Behavioral problems of pediatric patients recovered from COVID-19 in Wuhan, China

Background Coronavirus disease 2019 (COVID-19) is profoundly affecting lives around the globe. Previous studies on COVID-19 mainly focused on epidemiological, clinical, and radiological features of patients with confirmed infection. Little attention has been paid to the follow-up of recovered patients. As a vulnerable population to adverse events, the health status of the COVID-19 recovered pediatric patients is of great concern. We aimed to investigate the prevalence of behavioral problems among pediatric patients recovered from the COVID-19 in Wuhan, China. Methods A total of 122 children who were suspected or confirmed COVID-19 cases and hospitalized for treatment were enrolled in the study between April 2020 and May 2020 in Wuhan, China. We collected related information about hospitalization and discharge of the children and emotional symptoms of their parents through electronic medical records and questionnaire. The behavioral problems of children were examined by applying the parent-reported the Strengths and Difficulties Questionnaire (SDQ). Results The participant children were discharged from hospital after about two months. Among them, 76 (62%) were boys, and the mean age was 6.71 years old. The highest prevalence of behavioral problems among pediatric children with COVID-19 was for prosocial behavior (15%), followed by total difficulties (13%), emotional symptoms (11%), hyperactivity (10%), conduct problems (9%), and peer problems (1%). With regarding to their parents, 26% reported having symptoms of anxiety and 23% as having symptoms of depression. The scores of SDQ were higher in those children whose parents have emotional problems compared to parents without. Conclusion Long-term follow up studies on the psychological and behavioral problems of COVID-19 recovered children and their parents are warranted.

Spectrum and Clinical Characteristics of Symptomatic and Asymptomatic Coronavirus Disease 2019 (COVID-19) With and Without Pneumonia (preprint)

BackgroundCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. Based on symptoms, COVID-19 cases can be classified as symptomatic or asymptomatic. However, there is limited information about the differences between COVID-19 patients with and without pneumonia. Our study aimed to further discuss the spectrum and clinical characteristics of symptomatic and asymptomatic COVID-19 patients with and without pneumonia. MethodsIn China, all COVID-19 cases are hospitalized in designated hospitals until two continuous negative oropharyngeal swabs obtained, which allows the professional monitoring of symptoms and clinical characteristics. We stratified all COVID-19 cases in our database, and evaluated clinical characteristics in different COVID-19 subgroups (symptomatic with pneumonia, symptomatic without pneumonia, asymptomatic with pneumonia and asymptomatic without pneumonia). ResultsAccording to symptoms and laboratory and radiologic findings, COVID-19 cases were defined as symptomatic with pneumonia, symptomatic without pneumonia, asymptomatic with pneumonia or asymptomatic without pneumonia. There were differences in the clinical characteristics and prognosis among the four groups. Both noninvasive (18, 4.2%) and invasive mechanical ventilation (11, 2.6%) were applied in only the symptomatic with pneumonia group. Likewise, extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) were applied in only the symptomatic with pneumonia group. There were no differences in the durations of viral shedding and hospitalization among the four groups.ConclusionWe have defined a comprehensive spectrum of COVID-19 with and without pneumonia. The symptomatic with pneumonia group consumed more medical resources than the other groups, and extra caution and monitoring should be applied in this group. The asymptomatic COVID-19 group had a similar viral shedding duration as the symptomatic COVID-19 group.Trial registrationNot available

A Novel Protein Drug, Novaferon, as the Potential Antiviral Drug for COVID-19 (preprint)

Abstract Background Novaferon, a novel protein drug approved for the treatment of chronic hepatitis B in China, exhibits potent antiviral activities. We aimed to determine the anti-SARS-CoV-2 effects of Novaferon in vitro, and conducted a randomized, open-label, parallel group study to explore the antiviral effects of Novaferon for COVID-19. Methods In laboratory, the inhibition of Novaferon on viral replication in cells infected with SARS-CoV-2, and on SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon were evaluated in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir. The primary endpoint was the SARS-CoV-2 clearance rates on day 6 of treatment, and the secondary endpoint was the time to the SARS-CoV-2 clearance in COVID-19 patients Results Novaferon inhibited the viral replication in infected cells (EC50=1.02 ng/ml), and protected healthy cells from SARS-CoV-2 infection (EC50=0.1 ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher SARS-CoV-2 clearance rates on day 6 than the Lopinavir/Ritonavir group (50.0% vs.24.1%, p = 0.0400, and 60.0% vs.24.1%, p = 0.0053). Median time to SARS-CoV-2 clearance were 6 days, 6 days, and 9 days for three groups respectively, suggesting a 3-dayreduction of time to SARS-CoV-2 clearance in both Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with Lopinavir/Ritonavir group. Conclusions Novaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justified the further evaluation of Novaferon. Key words: COVID-19, SARS-CoV-2, Novaferon, Antiviral drug, Lopinavir/Ritonavir

Lymphopenia acted as an adverse factor for severity in patients with COVID-19: a single-centered, retrospective study (preprint)

Purpose: The outbreak of SARS-CoV-2 began in December and rapidly caused a pandemic. To investigate the significance of lymphopenia for the severity of the disease, this study was performed.Methods: 115 patients confirmed COVID-19 from a tertiary hospital in Changsha, China were enrolled. The clinical, laboratory, treatment and outcome data were collected and compared between patients with lymphopenia or not.Results: The median age was 42 years (1-75). 54 patients (47.0%) of the patients had lymphopenia on admission. In the group of lymphopenia, more patients had hypertension (30.8% vs 10.0%, P=0.006) and coronary heart disease (3.6% vs 0%, P=0.029) and more patients with leucopenia (48.1% vs 14.8%, P<0.001) and eosinophilia (92.6% vs 54.1%, P<0.001) were observed. Lymphopenia was also correlated with severity grades of pneumonia (P<0.001) and C-reactive protein (CRP) level (P=0.0014). Lymphopenia was associated with a prolonged duration of hospitalization (17.0 days vs 14.0 days, P=0.002). Moreover, the recovery of lymphocyte appeared the earliest before CRP and chest radiographs in severe cases, suggesting its predictive value for disease improvement. Conclusion: Our results showed the clinical significance of lymphopenia for predicting the severity of COVID-19 and the recovery of the disease, emphasizing the need to monitor the lymphocyte count dynamically.

Epidemiological and clinical features of 291 cases with coronavirus disease 2019 in areas adjacent to Hubei, China: a double-center observational study (preprint)

Abstract Background: The clinical outcomes of COVID-19 patients in Hubei and other areas are different. We aim to investigate the epidemiological and clinical characteristics of patient with COVID-19 in Hunan which is adjacent to Hubei. Methods: In this double-center, observational study, we recruited all consecutive patients with laboratory confirmed COVID-19 from January 23 to February 14, 2020 in two designated hospitals in Hunan province, China. Epidemiological and clinical data from patients' electronic medical records were collected and compared between mild, moderate and severe/critical group in detail. Clinical outcomes were followed up to February 20, 2020. Findings: 291 patients with COVID-19 were categorized into mild group (10.0%), moderate group (72.8%) and severe/critical group (17.2%). The median age of all patients was 46 years (49.8% were male). 86.6% patients had an indirect exposure history. The proportion of patients that had been to Wuhan in severe/critical group (48.0% vs 17.2%, p=0.006) and moderate group (43.4% vs 17.2%, p=0.007) were higher than mild group. Fever (68.7%), cough (60.5%), and fatigue (31.6%) were common symptoms especially for severe and critical patients. Typical lung imaging finding were bilateral and unilateral ground glass opacity or consolidation. Leukopenia, lymphopenia and eosinopenia occurred in 36.1%, 22.7% and 50.2% patients respectively. Increased fibrinogen was detected in 45 of 58 (77.6%) patients with available results. 29 of 44 (65.9%) or 22 of 40 (55.0%) patients were positive in Mycoplasma pneumonia or Chlamydia pneumonia antibody test respectively. Compared with mild or moderate group, severe/critical group had a relative higher level of neutrophil, Neutrophil-to-Lymphocyte Ratio, h-CRP, ESR, CK, CK-MB, LDH, D-dimer, and a lower level of lymphocyte, eosinophils, platelet, HDL and sodium (all p<0.01). Most patients received antiviral therapy and Chinese Medicine therapy. As of February 20, 2020, 159 (54.6%) patients were discharged and 2 (0.7%) patients died during hospitalization. The median length of hospital stay in discharged patients was 12 days (IQR: 10-15). Interpretation: The epidemiological and clinical characteristics of COVID-19 patients in Hunan is different from patients in Wuhan. The proportion of patients that had been to Wuhan in severe/critical group and moderate group were higher than mild group. Laboratory and imaging examination can assist in the diagnosis and classification of COVID-19 patients.