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1.
J Leukoc Biol ; 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-757823

ABSTRACT

Regulatory T cell can protect against severe forms of coronaviral infections attributable to host inflammatory responses. But its role in the pathogenesis of COVID-19 is still unclear. In this study, frequencies of total and multiple subsets of lymphocytes in peripheral blood of COVID-19 patients and discharged individuals were analyzed using a multicolor flow cytometry assay. Plasma concentration of IL-10 was measured using a microsphere-based immunoassay kit. Comparing to healthy controls, the frequencies of total lymphocytes and T cells decreased significantly in both acutely infected COVID-19 patients and discharged individuals. The frequencies of total lymphocytes correlated negatively with the frequencies of CD3- CD56+ NK cells. The frequencies of regulatory CD8+ CD25+ T cells correlated with CD4+ /CD8+ T cell ratios positively, while the frequencies of regulatory CD4+ CD25+ CD127- T cells correlated negatively with CD4+ /CD8+ T cell ratios. Ratios of CD4+ /CD8+ T cells increased significantly in patients beyond age of 45 years. And accordingly, the frequencies of regulatory CD8+ CD25+ T cells were also found significantly increased in these patients. Collectively, the results suggest that regulatory CD4+ and CD8+ T cells may play distinct roles in the pathogenesis of COVID-19. Moreover, the data indicate that NK cells might contribute to the COVID-19 associated lymphopenia.

2.
J Clin Lab Anal ; : e23535, 2020 Aug 25.
Article in English | MEDLINE | ID: covidwho-728091

ABSTRACT

BACKGROUND: This objective of this study was to identify a sensitive indicator of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Samples were collected from 136 patients with Coronavirus disease 2019 (COVID-19) pneumonia admitted to the Shanghai public health clinical center (116 mild, 20 severe). The concentrations of serum urea, Uric Acid (UA), Creatinine (CREA), Erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), procalcitonin (PCT), and urine protein (Pro) have been tested in this study. RESULTS: Higher levels of urea (female 7.00 ± 3.31, male 8.87 ± 5.18) Pro (female7/7, male 12/13), hs-CRP (female 2/7, male 5/13) ESR (female 94.43 ± 33.26, male 67.85 ± 22.77) were found in severe patients compared with the mild (urea: female 3.71 ± 1.00, male 4.42 ± 1.14; Pro: female 3/46, male 12/70; hs-CRP: female 1/46, male 3/70; ESR: female 43.32 ± 33.24, male 21.64 ± 21.82). UA is lower in the severe group (female 146.90 ± 54.01, male 139.34 ± 66.95) than in mild group (female 251.99 ± 64.35, male 339.81 ± 71.32). CREA and PCT did not show a significant difference between mild and severe patients, but the difference among the five biological markers (urea, Pro, hs-CRP, ESR, and UA) between mild and severe patients we tested was small (P < .05). CONCLUSION: Severe COVID-19 patients had higher levels of urea and Pro, while their UA levels were lower, reflecting poor kidney function in severe patients. However, higher levels of hs-CRP, ESR indicated that inflammatory responses were more active in severe patients.

3.
Emerg Microbes Infect ; 9(1): 1958-1964, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-725886

ABSTRACT

Objectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections (P<0.0001). The most common infections were respiratory, blood-stream and urinary infections, and in respiratory infections, the most detected pathogens were gram-negative bacteria (26, 50.00%), following by gram-positive bacteria (14, 26.92%), virus (6, 11.54%), fungi (4, 7.69%), and others (2, 3.85%). Respiratory Infection rate post high flow, tracheal intubation, and tracheotomy were 12.90% (4/31), 30.43% (7/23), and 92.31% (12/13) respectively. Secondary infections would lead to lower discharge rate and higher mortality rate. Conclusion Our study originally illustrated secondary infection proportion in severe and critical COVID-19 patients. Culture accompanied with metagenomics sequencing increased pathogen diagnostic rate. Secondary infections risks increased after receiving invasive respiratory ventilations and intravascular devices, and would lead to a lower discharge rate and a higher mortality rate.


Subject(s)
Bacteremia/pathology , Bacterial Infections/pathology , Coronavirus Infections/pathology , Fungemia/pathology , Mycoses/pathology , Opportunistic Infections/pathology , Pneumonia, Viral/pathology , Respiratory Tract Infections/pathology , Urinary Tract Infections/pathology , Aged , Bacteremia/microbiology , Bacteremia/mortality , Bacteremia/virology , Bacterial Infections/microbiology , Bacterial Infections/mortality , Bacterial Infections/virology , Betacoronavirus/pathogenicity , Coronavirus Infections/microbiology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Critical Illness , Female , Fungemia/microbiology , Fungemia/mortality , Fungemia/virology , Fungi/pathogenicity , Gram-Negative Bacteria/pathogenicity , Gram-Positive Bacteria/pathogenicity , Humans , Intensive Care Units , Lung/microbiology , Lung/pathology , Lung/virology , Male , Middle Aged , Mycoses/microbiology , Mycoses/mortality , Mycoses/virology , Opportunistic Infections/microbiology , Opportunistic Infections/mortality , Opportunistic Infections/virology , Pandemics , Pneumonia, Viral/microbiology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Respiration, Artificial/adverse effects , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/mortality , Respiratory Tract Infections/virology , Retrospective Studies , Risk , Severity of Illness Index , Survival Analysis , Urinary Tract Infections/microbiology , Urinary Tract Infections/mortality , Urinary Tract Infections/virology
4.
Med (N Y) ; 2020 Jul 21.
Article in English | MEDLINE | ID: covidwho-664427

ABSTRACT

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. Methods: Genome-wide screening was used to establish intraviral and viral-host interactomes. Quantitative proteomics was used to investigate the peripheral blood mononuclear cell (PBMC) proteome signature in COVID-19. Findings: We elucidated 286 host proteins targeted by SARS-CoV-2 and >350 host proteins that are significantly perturbed in COVID-19-derived PBMCs. This signature in severe COVID-19 PBMCs reveals a significant upregulation of cellular proteins related to neutrophil activation and blood coagulation, as well as a downregulation of proteins mediating T cell receptor signaling. From the interactome, we further identified that non-structural protein 10 interacts with NF-κB-repressing factor (NKRF) to facilitate interleukin-8 (IL-8) induction, which potentially contributes to IL-8-mediated chemotaxis of neutrophils and the overexuberant host inflammatory response observed in COVID-19 patients. Conclusions: Our study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks but it also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms, representing a powerful resource in the pursuit of therapeutic interventions. Funding: National Key Research and Development Project of China, National Natural Science Foundation of China, National Science and Technology Major Project, Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission, Shanghai Municipal Key Clinical Specialty, Innovative Research Team of High-level Local Universities in Shanghai, Interdisciplinary Program of Shanghai Jiao Tong University, SII Challenge Fund for COVID-19 Research, Chinese Academy of Sciences (CAS) Large Research Infrastructure of Maintenance and Remolding Project, and Chinese Academy of Sciences Key Technology Talent Program.

5.
Emerg Microbes Infect ; 9(1): 1537-1545, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-611841

ABSTRACT

Background: Novel coronavirus pneumonia (COVID-19) is prevalent around the world. We aimed to describe epidemiological features and clinical course in Shanghai. Methods: We retrospectively analysed 325 cases admitted at Shanghai Public Health Clinical Center, between January 20 and February 29, 2020. Results: 47.4% (154/325) had visited Wuhan within 2 weeks of illness onset. 57.2% occurred in 67 clusters; 40% were situated within 53 family clusters. 83.7% developed fever during the disease course. Median times from onset to first medical care, hospitalization and negative detection of nucleic acid by nasopharyngeal swab were 1, 4 and 8 days. Patients with mild disease using glucocorticoid tended to have longer viral shedding in blood and feces. At admission, 69.8% presented with lymphopenia and 38.8% had elevated D-dimers. Pneumonia was identified in 97.5% (314/322) of cases by chest CT scan. Severe-critical patients were 8% with a median time from onset to critical disease of 10.5 days. Half required oxygen therapy and 7.1% high-flow nasal oxygen. The case fatality rate was 0.92% with median time from onset to death of 16 days. Conclusion: COVID-19 cases in Shanghai were imported. Rapid identification, and effective control measures helped to contain the outbreak and prevent community transmission.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Female , Follow-Up Studies , Health Status Indicators , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Retrospective Studies , Time Factors , Treatment Outcome , Virus Shedding , Young Adult
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