A burns and COVID-19 shared stress responding gene network deciphers CD1C-CD141- DCs as the key cellular components in septic prognosis (preprint)

Differential body responses to various stresses, infectious or noninfectious, govern clinical outcomes ranging from asymptoma to death. However, the common molecular and cellular nature of the stress responsome across different stimuli is not described. In this study, we compared the expression behaviors between burns and COVID-19 infection by choosing the transcriptome of peripheral blood from related patients as the analytic target since the blood cells reflect the systemic landscape of immune homeostasis. We identified an immune co-stimulator (CD86)-centered network, named stress-response core (SRC), which coordinated multiple immune processes and was robust in membership and highly related to the clinical traits in both burns and COVID-19. An independent whole blood single-cell RNA sequencing of COVID-19 patients demonstrated that the monocyte-dendritic cell (Mono-DC) wing was the major cellular source of the SRC, among which the higher expression of the SRC in the monocyte was associated with the asymptomatic COVID-19 patients, while the quantity-restricted and function-defected CD1C-CD141- DCs were recognized as the key signature which linked to bad consequences in COVID-19. Specifically, the proportion of the CD1C-CD141- DCs and their SRC expression levels were step-wise reduced along with worse clinic conditions while the sub-cluster of CD1C-CD141- DCs of the critical COVID-19 patients was characterized of IFN signaling quiescence, high mitochondrial metabolism and immune-communication inactivation. Thus, our study identified an expression-synchronized and function-focused gene network which was decreased under burns and COVID-19 stress and argued the CD1C-CD141- DC as the prognosis-related cell population which might serve as a new target of diagnosis and therapy.

COVID-19 instigates adipose browning and atrophy through VEGF in small mammals.

Patients with COVID-19 frequently manifest adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality1,2. Browning of white adipose tissue and activation of brown adipose tissue are effective processes for energy expenditure3-7; however, mechanistic and functional links between SARS-CoV-2 infection and adipose thermogenesis have not been studied. In this study, we provide experimental evidence that SARS-CoV-2 infection augments adipose browning and non-shivering thermogenesis (NST), which contributes to adipose atrophy and body weight loss. In mouse and hamster models, SARS-CoV-2 infection activates brown adipose tissue and instigates a browning or beige phenotype of white adipose tissues, including augmented NST. This browning phenotype was also observed in post-mortem adipose tissue of four patients who died of COVID-19. Mechanistically, high levels of vascular endothelial growth factor (VEGF) in the adipose tissue induces adipose browning through vasculature-adipocyte interaction. Inhibition of VEGF blocks COVID-19-induced adipose tissue browning and NST and partially prevents infection-induced body weight loss. Our data suggest that the browning of adipose tissues induced by COVID-19 can contribute to adipose tissue atrophy and weight loss observed during infection. Inhibition of VEGF signaling may represent an effective approach for preventing and treating COVID-19-associated weight loss.

Using search trends before and after the COVID-19 outbreak in China to analyze digestive symptoms: medical informatics study of the Baidu Index data

Background From the beginning of 2020, the world was plunged into a pandemic caused by the novel coronavirus disease-19 (COVID-19). People increasingly searched for information related to COVID-19 on internet websites. The Baidu Index is a data sharing platform. The main data provided is the search index (SI), which represents the frequency that keywords are used in searches. Methods January 9, 2020 is an important date for the outbreak of COVID-19 in China. We compared the changes of SI before and after for 7 keywords, including “fever”, “cough”, “nausea”, “vomiting”, “abdominal pain”, “diarrhea”, “constipation”. The slope and peak values of SI change curves are compared. Ten provinces in China were selected for a separate analysis, including Beijing, Gansu, Guangdong, Guangxi, Heilongjiang, Hubei, Sichuan, Shanghai, Xinjiang, Tibet. The change of SI was analyzed separately, and the correlation between SI and demographic and economic data was analyzed. Results During period I, from January 9 to January 25, 2020, the average daily increase (ADI) of the SI for “diarrhea” was lower than that for “cough” (889.47 vs. 1,799.12, F=11.43, P=0.002). In period II, from January 25 to April 8, 2020, the average daily decrease (ADD) of the SI for “diarrhea” was significantly lower than that for “cough”, with statistical significance (cough, 191.40 vs. 441.44, F=68.66, P<0.001). The mean SI after January 9, 2020 (pre-SI) was lower than that before January 9, 2020 (post-SI) (fever, 2,616.41±116.92 vs. 3,724.51±867.81, P<0.001;cough, 3,260.04±308.43 vs. 5,590.66±874.25, P<0.001;diarrhea, 4,128.80±200.82 vs. 4,423.55±1,058.01, P<0.001). The pre-SI mean was correlated with population (P=0.004, R=0.813) and gross domestic product (GDP) (P<0.001, R=0.966). The post-SI peak was correlated with population (P=0.007, R=0.789), GDP (P=0.005, R=0.804), and previously confirmed cases (PCC) (P=0.03, R=0.670). The growth rate of the SI was correlated with the post-SI peak (P=0.04, R=0.649), PCC (P=0.003, R=0.835). Conclusions Diarrhea was of widespread concern in all provinces before and after the COVID-19 outbreak and may be associated with novel coronavirus infection. Internet big data can reflect the public’s concern about diseases, which is of great significance for the study of the epidemiological characteristics of diseases.

Immunogenicity and protective potential of chimeric virus-like particles containing SARS-CoV-2 spike and H5N1 matrix 1 proteins

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has posed a constant threat to human beings and the world economy for more than two years. Vaccination is the first choice to control and prevent the pandemic. However, an effective SARS-CoV-2 vaccine against the virus infection is still needed. This study designed and prepared four kinds of virus-like particles (VLPs) using an insect expression system. Two constructs encoded wild-type SARS-CoV-2 spike (S) fused with or without H5N1 matrix 1 (M1) (S and SM). The other two constructs contained a codon-optimized spike gene and/or M1 gene (mS and mSM) based on protein expression, stability, and ADE avoidance. The results showed that the VLP-based vaccine could induce high SARS-CoV-2 specific antibodies in mice, including specific IgG, IgG1, and IgG2a. Moreover, the mSM group has the most robust ability to stimulate humoral immunity and cellular immunity than the other VLPs, suggesting the mSM is the best immunogen. Further studies showed that the mSM combined with Al/CpG adjuvant could stimulate animals to produce sustained high-level antibodies and establish an effective protective barrier to protect mice from challenges with mouse-adapted strain. The vaccine based on mSM and Al/CpG adjuvant is a promising candidate vaccine to prevent the COVID-19 pandemic.

Investigation of the mechanism of fangfeng tongsheng pills in the treatment COVID-19 by network pharmacology and molecular docking

Objective: To explore the active components and potential mechanism of Fangfeng Tongsheng Pills by using network pharmacology and molecular docking in the treatment of coronavirus disease 19(COVID-19). Methods The main chemical constituents and action targets of various medicines in Fangfeng Tongsheng Pills were collected via traditional Chinese medicine system pharmacology database and online analysis platform(TCMSP). The related targets of COVID-19 were collected by using GeneCards database, and the repeating parts with Fangfeng Tongsheng Pills were taken as the research targets. Cytoscape software was used to create a drug-target-disease network. The common target was imported into STRING database, and the protein-protein interaction network diagram was constructed by Cytoscape software. The GO(gene ontology) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed by DAVID to predict their mechanism. The core components of Fangfeng Tongsheng Pills were docked with the therapeutic target of COVID-19 by AutoDock software. Results A total of 224 active compounds and 696 active targets were screened from Fangfeng Tongsheng Pills, including 79 targets coincided with COVID-19, and 10 active compounds, i.e. quercetin, luteolin, kaempferol,beta-sitosterol, naringenin, etc., 23 effective targets, i.e. PTGS2, PTGS1, NOS2, F10, DPP4, etc. A total of 65 GO function enrichment analysis results and 101 KEGG pathway enrichment results were obtained, including inflammatory response, tumor necrosis factor(TNF) signaling pathway, hypoxia inducible factor-1(HIF-1) signaling pathway, vascular endothelial growth factors(VEGF) signaling pathway, toll-like receptors(TLRs) signaling pathway, phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt) signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. Conclusion The active components in Fangfeng Tongsheng Pills, such as beta-sitosterol, quercetin, luteolin, kaempferol and naringenin, can combine with SARS-Co V2-3CL hydrolase and ACE2, act on the key target [TNF, Caspase-3, mitogen-activated protein kinase(MAPK1), interleukin-6(IL-6), prostaglandin-endoperoxide synthase 2(PGTS2)] of TNF, HIF-1, VEGF, MAPK and toll-like receptor signaling pathway, and play the roles of anti-inflammation, immune regulation, anti-hypoxic stress and anti-virus infection, thus play a role in the treatment of COVID-19.

How do Facilitating Conditions Influence Student-to-Student Interaction within an Online Learning Platform? A New Typology of the Serial Mediation Model

This study investigates factors affecting university student-to-student interaction within online learning platforms. A new model was proposed based on the United Theory of Acceptance and Use of Technology (UTAUT). The single-stage cluster-sampling method was employed, and 113 university students in Hong Kong were respondents. It was found that Information Quality, Social Influence, and Facilitating Conditions affect students’ intention to interact with each other. A quasi-full mediation model was established of the mechanism from Facilitating Conditions to students’ interaction behavior. The direct effect of Facilitating Conditions on students’ interaction and the effect of System Quality on the intention of student interaction were not significant. A fast network, computing facilities, and mobile-friendly software are possible candidates of the virtual environment conditions affecting the intention of student-interaction behavior within online learning platforms.

Satisfaction and Demands of Indoor Space in the High-Density Residential Areas in the COVID-19 Era

The last few years have witnessed a change in residents' demand for indoor space due to the COVID-19 pandemic. From the perspective of residential satisfaction in the urban areas in various levels of COVID-19 severity, the household survey was conducted to explore the changing residential demands. The IBM SPSS Statistics was employed to analyze the survey data with a focus on the relationship between pandemic severity and residents' satisfaction, as well as the future influence of COVID-19 on indoor space and the varying demands. Correlation analysis was performed. The variables included in the correlation analysis were the following: urban epidemic severity, number of confirmed cases, density of confirmed cases, regional pandemic severity and satisfaction of different indoor spaces. This study revealed that the hallway, bathroom, living room and master bedroom are key areas in which the residential demands are concentrated. These should be paid attention to in the future residential design.

Effects of First-Time Experiences and Self-Regulation on College Students' Online Learning Motivation: Based on a National Survey during COVID-19

The COVID-19 pandemic has forced many college students in developing countries to engage in online learning for the first time, and the sudden transit has raised concerns regarding students' competencies for, perception of, and attitude towards online learning. To address those concerns, this study measured three essential constructs of online learning (self-regulated learning, perceived presences, and learning motivation) based on a national survey in China (N = 12,826) and employed structural equation modeling to investigate their intertwined relationship. The study results reveal that (1) college students' academic achievement cannot effectively predict their self-regulated learning in an online learning context;(2) self-regulation can be further differentiated into general and task-specific strategies with a varying impact on three types of presences;(3) online learning motivation is best predicted by cognitive presence, followed by social presence and teaching presence;and (4) the path of task-specific self-regulated learning →cognitive presence →online learning motivation generates the largest positive compound effect. Implications for online teaching and learning practice are also discussed through the stakeholder perspectives of students, teachers, and platform developers.

Human Brain Organoids as an In Vitro Model System of Viral Infectious Diseases

Brain organoids, or brainoids, have shown great promise in the study of central nervous system (CNS) infection. Modeling Zika virus (ZIKV) infection in brain organoids may help elucidate the relationship between ZIKV infection and microcephaly. Brain organoids have been used to study the pathogenesis of SARS-CoV-2, human immunodeficiency virus (HIV), HSV-1, and other viral infections of the CNS. In this review, we summarize the advances in the development of viral infection models in brain organoids and their potential application for exploring mechanisms of viral infections of the CNS and in new drug development. The existing limitations are further discussed and the prospects for the development and application of brain organs are prospected.

Performance of COVIDSeq and Swift normalase amplicon SARS-CoV-2 panels for SARS-CoV-2 Genomes Sequencing: Practical Guide and Combining FASTQ Strategy (preprint)

The whole genomic sequencing (WGS) of SARS-CoV-2 has been performed extensively and is playing a crucial role in fighting against COVID-19 pandemic. Obtaining sufficient WGS data from clinical samples is often challenging especially from the samples with low viral load. We evaluated two SARS-CoV-2 sequencing protocols for their efficiency/accuracy and limitations. Sequence coverage of >95% was obtained by Swift normalase amplicon SARS-CoV-2 panels (SNAP) protocol for all the samples with Ct [≤] 35 and by COVIDSeq protocol for 97% of samples with Ct [≤] 30. Sample RNA quantitation obtained using digital PCR provided more precise cutoff values. The quantitative digital PCR cutoff values for obtaining 95% coverage are 10.5 copies/L for SNAP protocol and 147 copies/L for COVIDSeq protocol. Combining FASTQ files obtained from 2 protocols improved the outcome of sequence analysis by compensating for missing amplicon regions. This process resulted in an increase of sequencing coverage and lineage call precision.

Investigation on Residents Exercise Behavior Situation during the Novel Coronavirus Pneumonia

Abstract: Objective: To know the effect of novel coronavirus pneumonia (NCP) on residents exercise behavior and provide reference for resident when exercising at home during isolation. Methods: Taking WeChat as the media for distributing questionnaires and using self-designed questionnaires, we investigated the situation of residents exercise behavior during NCP and compared with the situation before NCP. Results: The research investigated 468 residents totally (aging from 18-71). During the NCP, the proportion of residents participating in exercise decreased significantly (88.4％ vs. 73.9％, P < 0.05). The exercise time changed from 30-60 min / time before the NCP to < 30 min / time;during the NCP, the main purpose of exercise was to improve immunity and prevent diseases, and the place of exercise was still courtyard or indoor, but the proportion increased by 4.9％ and 23.4％ respectively (P < 0.05);the main obstacle factors were self inertia (21.1％) and lack of time (12.0％). Conclusion: To a certain extent, home isolation has changed the exercise behavior of residents, including exercise mode, frequency, intensity and location.

Depression, Anxiety, and Suicidal Ideation in Chinese University Students During the COVID-19 Pandemic.

Coronavirus disease-2019 (COVID-19) pandemic has seriously threatened the global public health security and caused a series of mental health problem. Current research focuses mainly on mental health status and related factors in the COVID-19 pandemic among Chinese university students. Data from 11133 participants was obtained through an online survey. The Patient Health Question-9 (PHQ-9) was used to assess depressive symptoms, the Social Support Rate Scale (SSRS) was used to assess social support. We also used 7-item Generalized Anxiety Disorder Scale (GAD-7) to assess anxiety symptoms. Totally, 37.0% of the subjects were experiencing depressive symptoms, 24.9% anxiety symptoms, 20.9% comorbid depressive and anxiety symptoms, and 7.3% suicidal ideation. Multivariable logistic regression analysis revealed an increased presence of mental health problems in female students, graduate students, and those with personal COVID-19 exposure. Awareness of COVID-19, living with family were protective factors that reduced anxiety and depression symptoms. In addition, male, personal COVID-19 exposure, depressive and anxiety symptoms were risk factors for suicidal ideation. Social support, COVID-19 preventive and control measures, prediction of COVID-19 trends, living with family and graduate students are protective factors for reducing suicidal ideation.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant (preprint)

We report the first local transmission of the SARS-CoV-2 Delta variant in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of the quarantined subjects indicated that the viral loads of Delta infections, when they first become PCR+, were on average ~1000 times greater compared to A/B lineage infections during initial epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. We performed high-quality sequencing on samples from 126 individuals. Reliable epidemiological data meant that, for 111 transmission events, the donor and recipient cases were known. The estimated transmission bottleneck size was 1-3 virions with most minor intra-host single nucleotide variants (iSNVs) failing to transmit to the recipients. However, transmission heterogeneity of SARS-CoV-2 was also observed. The transmission of minor iSNVs resulted in at least 4 of the 30 substitutions identified in the outbreak, highlighting the contribution of intra-host variants to population level viral diversity during rapid spread. Disease control activities, such as the frequency of population testing, quarantine during pre-symptomatic infection, and level of virus genomic surveillance should be adjusted in order to account for the increasing prevalence of the Delta variant worldwide.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant (preprint)

Summary We report the first local transmission of the SARS-CoV-2 Delta variant in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of the quarantined subjects indicated that the viral loads of Delta infections, when they first become PCR+, were on average ∼1000 times greater compared to A/B lineage infections during initial epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. We performed high-quality sequencing on samples from 126 individuals. Reliable epidemiological data meant that, for 111 transmission events, the donor and recipient cases were known. The estimated transmission bottleneck size was 1-3 virions with most minor intra-host single nucleotide variants (iSNVs) failing to transmit to the recipients. However, transmission heterogeneity of SARS-CoV-2 was also observed. The transmission of minor iSNVs resulted in at least 4 of the 30 substitutions identified in the outbreak, highlighting the contribution of intra-host variants to population level viral diversity during rapid spread. Disease control activities, such as the frequency of population testing, quarantine during pre-symptomatic infection, and level of virus genomic surveillance should be adjusted in order to account for the increasing prevalence of the Delta variant worldwide.

Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of COVID-19 death.

Most COVID-19 victims are old and die from unrelated causes. Here we present twelve complete autopsies, including two rapid autopsies of young patients where the cause of death was COVID-19 ARDS. The main virus induced pathology was in the lung parenchyma and not in the airways. Most coagulation events occurred in the intra-alveolar and not in the intra-vascular space and the few thrombi were mainly composed of aggregated thrombocytes. The dominant inflammatory response was the massive accumulation of CD163 + macrophages and the disappearance of T killer, NK and B-cells. The virus was replicating in the pneumocytes and macrophages but not in bronchial epithelium, endothelium, pericytes or stromal cells. The lung consolidations were produced by a massive regenerative response, stromal and epithelial proliferation and neovascularization. We suggest that thrombocyte aggregation inhibition, angiogenesis inhibition and general proliferation inhibition may have a roll in the treatment of advanced COVID-19 ARDS.

Survival potential and infectiousness of SARS-CoV-2 in environment

Coronavirus disease 2019 (COVID-19) spreads rapidly and widely in the world, which is mainly transmitted through respiratory droplets and contact with contaminated media. In this study, SARS-CoV-2 was found to have a similar stability to severe acute respiratory syndrome coronavirus (SARS-CoV) by analyzing its survival time on different subject surfaces and main influencing factors in related research. SARS-CoV-2 can survive for several days at various subject surfaces or media at room temperature (stainless steel: 2 days, plastic: 3 days, glass: 4 days, etc.), and SARS-CoV-2 can persist for longer time at low temperature and low relative humidity, which has caused severe threat to public health and has posed severe challenges to the prevention and control of COVID-19. According to available data, SARS-CoV-2 has the characteristics of high infectiousness and high covertness, similar to influenza A virus. By understanding the survival potential and infectiousness of SARS-CoV-2 in environment, targeted disinfection and effective protection can be implemented to reduce the incidence of COVID-19.

Clinical evaluation of the Abbott Alinity SARS-CoV-2 spike-specific quantitative IgG and IgM assays in infected, recovered, and vaccinated groups (preprint)

The COVID-19 pandemic continues to impose a significant burden on global health infrastructure. While identification and containment of new cases remains important, laboratories must now pivot and consider assessment of SARS-CoV-2 immunity in the setting of the recent availability of multiple COVID-19 vaccines. Here we have utilized the latest Abbott Alinity semi-quantitative IgM and quantitative IgG spike protein (SP) serology assays (IgMSP and IgGSP) in combination with Abbott Alinity IgG nucleocapsid (NC) antibody test (IgGNC) to assess antibody responses in a cohort of 1236 unique participants comprised of naive, SARS-CoV-2 infected, and vaccinated (including both naive and recovered) individuals. The IgMSP and IgGSP assays were highly specific (100%) with no cross-reactivity to archived samples recovered prior to the emergence of SARS-CoV-2, including those from individuals with seasonal coronavirus infections. Clinical sensitivity was 96% after 15 days for both IgMSP and IgGSP assays individually. When considered together, the sensitivity was 100%. A combination of NC- and SP-specific serologic assays clearly differentiated naive, SARS-CoV-2-infected, and vaccine-related immune responses. Vaccination resulted in a significant increase in IgGSP and IgMSP titers, with a major rise in IgGSP following the booster (second) dose in the naive group. In contrast, SARS-CoV-2 recovered individuals had several fold higher IgGSP responses than naive following the primary dose, with a comparatively dampened response following the booster. This work illustrates the strong clinical performance of these new serological assays and their utility in evaluating and distinguishing serological responses to infection and vaccination.

The Prognostic Value of Myocardial Injury in COVID-19 Patients and Associated Characteristics (preprint)

Background: Since December 2019, Coronavirus disease 2019 (COVID-19) has emerged as an international pandemic. COVID-19 patients with myocardial injury might need special attention. However, understanding on this aspect remains unclear. This study aimed to illustrate clinical characteristics and the prognostic value of myocardial injury to COVID-19 patients. Methods: This retrospective, single-center study finally included 304 hospitalized COVID-19 cases confirmed by real-time RT-PCR from January 11 to March 25, 2020. Myocardial injury was determined by serum high-sensitivity troponin I (Hs-TnI). The primary endpoint was COVID-19 associated mortality. Results: Of 304 COVID-19 patients (median age, 65 years; 52.6% males), 88 patients (27.3%) died (61 patients with myocardial injury, 27 patients without myocardial injury on admission). COVID-19 patients with myocardial injury had more comorbidities (hypertension, chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease); lower lymphocyte counts, higher C-reactive protein (CRP, median, 84.9 vs 28.5 mg/L, p<0.001), procalcitonin levels (median, 0.29 vs 0.06 ng/ml, p<0.001), inflammatory and immune response markers; more frequent need for noninvasive ventilation, invasive mechanical ventilation; and was associated with higher mortality incidence (hazard ratio, HR=7.02, 95% confidence interval, CI, 4.45-11.08, p<0.001) than those without myocardial injury. Myocardial injury (HR=4.55, 95% CI, 2.49-8.31, p<0.001), senior age, CRP levels, and novel coronavirus pneumonia (NCP) types on admission were independent predictors to mortality in COVID-19 patients. Conclusions: COVID patients with myocardial injury on admission is associated with more severe clinical presentation and biomarkers. Myocardial injury and higher HsTNI are both strongest independent predictors to COVID related mortality after adjusting confounding factors. In addition, senior age, CRP levels and NCP types are also associated with mortality. Trial registration: Not applicable.

Efficacy and tolerability of bevacizumab in patients with severe Covid-19.

On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesize that the anti-vascular endothelial growth factor (VEGF) drug bevacizumab might be beneficial for treating Covid-19 patients. From Feb 15 to April 5, 2020, we conducted a single-arm trial (NCT04275414) and recruited 26 patients from 2-centers (China and Italy) with severe Covid-19, with respiratory rate ≥30 times/min, oxygen saturation ≤93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O2 ratio (PaO2/FiO2) >100 mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest imaging. Followed up for 28 days. Among these, bevacizumab plus standard care markedly improves the PaO2/FiO2 ratios at days 1 and 7. By day 28, 24 (92%) patients show improvement in oxygen-support status, 17 (65%) patients are discharged, and none show worsen oxygen-support status nor die. Significant reduction of lesion areas/ratios are shown in chest computed tomography (CT) or X-ray within 7 days. Of 14 patients with fever, body temperature normalizes within 72 h in 13 (93%) patients. Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our findings suggest bevacizumab plus standard care is highly beneficial for patients with severe Covid-19. Randomized controlled trial is warranted.