A spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo.

Neutralizing antibodies exert a potent inhibitory effect on viral entry; however, they are less effective in therapeutic models than in prophylactic models, presumably because of their limited efficacy in eliminating virus-producing cells via Fc-mediated cytotoxicity. Herein, we present a SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy for controlling SARS-CoV-2 infection. This approach blocks the entry of free virus into permissive cells by competing with membrane receptors and eliminates virus-infected cells via powerful T cell-mediated cytotoxicity. S-BiTE is effective against both the original and Delta variant of SARS-CoV2 with similar efficacy, suggesting its potential application against immune-escaping variants. In addition, in humanized mouse model with live SARS-COV-2 infection, S-BiTE treated mice showed significantly less viral load than neutralization only treated group. The S-BiTE strategy may have broad applications in combating other coronavirus infections.

Response of PM2.5 pollution to meteorological and anthropogenic emissions changes during COVID-19 lockdown in Hunan Province based on WRF-Chem model.

In December 2019, the New Crown Pneumonia (the COVID-19) outbroke around the globe, and China imposed a nationwide lockdown starting as early as January 23, 2020. This decision has significantly impacted China's air quality, especially the sharp decrease in PM2.5 (aerodynamic equivalent diameter of particulate matter less than or equal to 2.5 µm) pollution. Hunan Province is located in the central and eastern part of China, with a "horseshoe basin" topography. The reduction rate of PM2.5 concentrations in Hunan province during the COVID-19 (24.8%) was significantly higher than the national average (20.3%). Through the analysis of the changing character and pollution sources of haze pollution events in Hunan Province, more scientific countermeasures can be provided for the government. We use the Weather Research and Forecasting with Chemistry (WRF-Chem, V4.0) model to predict and simulate the PM2.5 concentrations under seven scenarios before the lockdown (2020.1.1-2020.1.22) and during the lockdown (2020.1.23-2020.2.14). Then, the PM2.5 concentrations under different conditions is compared to differentiate the contribution of meteorological conditions and local human activities to PM2.5 pollution. The results indicate the most important cause of PM2.5 pollution reduction is anthropogenic emissions from the residential sector, followed by the industrial sector, while the influence of meteorological factors contribute only 0.5% to PM2.5. The explanation is that emission reductions from the residential sector contribute the most to the reduction of seven primary contaminants. Finally, we trace the source and transport path of the air mass in Hunan Province through the Concentration Weight Trajectory Analysis (CWT). We found that the external input of PM2.5 in Hunan Province is mainly from the air mass transported from the northeast, accounting for 28.6%-30.0%. To improve future air quality, there is an urgent need to burn clean energy, improve the industrial structure, rationalize energy use, and strengthen cross-regional air pollution synergy control.

Associations between brain gene expression perturbations implicated by COVID-19 and psychiatric disorders.

BACKGROUND: Currently, there is increasing evidence from clinic, epidemiology, as well as neuroimaging, demonstrating neuropsychiatric abnormalities in COVID-19, however, whether there were associations between brain changes caused by COVID-19 and genetic susceptibility of psychiatric disorders was still unknown. METHODS: In this study, we performed a meta-analysis to investigate these associations by combing single-cell RNA sequencing datasets of brain tissues of COVID-19 and genome-wide association study summary statistics of psychiatric disorders. RESULTS: The analysis demonstrated that among ten psychiatric disorders, gene expression perturbations implicated by COVID-19 in excitatory neurons of choroid plexus were significantly associated with schizophrenia. CONCLUSIONS: Our analysis might provide insights for the underlying mechanism of the psychiatric consequence of COVID-19.

Causes of the unexpected slowness in reducing winter PM2.5 for 2014-2018 in Henan Province.

Toughest-ever clean air actions in China have been implemented nationwide to improve air quality. However, it was unexpected that from 2014 to 2018, the observed wintertime PM2.5 (particulate matter with an aerodynamic diameter of less than 2.5 µm) concentrations showed an insignificant decrease in Henan Province (HNP), a region in the west of the North China Plain. Emission controls seem to have failed to improve winter air quality in HNP, which has caused great confusion in formulating the next air improvement strategy. We employed a deweathering technique to decouple the impact of meteorological conditions. The results showed that the deweathered PM2.5 trend was -3.3%/yr in winter from 2014 to 2018, which had a larger decrease than the observed concentrations (-0.9%/yr), demonstrating that emission reduction was effective at improving air quality. However, compared with the other two megacity clusters, Beijing-Tianjin-Hebei (BTH) (-8.4%/yr) and Yangtze River Delta (YRD) (-7.4%/yr), the deweathered decreasing trend of PM2.5 for HNP remained slow. The underlying mechanism driving the changes in PM2.5 and its chemical components was further explored, using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem). Model simulations indicated that nitrate dominated the increase of PM2.5 components in HNP and the proportions of nitrate to total PM2.5 increased from 22.4% in January 2015 to 39.7% in January 2019. There are two primary reasons for this phenomenon. One is the limited control of nitrogen oxide emissions, which facilitates the conversion of nitric acid to particulate nitrate by ammonia. The other is unfavourable meteorological conditions, particularly increasing humidity, further enhancing nitrate formation through multiphase reactions. This study highly emphasizes the importance of reducing nitrogen oxide emissions owing to their impact on the formation of particulate nitrate in China, especially in the HNP region.

Associations between brain gene expression perturbations implicated by COVID-19 and psychiatric disorders

Background Currently, there is increasing evidence from clinic, epidemiology, as well as neuroimaging, demonstrating neuropsychiatric abnormalities in COVID-19, however, whether there were associations between brain changes caused by COVID-19 and genetic susceptibility of psychiatric disorders was still unknown. Methods In this study, we performed a meta-analysis to investigate these associations by combing single-cell RNA sequencing datasets of brain tissues of COVID-19 and genome-wide association study summary statistics of psychiatric disorders. Results The analysis demonstrated that among ten psychiatric disorders, gene expression perturbations implicated by COVID-19 in excitatory neurons of choroid plexus were significantly associated with schizophrenia. Conclusions Our analysis might provide insights for the underlying mechanism of the psychiatric consequence of COVID-19.

Efficient selective adsorption of cytokine IL-6 and other middle-macromolecular toxins in the serum of uremia patients with specially designed porous hollow carbon spheres

[Display omitted] • Porous hollow carbon spheres (HCSs) with adjustable size and pore width distribution were synthesized. • The clearance rate of HCSs to interleukin 6 (IL-6) in PBS buffer solution was up to 99.8%. • HCSs had a high adsorption rate and removal efficiency for PTH, β 2 -MG, IL-6 and TNF-α in the serum of uremic patients. • The selective adsorption of middle-macromolecular toxins or cytokines was achieved by regulating the pore structure of HCSs. Abnormally elevated middle-macromolecular toxins such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF- α) in human blood are fatal precipitating factors for patients suffered from immune-related diseases, especially for uremia and COVID-19 critical patients, while the effective clearance of them has always been problematic in clinic. In this work, porous hollow carbon spheres (HCSs) with different size and pore structure has been successfully prepared. The removal efficiency for IL-6 in PBS solution is about 99.8 %, even in the serum of uremic patients, HCSs could remove 94.75 % and 98.33 % of parathyroid hormone (PTH) and β 2 -microglobulin (β 2 -MG) efficiently within 5–10 min, and particularly, the adsorption of IL-6 and TNF- α is 17.6 and 11.4 times higher over that of the existing commercial hemoperfusion adsorbents. The adsorption balance can be achieved in 60 min, which would greatly shorten the current clinical treatment duration. Moreover, HCSs with different pore structure exhibit distinct adsorption selectivity for IL-6 and TNF- α, which is of special significance for modifying the middle-macromolecular cytokine level in the complicated human blood environment. [ FROM AUTHOR]

Sex differences in changes of depressive symptoms among older adults before and during the COVID-19 pandemic: evidence from two longitudinal cohorts.

BACKGROUND: Major concerns about the adverse mental health impact of the rapidly spread COVID-19 pandemic have been raised. Previous studies on changes of depressive symptoms during the COVID-19 pandemic have yielded inconsistent results regarding the sex differences. Since women have higher depressive symptoms even without the pandemic, it is essential to consider the pre-existing change of depressive symptoms of a similar period to discern the effect of the pandemic on depression. This study aimed to evaluate sex differences in depressive symptoms before and during the pandemic. METHODS: Data from the Health and Retirement Study (HRS; waves 13 to 15) and the English Longitudinal Study of Ageing (ELSA; wave 8 to COVID-19 wave 2) were analyzed. Depressive symptoms were assessed by the 8-item Center for Epidemiological Studies Depression (CES-D) scale. According to the time of COVID-19 outbreak in the US and the UK, the intervals from waves 13 to 14 surveys of the HRS and from waves 8 to 9 surveys of the ELSA were employed as pre-pandemic periods to control for the pre-existing depressive symptoms, respectively. Changes of CES-D scores during the pre-pandemic and pandemic periods were assessed by linear mixed models. RESULTS: Nine thousand, seven hundred thirty-seven participants (mean age: 66.7 ± 10.7 years) from the HRS and 5,098 participants (mean age: 68.7 ± 10.0 years) from the ELSA were included. CES-D scores among women were significantly higher than those among men at all waves in both cohorts. During the pre-pandemic period, no significant sex difference on changes of CES-D scores was detected in either the HRS or the ELSA. During the pandemic period, CES-D scores were increased in both men and women and the sex differences in CES-D increments of the two cohorts were both significant. Enlarged sex differences were demonstrated in increments of CES-D scores during the pandemic period. CONCLUSIONS: Our results suggest women suffered from worse depressive symptoms in response to the pandemic, although the changes of depression were similar between men and women before the pandemic. These findings underscore the necessity to support the vulnerable populations, especially women, to manage the distress brought by the pandemic and maintain optimal mental health status.

Efficient selective adsorption of cytokine IL-6 and other middle-macromolecular toxins in the serum of uremia patients with specially designed porous hollow carbon spheres

Abnormally elevated middle-macromolecular toxins such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF- α) in human blood are fatal precipitating factors for patients suffered from immune-related diseases, especially for uremia and COVID-19 critical patients, while the effective clearance of them has always been problematic in clinic. In this work, porous hollow carbon spheres (HCSs) with different size and pore structure has been successfully prepared. The removal efficiency for IL-6 in PBS solution is about 99.8%, even in the serum of uremic patients, HCSs could remove 94.75% and 98.33% of parathyroid hormone (PTH) and β2-microglobulin (β2-MG) efficiently within 5-10 min, and particularly, the adsorption of IL-6 and TNF- α is 17.6 and 11.4 times higher over that of the existing commercial hemoperfusion adsorbents. The adsorption balance can be achieved in 60 min, which would greatly shorten the current clinical treatment duration. Moreover, HCSs with different pore structure exhibit distinct adsorption selectivity for IL-6 and TNF- α, which is of special significance for modifying the middle-macromolecular cytokine level in the complicated human blood environment.

Cospeciation of coronavirus and paramyxovirus with their bat hosts in the same geographical areas.

BACKGROUND: Bat-borne viruses are relatively host specific. We hypothesize that this host specificity is due to coevolution of the viruses with their hosts. To test this hypothesis, we investigated the coevolution of coronavirus and paramyxovirus with their bat hosts. Published nucleotide sequences of the RNA-dependent RNA polymerase (RdRp) gene of 60 coronavirus strains identified from 37 bat species, the RNA polymerase large (L) gene of 36 paramyxovirus strains from 29 bat species, and the cytochrome B (cytB) gene of 35 bat species were analyzed for coevolution signals. Each coevolution signal detected was tested and verified by global-fit cophylogenic analysis using software ParaFit, PACo, and eMPRess. RESULTS: Significant coevolution signals were detected in coronaviruses and paramyxoviruses and their bat hosts, and closely related bat hosts were found to carry closely related viruses. CONCLUSIONS: Our results suggest that paramyxovirus and coronavirus coevolve with their hosts.

Engineering mesenchymal stromal cells with neutralizing and anti-inflammatory capability against SARS-CoV-2 infection.

The emergence of the novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the pandemic of coronavirus disease 2019 (COVID-19), which has markedly affected global health and the economy. Both uncontrolled viral replication and a proinflammatory cytokine storm can cause severe tissue damage in patients with COVID-19. SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as its entry receptor. In this study, we generated ACE2 extracellular domain-Fc and single-chain variable fragment-interleukin 6 (IL-6) single-chain variable fragment against IL-6 receptor (scFv-IL6R)-Fc fusion proteins to differentially neutralize viruses and ameliorate the cytokine storm. The human ACE2 (hACE2)1-740-Fc fusion protein showed a potent inhibitory effect on pseudo-typed SARS-CoV-2 entry and a good safety profile in mice. In addition, scFv-IL6R-Fc strongly blocked IL-6 signal activation. We also established a mesenchymal stromal cell (MSC)-based hACE21-740-Fc and scFv-IL6R-Fc delivery system, which could serve as a potential therapy strategy for urgent clinical needs of patients with COVID-19.

Virtual Reality Exposure Therapy (VRET) for Anxiety Due to Fear of COVID-19 Infection: A Case Series.

Virtual reality exposure therapy (VRET) is becoming popular for treating phobia and anxiety disorder. The recent pandemic of COVID-19 not only causes infection per se but also has an impact on mental health. This case series aimed to explore the role of VRET in the intervention of psychiatric illnesses with chief complaints of fear of COVID-19 infection. In vivo exposure therapy for fear of COVID-19 infection is not possible due to the risk of virus infection; in this scenario, the VRET provides an immersive experience and can act as adjunctive therapy for treating phobias and anxiety disorders arising due to novel coronavirus pandemic. Clinical presentation and findings as well as management and procedures of VRET are discussed. Medical record of three patients (two male and one female) at the Shenzhen Mental Health Center (Shenzhen Kangning Hospital), China, was included in the present case series. Patients were assessed with the Hamilton Anxiety Rating Scale and Fear of COVID-19 Scale to measure anxiety and fear, respectively. Throughout VRET sessions, we gradually and systematically exposed the patient to virtual COVID-19 scenarios (for example, touching stained door handle which may have viruses, watching pandemic news, watching frontline health care workers, etc.). In our study, VRET intervention significantly reduced the related symptoms caused by fear of COVID-19 infection. Furthermore, virtual reality can provide relevant theoretical and practical support for exploring the remote psychological counseling of patients in isolation wards.

[Mental health status and its influencing factors among general population and medical personnel in Guangdong Province during COVID-19 pandemic].

OBJECTIVE: To investigate the mental health status and its influencing factors among general population and healthcare professionals in Guangdong Province during COVID-19 pandemic. METHODS: A online questionnaire-based survey was conducted from March 11st to March 15th, 2020.The questionnaire consisted of 4 parts to survey the participants'basic information, understanding of COVID-19 outbreak-associated information, cognition of COVID-19 pandemic and status of anxiety and depression.A total of 1433 valid responses were collected, including 706 from the general population and 727 from healthcare professionals.Cronbach's α coefficient and exploratory factor analysis were used for reliability and validity assessment.Chi-square, Wilcoxon and Kruskal-Wallis test were used for univariate analysis and ordinal or nominal logistic regression was used for multivariate analysis of the data. RESULTS: There was no significant difference between the general population and the healthcare professionals in terms of anxiety, depression and cognition of COVID-19 outbreak after adjustment for demographic variables, but the levels of anxiety and depression of these participants were both higher than those before the pandemic.In the participants from the general population, multivariate logistic regressions showed an OR for anxiety of 1.93(1.18, 3.17) among those who spent 1-2 h a day in reading COVID-19-related news, while those who spent over 3 h had an OR value for anxiety of 1.88(1.14, 3.11);the unmarried individuals had a depression OR of 2.19(1.51, 3.18). Inaccurate cognition of COVID-19 outbreak was positive correlated with the occurrence of anxiety and depression.Unmarried individuals and those with higher educational levels had better cognition of COVID-19 outbreak.Among the healthcare professionals, multivariate logistic regressions suggested that insufficient rest time and worries about contracting the virus contributed to the occurrence of anxiety and depression.Among the nursing staff, the OR of obvious depression was 2.99(1.45, 6.18).Compared to healthcare professionals not working in designated hospital for COVID-19, those who work in the designated hospitals had ORs for obvious and severe depression of 0.48(0.25, 0.93) and 0.39(0.17, 0.89), respectively.Concerns over contracting the virus increased the possibility of incorrect cognition of COVID-19. CONCLUSIONS: Psychological interventions are essential for both the general population and healthcare professionals, especially for unmarried individuals in the general population and the nursing staff.An excessive exposure to COVID-19-related information may have detrimental effects on the mental health.For healthcare professionals, sufficient rest needs to be ensured, and education programs on COVID-19 should be implemented among both residents and healthcare professionals to improve their mental health.

Digestive symptoms and liver injury in patients with coronavirus disease 2019 (COVID-19): A systematic review with meta-analysis.

Although most COVID-19 patients typically present with respiratory symptoms, many patients could experience digestive symptoms as the major complaint. We performed a systematic review and meta-analysis to investigate the exact prevalence of digestive symptoms and liver injury in COVID-19 patients and compare the difference between patients with and without digestive symptoms. PubMed, Embase, Ovid, Wanfang data, and CNKI were searched until 24 April 2020 to identify studies that reported digestive symptoms and liver injury in COVID-19 patients. A random-effect model was used to combine the data. Finally, 64 studies with 15 141 patients were included. The pooled rate of digestive symptoms and liver dysfunction was 31.8% (95 CI 21.0-42.5%, I 2 = 97.6%) and 27.4% (95 CI 16.9-37.9%, I 2 = 97.9%), respectively. Patients with digestive symptoms were more likely to present with fatigue (OR 2.28, 95 CI 1.66-3.14, P < 0.00001, I 2 = 31%), myalgia (OR 1.96, 95 CI 1.06-3.65, P = 0.03, I 2 = 69%), and acute respiratory disease syndrome (ARDS) (OR 2.94, 95 CI 1.17-7.40, P = 0.02, I 2 = 0) and had a trend to present as severe/critical type (OR 1.87, 95 CI 0.98-3.57, P = 0.06, I 2 = 58%). Severe/critical patients were more likely to present with diarrhea (OR 2.02, 95 CI 1.16-3.50, P = 0.01, I 2 = 64) and have high alanine aminotransferase (ALT) (OR 2.08, 95 CI 1.55-2.81, P < 0.00001, I 2 = 13%,) and aspartate aminotransferase (AST) (OR 3.53, 95 CI 2.76-4.51, P < 0.00001, I 2 = 0). The pooled rate of patients with digestive symptoms was 28.7% (95 CI 17.6-39.8%) and 42.8% (95 CI 23.4-62.3%) in studies from China and out of China, respectively. COVID-19 patients had a high rate of digestive symptoms and liver injury. Patients with digestive symptoms had a trend to develop severe/critical illness.

Involvement of digestive system in COVID-19: manifestations, pathology, management and challenges.

The pandemic of novel coronavirus disease (COVID-19) has developed as a tremendous threat to global health. Although most COVID-19 patients present with respiratory symptoms, some present with gastrointestinal (GI) symptoms like diarrhoea, loss of appetite, nausea/vomiting and abdominal pain as the major complaints. These features may be attributable to the following facts: (a) COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in GI epithelial cells, providing a prerequisite for SARS-CoV-2 infection; (b) SARS-CoV-2 viral RNA has been found in stool specimens of infected patients, and 20% of patients showed prolonged presence of SARS-CoV-2 RNA in faecal samples after the virus converting to negative in the respiratory system. These findings suggest that SARS-CoV-2 may be able to actively infect and replicate in the GI tract. Moreover, GI infection could be the first manifestation antedating respiratory symptoms; patients suffering only digestive symptoms but no respiratory symptoms as clinical manifestation have also been reported. Thus, the implications of digestive symptoms in patients with COVID-19 is of great importance. In this review, we summarise recent findings on the epidemiology of GI tract involvement, potential mechanisms of faecal-oral transmission, GI and liver manifestation, pathological/histological features in patients with COVID-19 and the diagnosis, management of patients with pre-existing GI and liver diseases as well as precautions for preventing SARS-CoV-2 infection during GI endoscopy procedures.

Clinical course and treatment efficacy of COVID-19 near Hubei Province, China: A multicentre, retrospective study.

Currently, COVID-19 has been reported in nearly all countries globally. To date, little is known about the viral shedding duration, clinical course and treatment efficacy of COVID-19 near Hubei Province, China. This multicentre, retrospective study was performed in 12 hospitals in Henan and Shaanxi Provinces from 20 January to 8 February 2020. Clinical outcomes were followed up until 26 March 2020. The viral shedding duration, full clinical course and treatment efficacy were analysed in different subgroups of patients. A total of 149 COVID-19 patients were enrolled. The median age was 42 years, and 61.1% (91) were males. Of them, 133 (89.3%) had fever, 131 of 144 (91%) had pneumonia, 27 (18.1%) required intensive care unit (ICU) management, 3 (2%) were pregnant, and 3 (2%) died. Two premature newborns were negative for SARS-CoV-2. In total, the median SARS-CoV-2 shedding period and clinical course were 12 (IQR: 9-17; mean: 13.4, 95% CI: 12.5, 14.2) and 20 (IQR: 16-24; mean: 21.2, 95% CI: 20.1, 22.3) days, respectively, and ICU patients had longer median viral shedding periods (21 [17-24] versus 11 [9-15]) and clinical courses (30 [22-33] vs. 19 [15.8-22]) than non-ICU patients (both p < .0001). SARS-CoV-2 clearances occurred at least 2 days before fatality in 3 non-survivors. Current treatment with any anti-viral agent or combination did not present the benefit of shortening viral shedding period and clinical course (all p > .05) in real-life settings. In conclusion, the viral shedding duration and clinical course in Henan and Shaanxi Provinces were shorter than those in Hubei Province, and current anti-viral therapies were ineffective for shortening viral shedding duration and clinical course in real-world settings. These findings expand our knowledge of the SARS-CoV-2 infection and may be helpful for management of the epidemic outbreak of COVID-19 worldwide. Further studies concerning effective anti-viral agents and vaccines are urgently needed.

Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates. FINDINGS: We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2-5; range 0-15; I2=74%). The pooled prevalence of digestive symptoms was 15% (10-21; range: 2-57; I2=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9-32; range 1-53; I2=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of abdominal pain (odds ratio [OR] 7·10 [95% CI 1·93-26·07]; p=0·003; I2=0%) and abnormal liver function including increased ALT (1·89 [1·30-2·76]; p=0·0009; I2=10%) and increased AST (3·08 [2·14-4·42]; p<0·00001; I2=0%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4-19; range 3-23; I2=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 [95% CI 0·22-5·48]; p=0·030; I2=73%). Patients with gastrointestinal involvement tended to have a poorer disease course (eg, acute respiratory distress syndrome OR 2·96 [95% CI 1·17-7·48]; p=0·02; I2=0%). INTERPRETATION: Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients. FUNDING: None.