001; I2 = 73%) and bilirubin levels (WMD: 1.78 [0.86, 2.70]; p < 0.001; I2 = 82%) were significantly higher in patients with severe COVID-19 when compared to patients with non-severe disease. Albumin levels were significantly lower in patients with severe COVID-19 (WMD: -4.16 [-5.97, -2.35]; p < 0.001; I2 = 95%).ConclusionsPatients with COVID-19 have a higher than expected prevalence of liver injury, and the extent of the injury is associated with the severity of the disease. Further studies are required to assess whether hepatic damage is caused by the virus, medications, or both.

Immune Phenotyping Based on the Neutrophil-to-Lymphocyte Ratio and IgG Level Predicts Disease Severity and Outcome for Patients With COVID-19.

Introduction: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in COVID-19 patients.Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients at a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared between severe and non-severe patients. Immune response phenotyping based on the late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratified patients into different disease severities and outcomes.Results: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those with low IgG levels (51.8 vs. 32.3%; p = 0.008). Severity rates for patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype were 72.3, 48.5, 33.3, and 15.6%, respectively (p < 0.0001). Furthermore, severe patients with NLRhiIgGhi, NLRhiIgGlo had higher inflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLRloIgGlo phenotype (p < 0.05). Recovery rates for severe patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype were 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p = 0.0592). Dead cases only occurred in NLRhiIgGhi and NLRhiIgGlo phenotypes.Conclusions: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on the late IgG response and NLR could act as a simple complementary tool to discriminate between severe and non-severe COVID-19 patients, and further predict their clinical outcome.

Asymptomatic and Symptomatic Patients With Non-severe Coronavirus Disease (COVID-19) Have Similar Clinical Features and Virological Courses: A Retrospective Single Center Study.

The current outbreak of coronavirus disease 2019 (COVID-19) has been defined as a pandemic by the World Health Organization. We aimed to evaluate the clinical features and virological course of non-severe COVID-19 patients with or without symptoms who were admitted to a Chinese cabin hospital. In this retrospective single center study, we reviewed 252 laboratory-confirmed COVID-19 patients treated at one temporary cabin hospital in Wuhan, China. Demographic, clinical, serial chest computed tomography (CT), and serial viral test data were compared between asymptomatic and symptomatic patients. The association between clinical features and symptomatic status or patient referral status was analyzed. Among all 252 patients, 74 (29.4%) were asymptomatic and 138 (54.76%) had more than two family members who developed COVID-19. The probability for family clustering was similar between asymptomatic and symptomatic patients (59.70 vs. 61.64%, P = 0.79). Asymptomatic patients and symptomatic patients were equally likely to reach a virus-free state during their stay at the cabin hospital (93.15 vs. 86.44%, P = 0.13). The initial chest CT screening showed that 81 (32.1%) patients had no visible pneumonia, 52 (20.6%) had unilateral pneumonia, and 119 (47.2%) had bilateral pneumonia. Symptomatic patients had a higher chance to have bilateral pneumonia (P < 0.0001) and were less likely to show improvement on the follow-up CT scan (P = 0.0002). In total, 69 (27.4%) patients were referred to the designated hospital and only 23 (9.1%) patients were referred due to the progression of pneumonia. Non-severe COVID-19 patients can transmit the disease regardless of their symptomatic status. It is highly recommended that asymptomatic patients be identified and quarantined to eliminate the transmission of COVID-19.

Abnormal Liver Function Tests of Patients with Coronavirus Disease 2019 in Mainland China: A Systematic Review and Meta- Analysis.

Comparing the risk of abnormal liver function tests between severe and non-severe patients with coronavirus disease 2019 (COVID-19) by meta-analysis. A literature search was conducted using the databases PubMed, Embase, and Cochrane Library. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using fixed- or random-effects models. Publication bias was detected by the Harbord test. We included 8 articles comprising 7,467 COVID-19 patients. When compared between severe and non-severe COVID-19 patients, the pooled ORs of elevated alanine aminotransferase, aspartate aminotransferase, total bilirubin, and lactate dehydrogenase levels were 2.35 (95% CI 1.38-3.98), 3.21 (95% CI 2.59-3.98), 1.87 (95% CI 1.32-2.65), and 4.83 (95% CI 2.90-8.05), respectively. The severity of COVID-19 is associated with liver damage, and can be a risk factor for abnormal liver function tests.

Roles of the public-facility-turned temporary hospital in prevention and control of coronavirus disease 2019 in Wuhan, China and clinical experience in the hospital

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, the public-facility-turned temporary hospital (PFTH) has played an important role in preventing the spread of the epidemic. Wuchang PFTH is the first one to put into clinical practice and the last one suspended in Wuhan. The National Emergency Medical Rescue Team of the Second Xiangya Hospital of Central South University, together with other 13 medical teams (841 medical staff in total), have fulfilled the task for the treatment of non-severe COVID-19 patients, without any medical staff infected. The first author of the article was the only pediatrician working in the Wuchang PFTH. The author describes and summarizes the features/functions, management/operations, and advantages/challenges of the PFTH, in order to provide reference for medical institutions and relevant departments to deal with public health emergencies.

C-Reactive Protein Level May Predict the Risk of COVID-19 Aggravation.

BackgroundClinical findings indicated that a fraction of coronavirus disease 2019 (COVID-19) patients diagnosed as mild early may progress to severe cases. However, it is difficult to distinguish these patients in the early stage. The present study aimed to describe the clinical characteristics of these patients, analyze related factors, and explore predictive markers of the disease aggravation.MethodsClinical and laboratory data of nonsevere adult COVID-19 patients in Changsha, China, were collected and analyzed on admission. A logistic regression model was adopted to analyze the association between the disease aggravation and related factors. The receiver operating characteristic curve (ROC) was utilized to analyze the prognostic ability of C-reactive protein (CRP).ResultsAbout 7.7% (16/209) of nonsevere adult COVID-19 patients progressed to severe cases after admission. Compared with nonsevere patients, the aggravated patients had much higher levels of CRP (median [range], 43.8 [12.3–101.9] mg/L vs 12.1 [0.1–91.4] mg/L; P = .000). A regression analysis showed that CRP was significantly associated with aggravation of nonsevere COVID-19 patients, with an area under the curve of 0.844 (95% confidence interval, 0.761–0.926) and an optimal threshold value of 26.9 mg/L.ConclusionsCRP could be a valuable marker to anticipate the possibility of aggravation of nonsevere adult COVID-19 patients, with an optimal threshold value of 26.9 mg/L.

Caution on Kidney Dysfunctions of COVID-19 Patients

Background: To date, large amounts of epidemiological and case study data have been available for the Coronavirus Disease 2019 (COVID-19), which suggested that the mortality was related to not just respiratory complications. Here, we specifically analyzed kidney functions in COVID-19 patients and their relations to mortality. Methods: In this multi-centered, retrospective, observational study, we included 193 adult patients with laboratory-confirmed COVID-19 from 2 hospitals in Wuhan, 1 hospital in Huangshi (Hubei province, 83 km from Wuhan) and 1 hospital in Chongqing (754 km from Wuhan). Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected, including data regarding to kidney functions. Data were compared among three groups: non-severe COVID-19 patients (128), severe COVID-19 patients (65) and a control group of other pneumonia (28). For the data from computed tomographic (CT) scans, we also included a control group of healthy subjects (110 cases, without abnormalities in the lung and without kidney diseases). The primary outcome was a common presence of kidney dysfunctions in COVID-19 patients and the occurrence of acute kidney injury (AKI) in a fraction of COVID-19 patients. Secondary outcomes included a survival analysis of COVID-19 patients in conditions of AKI or comorbid chronic illnesses. Findings: We included 193 COVID-19 patients (128 non-severe, 65 severe (including 32 non-survivors), between January 6th and February 21st ,2020; the final date of follow-up was March 4th, 2020) and 28 patients of other pneumonia (15 of viral pneumonia, 13 of mycoplasma pneumonia) before the COVID-19 outbreak. On hospital admission, a remarkable fraction of patients had signs of kidney dysfunctions, including 59% with proteinuria, 44% with hematuria, 14% with increased levels of blood urea nitrogen, and 10% with increased levels of serum creatinine, although mild but worse than that in cases with other pneumonia. While these kidney dysfunctions might not be readily diagnosed as AKI at admission, over the progress during hospitalization they could be gradually worsened and diagnosed as AKI. A univariate Cox regression analysis showed that proteinuria, hematuria, and elevated levels of blood urea nitrogen, serum creatinine, uric acid as well as D-dimer were significantly associated with the death of COVID-19 patients respectively. Importantly, the Cox regression analysis also suggested that COVID-19 patients that developed AKI had a ~5.3-times mortality risk of those without AKI, much higher than that of comorbid chronic illnesses (~1.5 times risk of those without comorbid chronic illnesses). Interpretation: To prevent fatality in such conditions, we suggested a high degree of caution in monitoring the kidney functions of severe COVID-19 patients regardless of the past disease history. In addition, upon day-by-day monitoring, clinicians should consider any potential interventions to protect kidney functions at the early stage of the disease and renal replacement therapies in severely ill patients, particularly for those with strong inflammatory reactions or a cytokine storm. Funding Statement: This study was supported by grants from the “1000-Talents Program for Young Scholars” of China (X. Chen) and the “100-Talents Program for Elite Engineers” of the CAS (H. Jia). X. Chen is a junior fellow of the CAS Center for Excellence in Brain Science and Intelligence Technology. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study has been approved by the Ethics Commissions of Wuhan Tongji Hospital (TJ-IRB20200216). Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious diseases.

Use of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in COVID-19.

BackgroundAs the pandemic of coronavirus disease 2019 (COVID-19) continues, prognostic markers are now being identified. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are easily accessible values that have been known to correlate with inflammation and prognosis in several conditions. We used the available data to identify the association of NLR and PLR with the severity of COVID-19.MethodsA literature search using EMBASE, MEDLINE, and Google Scholar for studies reporting the use of NLR and PLR in COVID-19 published until April 28, 2020, was performed. Random effects meta-analysis was done to estimate standard mean difference (SMD) of NLR and PLR values with 95% confidence interval (CI) between severe and non-severe COVID-19 cases.ResultsA total of 20 studies with 3,508 patients were included. Nineteen studies reported NLR values, while five studies reported PLR values between severe and non-severe COVID-19 patients. Higher levels of NLR (SMD: 2.80, 95% CI: 2.12 - 3.48, P < 0.00001) and PLR (SMD: 1.82, 95% CI: 1.03 - 2.61, P < 0.00001)) were seen in patients with severe disease compared to non-severe disease.ConclusionsNLR and PLR can be used as independent prognostic markers of disease severity in COVID-19.

Fast Screening and Primary Diagnosis of COVID-19 by ATR FT-IR

Background: The outbreak of coronavirus disease 2019 (COVID-19) has led to substantial infections and mortality around the world. Fast screening and diagnosis are thus crucial to quick isolation and clinical intervention. Methods: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A/B, and respiratory syncytial virus (RSV), as well as healthy controls, were included in this study. All viral infections were confirmed by reverse transcriptase PCR (RT-PCR). The serum samples were measured by attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR). Multivariate and statistical analysis was performed to differentiate between or among groups. Findings: We found that the most discriminatory bands for COVID-19 vs. control classification were amide I, amide II, and νs(PO2−) in original spectra and centered at 1632, 1545, 1400, 1079, and 1037 cm-1 in the second derivative infrared (SD-IR) spectra. Normal controls, non-severe, and severe COVID-19 patients were well separated by unsupervised methods. ATR FT-IR coupled with partial least square discriminant analysis (PLS-DA) was effective to differentiate COVID-19 from normal controls and other respiratory viral infections with the area under the receiver operating characteristic curve (AUROC) of 0·9866 (95%CI 0·9721-0·9939). Interpretation: The band centered at 1633 cm-1 in the SD-IR spectra is mainly attributed to the β-pleated sheet structure from immunoglobulins. Increases in antibody levels and dysregulation of phospholipids can be derived from the measured spectra. The serum FT-IR spectra exhibited “chemical fingerprints” towards different viral infections.Funding Statement: This work was funded by the National Natural Science Foundation of China (52041701).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was approved by the Ethics Committees from TsinghuaUniversity and Peking Union Medical College Hospital.