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1.
Frontiers in medicine ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1871809

ABSTRACT

Objective The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset, that patients first developed symptoms. The potential risk factors were also explored. Methods A cohort of COVID-19 patients discharged from February 20, 2020 to March 31, 2020 was recruited. Follow-ups were conducted using validated questionnaires and psychological screening scales at 15 months after onset to evaluate the patients' health status. The risk factors for long-term health impacts and their associations with disease severity was analyzed. Findings 534 COVID-19 patients were enrolled. The median age of the patients was 62.0 years old (IQR 52.0–70.0) and 295 were female (55.2%). The median time from onset to follow-up was 460.0 (451.0–467.0) days. Sleep disturbance (18.5%, 99/534) and fatigue (17.2%, 92/534) were the most common persistent symptoms. 6.4% (34/534) of the patients had depression, 9.2% (49/534) were anxious, 13.0% (70/534) had insomnia and 4.7% (25/534) suffered from post-traumatic stress disorder (PTSD). Multivariate adjusted logistic regression analysis showed that glucocorticoid use during hospitalization (OR 3.58, 95% CI 1.12–11.44) was significantly associated with an increased risk of fatigue. The OR values for anxiety and sleep disorders were 2.36 (95% CI 1.07–5.20) and 2.16 (95% CI 1.13–4.14) in females to males. The OR value of PTSD was 25.6 (95% CI 3.3–198.4) in patients with persistent symptoms to those without persistent symptoms. No significant associations were observed between fatigue syndrome or adverse mental outcomes and disease severity. Conclusions 15-month follow-up in this study demonstrated the need of extended rehabilitation intervention for complete recovery in COVID-19 patients.

2.
EMBO Mol Med ; 14(5): e14844, 2022 05 09.
Article in English | MEDLINE | ID: covidwho-1776709

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can cause gastrointestinal (GI) symptoms that often correlate with the severity of COVID-19. Here, we explored the pathogenesis underlying the intestinal inflammation in COVID-19. Plasma VEGF level was particularly elevated in patients with GI symptoms and significantly correlated with intestinal edema and disease progression. Through an animal model mimicking intestinal inflammation upon stimulation with SARS-CoV-2 spike protein, we further revealed that VEGF was over-produced in the duodenum prior to its ascent in the circulation. Mechanistically, SARS-CoV-2 spike promoted VEGF production through activating the Ras-Raf-MEK-ERK signaling in enterocytes, but not in endothelium, and inducing permeability and inflammation. Blockage of the ERK/VEGF axis was able to rescue vascular permeability and alleviate intestinal inflammation in vivo. These findings provide a mechanistic explanation and therapeutic targets for the GI symptoms of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Enterocytes/metabolism , Humans , Inflammation/metabolism , Spike Glycoprotein, Coronavirus , Vascular Endothelial Growth Factor A
3.
Front Immunol ; 13: 770982, 2022.
Article in English | MEDLINE | ID: covidwho-1775662

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike protein (S) of SARS-CoV-2 is a major target for diagnosis and vaccine development because of its essential role in viral infection and host immunity. Currently, time-dependent responses of humoral immune system against various S protein epitopes are poorly understood. In this study, enzyme-linked immunosorbent assay (ELISA), peptide microarray, and antibody binding epitope mapping (AbMap) techniques were used to systematically analyze the dynamic changes of humoral immune responses against the S protein in a small cohort of moderate COVID-19 patients who were hospitalized for approximately two months after symptom onset. Recombinant truncated S proteins, target S peptides, and random peptides were used as antigens in the analyses. The assays demonstrated the dynamic IgM- and IgG recognition and reactivity against various S protein epitopes with patient-dependent patterns. Comprehensive analysis of epitope distribution along the spike gene sequence and spatial structure of the homotrimer S protein demonstrated that most IgM- and IgG-reactive peptides were clustered into similar genomic regions and were located at accessible domains. Seven S peptides were generally recognized by IgG antibodies derived from serum samples of all COVID-19 patients. The dynamic immune recognition signals from these seven S peptides were comparable to those of the entire S protein or truncated S1 protein. This suggested that the humoral immune system recognized few conserved S protein epitopes in most COVID-19 patients during the entire duration of humoral immune response after symptom onset. Furthermore, in this cohort, individual patients demonstrated stable immune recognition to certain S protein epitopes throughout their hospitalization period. Therefore, the dynamic characteristics of humoral immune responses to S protein have provided valuable information for accurate diagnosis and immunotherapy of COVID-19 patients.


Subject(s)
COVID-19 , Antibodies, Viral , Epitopes , Humans , Immunity, Humoral , Immunoglobulin G , Immunoglobulin M , Peptides , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
4.
Radiology ; 295(3): 200463, 2020 06.
Article in English | MEDLINE | ID: covidwho-1723927

ABSTRACT

In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, "crazy-paving" pattern and the "reverse halo" sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).


Subject(s)
Coronavirus Infections/diagnostic imaging , Lung Diseases/diagnostic imaging , Lung Diseases/virology , Pneumonia, Viral/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Lung/virology , Lung Diseases/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Radiography, Thoracic/methods , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed/methods , Young Adult
5.
Gut ; 69(6): 997-1001, 2020 06.
Article in English | MEDLINE | ID: covidwho-1723830

ABSTRACT

OBJECTIVE: To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. DESIGN: We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues. RESULTS: Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients. CONCLUSIONS: GI tract may be a potential transmission route and target organ of SARS-CoV-2.


Subject(s)
Betacoronavirus , Coronavirus Infections , Gastrointestinal Tract , Pandemics , Pneumonia, Viral , Adult , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Female , Gastrointestinal Tract/physiopathology , Gastrointestinal Tract/virology , Humans , Male , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , SARS-CoV-2
6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325185

ABSTRACT

Objectives: To retrospectively analyze the most common imaging features on CT at baseline and as they evolve with time as the disease progresses or resolves in a cohort of patients affected with 2019 coronal virus disease (COVID-19) pneumonia in Zhuhai, China.Methods We evaluated 38 patients with COVID-19 in the authors’ institution from Jan 1 to Jan 31, 2020. Cases were confirmed by real-time RT-PCR and were analyzed for epidemiological, demographic, clinical, and radiological features. Outcomes were followed up until Feb 18, 2020. Results 38 initial scans and 62 follow-up scans were obtained. 28 (74%) patients had the history of travel to or residence in Hubei Province of China in 14 days prior to the illness onset. Common findings included ground-glass opacification (GGO), sometimes mixed with consolidation, and interlobular septal and intralobular interstitial thickening. Follow-up imaging often demonstrated peripheral GGO and consolidations spreading to the remainder of the lungs and the increasing consolidative component reflecting the progression of the disease. 8 patients (21%) whose swabs or serum were positive for COVID-19 had no imaging findings on CT throughout the disease course. After treatment the serum and sputum tests became negative for COVID-19 in 32(84%) cases. 28(74%) patients were discharged and three (8%) of them were transferred to the Observation Ward, while seven (18%) patients were kept in Isolation Ward. Conclusion The commonest pattern observed was GGO alone or GGO mixed with consolidation predominantly in lower and peripheral lungs. The follow-up CT scan is crucial for the diagnosis and evaluation of the disease process.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325179

ABSTRACT

Objectives: To retrospectively analyze the CT imaging features and patterns at baseline and as they evolve with time as the disease progresses or resolves in a cohort of pediatric patients affected with 2019 corona virus disease (COVID-19) pneumonia from three different cities in China. Methods: We evaluated 29 pediatric patients with COVID-19 in the authors’ institution from Jan 1 to Feb 20, 2020. Cases were confirmed by laboratory test and were analyzed for epidemiological, demographic, clinical, radiological features and patterns. Results: 29 initial scans and 23 follow-up scans were obtained from 29 patients. 15(52%) patients had been to Hubei Province and 26 (90%) of them had close contact with the COVID-19 positive patients in 14 days prior to the illness onset. The peak severity time was 5-8 days after symptom onset. A significant difference between the number of involved segments at different time points was indicated (p=0.019). Half (52%) of the laboratory confirmed patients had no CT positive findings. Nine (31%) of the laboratory confirmed patients had no symptoms. Six (21%) had no CT positive findings nor symptoms. All the patients of one center(n=6) whose fecal samples remained positive after the respiratory samples became negative. Conclusion: The common positive CT findings included ground-glass opacities (50%), ground-glass opacities mixed with consolidation (36%), peribronchial thickening (21%), and consolidations (14%). We recommend for pediatric patients CT should not be used as a first-line test to diagnose COVID-19.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324967

ABSTRACT

Background: During the outbreak period of COVID-19 pneumonia, cancer patients have been neglected and in greater danger. Furthermore, the differential diagnosis between COVID-19 pneumonia and radiation pneumonitis in caner patients remains a challenge. The study aimed to determine their clinical presentations and radiological features to familiarize radiologists and clinical teams with them in order to early diagnosis and prompt early patient isolation.Methods From January 21, 2019 to February 18, 2020, the patients selected consecutively met the following criteria: (i) presumed COVID-19 pneumonia;(ii) patients with a history of malignancy and lung exposure to ionizing radiation. A retrospective analysis including all patients’ presenting was performed.Results 4 patients from 112 suspected individals were selected, including 2 males and 2 females with a median age of 54 years (39–64 years). After repeated pharyngeal swab nucleic acid tests, 1 case was confirmed and 3 cases were excluded from COVID-19 pneumonia.Conclusions Despite the comparable morphologic characteristics of lung CT imaging, the location, extent, and distribution of lung lesions between COVID-19 pneumonia and radiation pneumonitis differ significantly, further combined with clinical and laboratory findings that could facilitate early diagnosis and appropriate management.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324431

ABSTRACT

Background: Gut ecosystem has profound effects on host physiology and health. Gastrointestinal (GI) symptoms were frequently observed in patients with COVID-19. Compared with other organs, gut antiviral response can result in more complicated immune responses because of the interactions between the gut microbiota and host immunity. However, there are still large knowledge gaps in the impact of COVID-19 on gut molecular profiles and commensal microbiome, hindering our comprehensive understanding of the pathogenesis of SARS-CoV-2 and the treatment of COVID-19. Results: : We performed longitudinal stool multi-omics profiling to systemically investigate the molecular phenomics alterations of gut ecosystem in COVID-19. Gut proteomes of COVID-19 were characterized by disturbed immune, proteolysis and redox homeostasis. The expression and glycosylation of proteins involved in neutrophil degranulation and migration were suppressed, while those of proteases were upregulated. The variable domains of Ig heavy chains were downregulated and the overall glycosylation of IgA heavy chain constant regions, IgGFc-binding protein, and J chain were suppressed with glycan-specific variations. There was a reduction of beneficial gut bacteria and an enrichment of bacteria derived deleterious metabolites potentially associated with multiple types of diseases (such as ethyl glucuronide). The reduction of Ig heave chain variable domains may contribute to the increase of some Bacteroidetes species. Many bacteria ceramide lipids with a C17-sphingoid based were downregulated in COVID-19. In many cases, the gut phenome did not restore two months after symptom onset. Conclusions: : Our study indicates widely disturbed gut molecular profiles which may play a role in the development of symptoms in COVID-19. Our findings also emphasis the need for ongoing investigation of the long-term gut molecular and microbial alterations during COVID-19 recovery process. Considering the gut ecosystem as a potential target could offer a valuable approach in managing the disease.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324219

ABSTRACT

Background: Molecular imaging specifically detecting SARS-CoV-2 in live subjects may aid theranostics for Coronavirus Disease 2019 (COVID-19). Herein, we developed novel molecular probes, Cy5-EK1 and [64 Cu]-NOTA-EK1, based on 36-mer EK1 peptide derived from the S2 subunit of spike (S) protein of SARS-CoV-2, an element of the six-helix bundle of S-protein for virus entry in vivoMethods: Enzyme-linked immunosorbent assay (ELISA) and immunostaining were performed to evaluate the potency of binding between these probes and recombinant full-length S-protein in vitro. HEK293 cells expressing S-protein of SARS-CoV-2 tumor-bearing mouse models were established to test the imaging target engagement in vivo.Findings: The potency of binding between NOTA-EK1 and S-protein was very strong, for which K d was 3.56 ± 0.38 nM and IC50 was 15.7 ± 0.6 nM. The uptake of [64Cu]-NOTA-EK1 in S-protein-positive tumors was greatly increased as early as 1 h post-injection and maintained at a high level until 24 h, while no signal was observed for S-protein-negative tumors. These differences were further confirmed by ex vivo imaging from both fluorescence and PET post-imaging studies. Immunofluorescent staining confirmed the colocalization of Cy5-EK1 with cell surface S-protein of SARS-CoV-2 in S-protein-positive HEK293 cells.Interpretation: Cy5-EK1 and [ 64Cu]-NOTA-EK1 could be used as specific molecular imaging probes for tracking SARS-CoV-2, which may have potential for the imaging and quantification of COVID-19 in a clinical context.Funding: This work was financially supported by the National Key R&D Program of China (2018YFC0910600).Declaration of Interest: None to declare. Ethical Approval: All animal experiments were carried out in accordance with the Institutional Ethical Guidelines for Animal Experiments of the Fifth Affiliated Hospital of Sun Yat-sen University(approval number: 00065).

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322986

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is a worldwide public health pandemic with a high mortality rate, among severe cases. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. It is important to ensure early detection of the virus to curb disease progression to severe COVID-19. This study aimed to establish a clinical-nomogram model to predict the progression to severe COVID-19 in a timely, efficient manner. Methods This retrospective study included 202 patients with COVID-19 who were admitted to the Fifth Affiliated Hospital of Sun Yat-sen University and Shiyan Taihe Hospital from January 17 to April 30, 2020. The patients were randomly assigned to the training dataset (n = 163, with 43 progressing to severe COVID-19) or the validation dataset (n = 39, with 10 progressing to severe COVID-19) at a ratio of 8:2. The optimal subset algorithm was applied to filter for the clinical factors most relevant to the disease progression. Based on these factors, the logistic regression model was fit to distinguish severe (including severe and critical cases) from non-severe (including mild and moderate cases) COVID-19. Sensitivity, specificity, and area under the curve (AUC) were calculated using the R software package to evaluate prediction performance. A clinical nomogram was established and performance assessed with the discrimination curve. Results Risk factors, including demographics data, symptoms, laboratory and image findings were recorded for the 202 patients. Eight of the 52 variables that were entered into the selection process were selected via the best subset algorithm to establish the predictive model;they included gender, age, BMI, CRP, D-dimer, TP, ALB, and involved-lobe. Sensitivity, specificity and AUC were 0.91, 0.84 and 0.86 for the training dataset, and 0.87, 0.66, and 0.80 for the validation dataset. Conclusions We established an efficient and reliable clinical nomogram model which showed that gender, age, and initial indexes including BMI, CRP, D-dimer, involved-lobe, TP, and ALB could predict the risk of progression to severe COVID-19.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322985

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the leading cause of a public health emergency in the world, accompanying with high mortality in severe corona virus disease 2019(COVID-19 ), thereby early detection and stopping the progress to severe COVID-19 is important. Our aim is to establish a clinical nomogram model to calculate and predict the progress to severe COVID-19 timely and efficiently. Methods: In this study, 65 patients with COVID-19 had been included retrospectively in the Fifth Affiliated Hospital of Sun Yat-sen University from January 17, to February 11, 2020. Patients were randomly assigned to train dataset (n=51 with 15 progressing to severe COVID-19) and test dataset (n=14 with 4 progressing to severe COVID-19). Lasso algorithm was applied to filter the most classification relevant clinical factors. Based on selected factors, logistic regression model was fit to predict the severe from mild/common. Meanwhile in nomogram sensitivity, specificity, AUC (Area under Curve), and calibration curve were depicted and calculated by R language, to evaluate the prediction performance to severe COVID-19. Results: High ratio of sever COVID-19 patients (26.5%) had been found in our retrospective study, and 84% of these cases progress to severe or critical after 5 days from their first clinical examination. In these 65 patients with COVID-19, 77 clinical characteristics in first examination were collected and analyzed, and 37 ones had been found different between non-severe and severe COVID-19. But when all these factors were analyzed in establishment of prediction model, six factors are crucial for predicting progress of severe COVID-19 via Lasso algorithm. Based on these six factors, including increased fibrinogen, hyponatremia, decreased PaO2,multiple lung lobes involved, down-regulated CD3(+)T-lymphocyte and fever, a logistic regression model was fit to discriminate severe and common COVID-19 patients. The sensitivity, specificity and AUC were 0.93, 0.86, 0.96 in the train dataset and 0.9, 1.0, 1.0 in test dataset respectively. Nomogram-predicted probability was more consistent with actual probability by R language. Conclusions: In summary, an efficient and reliable clinical nomogram model had been established, which indicate increased fibrinogen, hyponatremia, decreased PaO2, multiple lung lobes involved, down-regulated CD3(+)T-lymphocyte and fever at the first clinical examination, could predict progress of patients to severe COVID-19.

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313733

ABSTRACT

Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who had dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the mAb with the highest binding affinity (nCoV396) revealed changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyper-activation analysis demonstrated that nCoV396 specifically compromises the N protein-induced complement hyper-activation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312747

ABSTRACT

Objective: This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. Methods: A prospective retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-minute walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. Results: 57 patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p=0.019), higher lung total severity score(TSS)and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. Conclusion: Impaired diffusing-capacityDeclining DLCO, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312703

ABSTRACT

Background: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and has since rapidly spread throughout China. The mortality rates of novel coronavirus pneumonia (NCP) in severe and critical cases are very high. In this public-health emergency, a high-efficiency administrative emergency-response mode in designated hospitals is needed. Method: As an affiliated hospital of Sun Yat-sen University, ours, the Fifth Affiliated Hospital, is the only one designated for the diagnosis and treatment of COVID-19 in Zhuhai, a mid-sized city. The NCP department, for which the president of the hospital is also the direct administrative lead, was established at an early stage of the epidemic at our hospital. This department includes core members of the pulmonary and critical-care medicine (PCCM) specialist and multidisciplinary team. Rather than adhering to national guidelines on NCP, we have focused on individualized treatment, timely adjustment thereof and management strategies in working with COVID-19 patients based on the professional opinions of a professor of respiratory medicine and an expert group. Results: (1) High working efficiency: As of March 2, 2020, we have completed 2974 citywide consultations and treatment of 366 inpatients, including 101 who were diagnosed with COVID-19. (2) Excellent therapeutic effect: Of the 101 patients hospitalized with confirmed COVID-19, only 1 has died, and the rest were all cured and discharged. No secondary hospital infection, pipeline infection or pressure sores were found in any patient. (3) Finding and confirming person-to-person transmission characteristic of COVID-19 prior to the official press conference: Strengthened protection is key to zero infection among the healthcare providers and medical faculty, as well as to a lower rate of second-generation infectious patients. (4) Timely adjustment of management and treatment strategy prior to guideline updates: The first evidence of digestive-tract involvement in COVID-19 has been found, and the earliest clinical trial of chloroquine in the treatment of the disease was carried out at our hospital. Conclusions: At our hospital, establishment of an NCP department, which is directly administered by the hospital president and specialized operation guided by a professor of respiratory medicine, has been key to our success in managing and treating COVID-19 patients. Our hospital’s emergency-response mode could provide a reference for other hospitals and cities in this epidemic situation.

16.
Mol Ther Nucleic Acids ; 27: 751-762, 2022 Mar 08.
Article in English | MEDLINE | ID: covidwho-1586912

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a serious impact on the world. In this study, small RNAs from the blood of COVID-19 patients with moderate or severe symptoms were extracted for high-throughput sequencing and analysis. Interestingly, the levels of a special group of tRNA-derived small RNAs (tsRNAs) were found to be dramatically upregulated after SARS-CoV-2 infection, particularly in coronavirus disease 2019 (COVID-19) patients with severe symptoms. In particular, the 3'CCA tsRNAs from tRNA-Gly were highly consistent with the inflammation indicator C-reactive protein (CRP). In addition, we found that the majority of significantly changed microRNAs (miRNAs) were associated with endoplasmic reticulum (ER)/unfolded protein response (UPR) sensors, which may lead to the induction of proinflammatory cytokine and immune responses. This study found that SARS-CoV-2 infection caused significant changes in the levels of stress-associated small RNAs in patient blood and their potential functions. Our research revealed that the cells of COVID-19 patients undergo tremendous stress and respond, which can be reflected or regulated by small non-coding RNA (sncRNAs), thus providing potential thought for therapeutic intervention in COVID-19 by modulating small RNA levels or activities.

18.
Sci Adv ; 7(50): eabi6802, 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1559211

ABSTRACT

Limited understanding of T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impeded vaccine development and drug discovery for coronavirus disease 2019 (COVID-19). We found that triggering receptor expressed on myeloid cells 2 (TREM-2) was induced in T cells in the blood and lungs of patients with COVID-19. After binding to SARS-CoV-2 membrane (M) protein through its immunoglobulin domain, TREM-2 then activated the CD3ζ/ZAP70 complex, leading to STAT1 phosphorylation and T-bet transcription. In vitro stimulation with M protein-reconstituted pseudovirus or recombinant M protein, and TREM-2 promoted the T helper cell 1 (TH1) cytokines interferon-γ and tumor necrosis factor. In vivo infection of CD4­TREM-2 conditional knockout mice with murine coronavirus mouse hepatitis virus A-59 showed that intrinsic TREM-2 in T cells enhanced TH1 response and viral clearance, thus aggravating lung destruction. These findings demonstrate a previously unidentified role for TREM-2 in SARS-CoV-2 infection, and suggest potential strategies for drug discovery and clinical management of COVID-19.

19.
J Nanobiotechnology ; 19(1): 391, 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1538075

ABSTRACT

BACKGROUND: Considering the threat of the COVID-19 pandemic, caused by SARS-CoV-2, there is an urgent need to develop effective treatments. At present, neutralizing antibodies and small-molecule drugs such as remdesivir, the most promising compound to treat this infection, have attracted considerable attention. However, some potential problems need to be concerned including viral resistance to antibody-mediated neutralization caused by selective pressure from a single antibody treatment, the unexpected antibody-dependent enhancement (ADE) effect, and the toxic effect of small-molecule drugs. RESULTS: Here, we constructed a type of programmed nanovesicle (NV) derived from bispecific CAR-T cells that express two single-chain fragment variables (scFv), named CR3022 and B38, to target SARS-CoV-2. Nanovesicles that express both CR3022 and B38 (CR3022/B38 NVs) have a stronger ability to neutralize Spike-pseudovirus infectivity than nanovesicles that express either CR3022 or B38 alone. Notably, the co-expression of CR3022 and B38, which target different epitopes of spike protein, could reduce the incidence of viral resistance. Moreover, the lack of Fc fragments on the surface of CR3022/B38 NVs could prevent ADE effects. Furthermore, the specific binding ability to SARS-CoV-2 spike protein and the drug loading capacity of CR3022/B38 NVs can facilitate targeted delivery of remdesiver to 293 T cells overexpressing spike protein. These results suggest that CR3022/B38 NVs have the potential ability to target antiviral drugs to the main site of viral infection, thereby enhancing the antiviral ability by inhibiting intracellular viral replication and reducing adverse drug reactions. CONCLUSIONS: In summary, we demonstrate that nanovesicles derived from CAR-T cells targeting the spike protein of SARS-COV-2 have the ability to neutralize Spike-pseudotyped virus and target antiviral drugs. This novel therapeutic approach may help to solve the dilemma faced by neutralizing antibodies and small-molecule drugs in the treatment of COVID-19.


Subject(s)
COVID-19/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Antibodies, Viral/immunology , Antibodies, Viral/metabolism , Antiviral Agents/therapeutic use , COVID-19/immunology , Humans , Models, Theoretical
20.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-291513

ABSTRACT

Background: The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset. The potential risk factors were also explored.Methods: A cohort of COVID-19 patients discharged from February 20, 2020 to March 31, 2020 was recruited. Follow-ups were conducted using validated questionnaires and psychological screening scales at 15 months after onset to evaluate the patients’ health status. The risk factors for long-term health impacts and their associations with disease severity was analyzed.Findings: 534 COVID-19 patients were enrolled. The median age of the patients was 62.0 years old (IQR 52.0-70.0) and 295 were female (55.2%). The median time from onset to follow-up was 460.0 (451.0-467.0) days. Sleep disturbance (18.5%, 99/534) and fatigue (17.2%, 92/534) were the most common persistent symptoms. 6.4% (34/534) of the patients had depression, 9.2% (49/534) were anxious, 13.0% (70/534) had insomnia and 4.7% (25/534) suffered from posttraumatic stress disorder (PTSD). Multivariate adjusted logistic regression analysis showed that glucocorticoid use during hospitalization (OR 3.58, 95% CI 1.12-11.44) was significantly associated with an increased risk of fatigue. The OR values for anxiety and sleep disorders were 2.36 (95% CI 1.07-5.20) and 2.16 (95% CI 1.13-4.14) in females compared with males. The OR value of PTSD was 25.6 (95% CI 3.3-198.4) in patients with persistent symptoms to those without persistent symptoms. No significant associations were observed between fatigue syndrome or adverse mental outcomes and disease severity.Interpretation: 15-month follow-up in this study aroused the need of extended rehabilitation intervention for complete recovery in COVID-19 patients. Funding: None to declare. Declaration of Interest: All the authors declare no competing interests.Ethical Approval: The Research Ethics Committee of Shanghai Changzheng Hospital approved this study (2020SL007).

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