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1.
PLoS Genet ; 18(4): e1010137, 2022 04.
Article in English | MEDLINE | ID: covidwho-1789166

ABSTRACT

Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.


Subject(s)
COVID-19 , Alternative Splicing/genetics , COVID-19/genetics , COVID-19 Testing , Humans , Proteomics , SARS-CoV-2/genetics , Transcriptome
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311945

ABSTRACT

Background: Imported COVID-19 cases are a serious public health problem worldwide. However, limited epidemiologic information of imported cases affects the choice of prevention and control strategies.Methods: In this study, we collected data from 22 January 2020 to 21 April 2020 related to imported COVID-19 cases in Mainland China from the daily public data of the National Health Commission and the provincial health commissions.Findings: A total of 1610 cases of COVID-19 were imported from 49 countries and regions to 27 provincial administrative regions. 79.81% cases were imported from European countries and the United States. Before 29 March, the imported cases were mainly from the United States (27.66%) and United Kingdom (42.55%). After 29 March 2020, the daily newly imported cases from Russia rapidly growed. After 12 April, the number of daily newly imported cases gradually decreased and remained at a low level (12±7 cases per day). Airport entry was encouraged and ground crossing entry was limited with the help of dynamic surveillance of the weekly proportion of confirmed cases at ports. 54.04% imported confirmed cases were in the asymptomatic incubation period on arrival in Mainland China. The compulsory centralized quarantine decreased the risk of onward transmission from imported cases compared to home quarantine ( P <0.05).Interpretation: Prevention and control strategies based on the epidemiological characteristics of imported cases effectively protected Mainland China against reintroduction of the virus and re-initiation of the epidemic when the epidemic was still in a surge worldwide. Such measures included: exit screening, entry screening, and compulsory centralized quarantine of all inbound travelers followed by strict contact tracing. The experiences from Mainland China provide an example of effective measures to reduce transmission of imported COVID-19 cases.Funding Statement: Shanghai Science and Technology Commission, Pudong Health Bureau of Shanghai and Krebsliga Schweiz, BIL KFS. Declaration of Interests: None to be declared.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325501

ABSTRACT

Background: Many COVID-19 patients have been discharged, but lung injury, including pulmonary fibrosis, might lead to long-term impairment. This study aimed to evaluate predictors and monitors of pulmonary fibrosis in patients with COVID-19. Methods Thirty-five convalescent patients with severe COVID-19, after appropriate medical treatments, were recruited. According to evidence of fibrosis on initial computed tomography (CT), the patients were divided into mild-to-moderate and severe groups. Levels of transforming growth factor beta (TGF-β), chemokine ligand 18 (CCL18), type III procollagen peptide (PⅢP), hyaluronic acid (HA), laminin (LN), and type IV collagen (CⅣ) were determined. Laboratory tests, clinical data, and CT features at different stages were collected and analyzed, and the prognostic performance of these parameters was evaluated. Results Severe fibrosis was found in 76.29% (26/35) of patients. However, most baseline laboratory characteristics were normal. Fibrosis indicators (TGF-β: 66.67 ± 158.57 vs 55.84 ± 126.43 pg/mL, P = 0.006;CCL18: 364.27 ± 167.70 vs 84.47 ± 60.67 ng/mL, P = 0.000;PⅢP: 54.12 ± 55.34 vs 17.15 ± 2.48 ng/mL, P = 0.000;HA: 122.47 ± 78.84 vs 59.74 ± 18.01 ng/mL, p = 0.000;LN: 55.43 ± 46.44 vs 24.25 ± 7.79 ng/mL, P = 0.000;CⅣ: 24.77 ± 14.97 vs 15.32 ± 1.15 ng/mL, P = 0.001) were elevated in patients compared with controls. Over 90 days’ follow-up, HRCT scores gradually decreased from 22.48 ± 16.13 to 10.33 ± 11.11 (P < 0.001), and mMRC scores decreased from 3.27 ± 0.32 to 1.48 ± 0.33, and all fibrosis indicators, except for PⅢP, gradually declined with the improvement of pulmonary fibrosis. Moreover, TGF-β and CCL18 levels were lower in the mild-to-moderate than severe fibrosis group (88.16 ± 97.45 vs 205.93 ± 170.57 pg/mL, P = 0.024;241.84 ± 125.37 vs 366.64 ± 161.06 ng/mL, P = 0.038), and patients with elevated baseline levels of serum TGF-β and CCL18 had longer rehabilitation times. Conclusions TGF-β and CCL18 may be promising biomarkers for predicting and monitoring the development of pulmonary fibrosis in patients with COVID-19.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325337

ABSTRACT

Background: The COVID-19 has high transmission and mortality. Previous studies support the efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of lung injury. In this study, We aimed to evaluate the CT changes of lung lesions in severe COVID-19 patients treated with umbilical cord mesenchymal stem cells (UC-MSCs) by using AI-assisted quantification method.Methods46 patients with severe COVID-19 from March 5 to April 1, 2020 were selected by single-blind, non-randomized controlled clinical study and divided into three groups: 11 cases in UC-MSCs treatment group 1 (MSC-1, with cells infusion once), 26 cases in UC-MSCs treatment group 2 (MSC-2, with cells infusion twice or three times), and 9 cases in control group with routine treatment. Repeated measure ANOVA was used to compare the effects of treatment factors on chest CT parameters of COVID-19 patients between control and experimental groups, and pairwise comparison using LSD test.FindingsThe differences between the percentage of GGO in total lung or the percentage of total lung infection volume on day 0 and that in day 60 as well as in day 90 were statistically significant among the three groups. The P values were 0.034 and 0.018 respectively. Pairwise comparison results showed that the percentage difference of the whole lung GGO and total lung infection volume in MSC-1 group was smaller than that in control group and MSC-2 group respectively, but there was no statistical difference between control group and MSC-2 group. The distribution characteristics and other CT parameters post-proceeded by AI software were not significantly different among the three groups. There were no serious adverse events related to stem cell infusion in all treated patients.InterpretationUC-MSC infusion is safe for the treatment of severe COVID-19 patients. The absorption of lung lesions at 60 days and 90 days after UC-MSC infusion once was more obvious than that in the control group. AI quantification of lung lesions is more suitable for comparative studies before and after treatment.

6.
Front Med (Lausanne) ; 8: 697338, 2021.
Article in English | MEDLINE | ID: covidwho-1555527

ABSTRACT

Covid-19, Coronavirus disease 2019; ARDS, Acute respiratory distress syndrome; ECMO, Extracorporeal Membrane Oxygenation; WHO, World Health Organization; ICUs, Intensive care units. Acute respiratory distress syndrome (ARDS) is a fatal comorbidity of critically ill patients with COVID-19, who often end up on respiratory support. However, the safety and effectiveness of Extracorporeal Membrane Oxygenation (ECMO) in the treatment of COVID-19 remains to be elucidated at present. Here, we report on nine patients who received ECMO due to severe SARS-CoV-2 infection in Wuhan, China. Our initial experiences suggest that carefully selecting patients, as well as management by a well-trained team, are critical to implementing ECMO in patients with COVID-19. More randomized controlled trials with larger sample sizes are needed to evaluate the usefulness of ECMO in patients with COVID-19.

7.
Nat Commun ; 12(1): 7083, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1555251

ABSTRACT

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.


Subject(s)
Atlases as Topic , Single-Cell Analysis/veterinary , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Birds , Cell Communication , Evolution, Molecular , Gene Regulatory Networks , Host-Pathogen Interactions , Lung/cytology , Lung/metabolism , Lung/virology , Mammals , Receptors, Virus/genetics , Receptors, Virus/metabolism , Reptiles , SARS-CoV-2/metabolism , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Transcriptome , Viral Tropism , Virus Internalization
8.
Cell Discov ; 7(1): 99, 2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1483126

ABSTRACT

Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8+ T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders.

9.
Brief Bioinform ; 22(2): 976-987, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343642

ABSTRACT

Emerging viral infections seriously threaten human health globally. Several challenges exist in identifying effective compounds against viral infections: (1) at the initial stage of a new virus outbreak, little information, except for its genome information, may be available; (2) although the identified compounds may be effective, they may be toxic in vivo and (3) cytokine release syndrome (CRS) triggered by viral infections is the primary cause of mortality. Currently, an integrative tool that takes all those aspects into consideration for identifying effective compounds to prevent viral infections is absent. In this study, we developed iDMer, as an integrative and mechanism-driven response system for addressing these challenges during the sudden virus outbreaks. iDMer comprises three mechanism-driven compound identification modules, that is, a virus-host interaction-oriented module, an autophagy-oriented module and a CRS-oriented module. As a one-stop integrative platform, iDMer incorporates compound toxicity evaluation and compound combination identification for virus treatment with clear mechanisms. iDMer was successfully tested on five viruses, including the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results indicated that, for all five tested viruses, compounds that were reported in the literature or experimentally validated for virus treatment were enriched at the top, demonstrating the generalized effectiveness of iDMer. Finally, we demonstrated that combinations of the individual modules successfully identified combinations of compounds effective for virus intervention with clear mechanisms.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Algorithms , Autophagy , COVID-19/virology , Host Microbial Interactions , Humans , SARS-CoV-2/isolation & purification , Sequence Analysis, RNA
10.
Signal Transduct Target Ther ; 6(1): 213, 2021 05 31.
Article in English | MEDLINE | ID: covidwho-1249203

ABSTRACT

Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core-shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/therapeutic use , Female , Humans , Immunogenicity, Vaccine/immunology , Lymphocyte Activation/immunology , Mice , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Th1 Cells/immunology , Th1 Cells/virology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Viral Vaccines/immunology
11.
Blood Purif ; 50(4-5): 499-505, 2021.
Article in English | MEDLINE | ID: covidwho-962803

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). However, the epidemiological features and outcomes of AKI among COVID-19 patients with ARDS are unknown. METHODS: We retrospectively recruited consecutive adult COVID-19 patients who were diagnosed with ARDS according to Berlin definition from 13 designated intensive care units in the city of Wuhan, China. Potential risk factors of AKI as well as the relation between AKI and in-hospital mortality were investigated. RESULTS: A total of 275 COVID-19 patients with ARDS were included in the study, and 49.5% of them developed AKI during their hospital stay. In comparison with patients without AKI, patients who developed AKI were older, tended to have chronic kidney disease, had higher Sepsis-Related Organ Failure Assessment score on day 1, and were more likely to receive invasive ventilation and develop acute organ dysfunction. Multivariate analysis showed that age, history of chronic kidney disease, neutrophil-to-lymphocyte ratio, and albumin level were independently associated with the occurrence of AKI. Importantly, increasing AKI severity was associated with increased in-hospital mortality when adjusted for other potential variables: odds ratio of stage 1 = 5.374 (95% CI: 2.147-13.452; p < 0.001), stage 2 = 6.216 (95% CI: 2.011-19.210; p = 0.002), and stage 3 = 34.033 (95% CI: 9.723-119.129; p < 0.001). CONCLUSION: In this multicenter retrospective study, we found that nearly half of COVID-19 patients with ARDS experienced AKI during their hospital stay. The coexistence of AKI significantly increased the mortality of these patients.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/complications , Hospital Mortality , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Acute Kidney Injury/blood , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Aged , China/epidemiology , Comorbidity , Creatinine/blood , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Renal Insufficiency, Chronic/complications , Respiration, Artificial/adverse effects , Respiration, Artificial/statistics & numerical data , Respiratory Distress Syndrome/therapy , Retrospective Studies , Risk Factors
13.
BMJ Glob Health ; 5(6)2020 06.
Article in English | MEDLINE | ID: covidwho-603209

ABSTRACT

Since the COVID-19 outbreak, Wuhan has adopted three methods of admitting patients for treatment: designated hospitals, newly built temporary hospitals and Fangcang shelter hospitals. It has been proven that converting large-scale public venues such as stadiums and exhibition centres into Fangcang shelter hospitals, which serve as hospitals for isolation, treatment and disease monitoring of patients with mild symptoms, is the most effective way to control virus transmission and reduce mortality. This paper presents some experiences learnt from treating COVID-19 in Wuhan, the first city to report the outbreak and which suffered from a shortage of emergency supplies, heavy workload among staff and a shortage of hospital beds during the early stages of the pandemic. The experiences include location, accessibility, spacious outdoor area, spacious indoor space, power supply, architectural layout design and partition isolation, ventilation, sewage, and problems in the construction and management of Fangcang shelter hospitals. During the COVID-19 pandemic, traditional approaches to disaster preparedness have demonstrated intrinsic problems, such as poor economic performance, inefficiency and lack of flexibility. Converting large-scale public venues into Fangcang shelter hospitals is an important means to rapidly improve the function of the city's healthcare system during a pandemic. This valuable experience in Wuhan will help other countries in their battle against the current COVID-19 pandemic and will also contribute to disaster preparedness and mitigation in the future.


Subject(s)
Coronavirus Infections , Disaster Planning , Hospitals, Isolation , Pandemics , Pneumonia, Viral , Public Facilities , Betacoronavirus , COVID-19 , China , Disease Outbreaks , Emergency Shelter , Humans , SARS-CoV-2
14.
ERJ Open Res ; 6(2)2020 Apr.
Article in English | MEDLINE | ID: covidwho-182627

ABSTRACT

BACKGROUND: We aimed to investigate the epidemiological and clinical features, and medical care-seeking process of patients with the 2019 coronavirus disease (COVID-19) in Wuhan, China, to provide useful information to contain COVID-19 in other places with similar outbreaks of the virus. METHODS: We collected epidemiological and clinical information of patients with COVID-19 admitted to a makeshift Fangcang hospital between 7 and 26 February, 2020. The waiting time of each step during the medical care-seeking process was also analysed. RESULTS: Of the 205 patients with COVID-19 infection, 31% had presumed transmission from a family member. 10% of patients had hospital-related transmission. It took as long as a median of 6 days from the first medical visit to receive the COVID-19 nucleic acid test and 10 days from the first medical visit to hospital admission, indicating early recognition of COVID-19 was not achieved at the early stage of the outbreak, although these delays were shortened later. After clinical recovery from COVID-19, which took a mean of 21 days from illness onset, there was still a substantial proportion of patients who had persistent SARS-CoV-2 infection. CONCLUSIONS: The diagnostic evaluation process of suspected patients needs to be accelerated at the epicentre of the outbreak and early isolation of infected patients in a healthcare setting rather than at home is urgently required to stop the spread of the virus. Clinical recovery is not an appropriate criterion to release isolated patients and as long as 4 weeks' isolation for patients with COVID-19 is not enough to prevent the spread of the virus.

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