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1.
Int J Infect Dis ; 118: 65-70, 2022 May.
Article in English | MEDLINE | ID: covidwho-1838853

ABSTRACT

OBJECTIVES: Cross-reactivity with nontuberculous mycobacteria (NTM) species might limit the use of urine lipoarabinomannan (LAM) test to diagnose tuberculosis (TB) in people living with HIV (PLWH). This study aimed to investigate the utility of the LAM test among hospitalized HIV-positive patients. METHODS: This prospective study enrolled HIV-positive inpatients with any TB symptom or seriously ill patients with advanced immunodeficiency. Urine samples were tested using the Alere Determine LAM Ag, and participants were categorized as confirmed TB, confirmed NTM infection, unclassified mycobacteria infection, and no mycobacteria infection based on microbiologic reference standards. RESULTS: A total of 382 participants were included. The prevalence of confirmed TB and NTM infection was 5.24% (20 of 382) and 4.45% (17 of 382), respectively. The sensitivity and specificity of the urine LAM for TB diagnosis were 65.00% (95% confidence interval [CI] 40.78-84.61) and 89.36% (95% CI 85.68-92.36), respectively. The LAM test for NTM yielded a sensitivity of 58.82% (95% CI 32.92-81.56) and specificity of 88.61% (95% CI 84.87-91.70). Notably, the negative predictive values of the urine LAM for TB and NTM were 97.85% (95% CI 95.63-99.13) and 97.85% (95% CI 95.63-99.13), respectively. CONCLUSIONS: Cross-reactivity with NTM cause high false-positive LAM for TB diagnosis in PLWH. The correct identification of mycobacteria species is crucial for deciding treatment strategies.


Subject(s)
HIV Infections , HIV Seropositivity , Mycobacterium Infections, Nontuberculous , Tuberculosis , HIV Infections/epidemiology , Humans , Lipopolysaccharides/urine , Mycobacterium Infections, Nontuberculous/diagnosis , Nontuberculous Mycobacteria , Prospective Studies , Tuberculosis/diagnosis , Tuberculosis/epidemiology
2.
Clin Infect Dis ; 74(4): 729-733, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1328915

ABSTRACT

Emerging infectious disease epidemics require a rapid response from health systems; however, evidence-based consensus guidelines are generally absent early in the course of events. Formed in 2017 by 5 high-level isolation units spanning 3 continents, the experience of the Global Infectious Disease Preparedness Network (GIDPN) early in the course of coronavirus disease 2019 (COVID-19) provides a model for accelerating best practice development and improving decision-making in health emergencies. The network served as a platform for real-time, open and transparent information-sharing during unknowns of an active outbreak by clinicians caring for patients, by researchers conducting clinical trials and transmission and infection prevention studies, and by teams advising local and national policy makers. Shared knowledge led to earlier adoption of some treatment modalities as compared to most peer institutions and to implementation of protocols prior to incorporation into national guidelines. GIDPN and similar networks are integral in enhancing preparedness for and response to future epidemics/pandemics.


Subject(s)
COVID-19 , Communicable Diseases , Communicable Diseases/epidemiology , Communicable Diseases/therapy , Decision Making , Humans , Pandemics/prevention & control , SARS-CoV-2
3.
Front Cell Infect Microbiol ; 11: 653794, 2021.
Article in English | MEDLINE | ID: covidwho-1325515

ABSTRACT

Purpose: To investigate the sensitivity of SARS-CoV-2 testing in specimens collected from the anterior nasal vestibules of COVID-19 patients. Methods: A cross-sectional analysis was performed on 30 patients with a confirmed diagnosis of COVID-19 at the Shanghai Public Health Clinical Center from March 14, 2020 to March 21, 2020. Paired specimens were collected from both the anterior nasal vestibule and the oropharynx from all patients. All specimens were tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) assays. Results: Of the 30 patients with confirmed COVID-19, 17 patients (56.7%) tested positive for SARS-CoV-2 when oropharyngeal specimens were used, while 20 patients (66.7%) tested positive when nasal swab specimens were used. There was no statistically significant difference in sensitivity between the two methods. Conclusions: Respiratory swabs collected from the nasal vestibule offer a less invasive alternative to oropharyngeal swabs for specimen collection in the detection of SARS-CoV-2 infection, and have adequate sensitivity.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , China/epidemiology , Cross-Sectional Studies , Humans , Nasopharynx , Specimen Handling
4.
Front Immunol ; 12: 568789, 2021.
Article in English | MEDLINE | ID: covidwho-1278390

ABSTRACT

Dysregulation of immune response was observed in COVID-19 patients. Thymosin alpha 1 (Tα1) is used in the management of COVID-19, because it is known to restore the homeostasis of the immune system during infections and cancers. We aim to observe the longitudinal changes in T lymphocyte subsets and to evaluate the efficacy of Tα1 for COVID-19. A retrospective study was conducted in 275 COVID-19 patients admitted to Shanghai public health clinical center. The clinical and laboratory characteristics between patients with different T lymphocyte phenotypes and those who were and were not treated with Tα1 were compared. Among the 275 patients, 137 (49.8%) were males, and the median age was 51 years [interquartile range (IQR): 37-64]. A total of 126 patients received Tα1 therapy and 149 patients did not. There were 158 (57.5%) patients with normal baseline CD4 counts (median:631/µL, IQR: 501~762) and 117 patients (42.5%) with decreased baseline CD4 counts (median:271/µL, IQR: 201~335). In those with decreased baseline CD4 counts, more patients were older (p<0.001), presented as critically ill (p=0.032) and had hypertension (p=0.008) compared with those with normal CD4 counts. There was no statistical difference in the duration of virus shedding in the upper respiratory tract between the two groups (p=0.214). In both the normal (14 vs 11, p=0.028) and the decreased baseline CD4 counts group (15 vs 11, p=0.008), duration of virus clearance in the patients with Tα1 therapy was significantly longer than that in those without Tα1 therapy. There was no significant difference in the increase of CD4+ (286 vs 326, p=0.851) and CD8+ T cell (154 vs 170, p=0.842) counts in the recovery period between the two groups with or without Tα1 therapy. Multivariate linear regression analysis showed that severity of illness (p<0.001) and Tα1 therapy (p=0.001) were associated with virus clearance. In conclusion, reduction of CD4+ T and CD8+ T cell counts were observed in COVID-19 patients. Tα1 may have no benefit on restoring CD4+ and CD8+ T cell counts or on the virus clearance. The use of Tα1 for COVID-19 need to be more fully investigated.


Subject(s)
CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/drug effects , COVID-19/drug therapy , Thymalfasin/therapeutic use , Adjuvants, Immunologic/pharmacology , Adult , COVID-19/immunology , China , Female , Humans , Lymphocyte Count , Male , Middle Aged , Retrospective Studies , SARS-CoV-2
5.
J Leukoc Biol ; 109(1): 91-97, 2021 01.
Article in English | MEDLINE | ID: covidwho-1188013

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.


Subject(s)
CD8-Positive T-Lymphocytes , COVID-19 , SARS-CoV-2 , T-Lymphocytes, Regulatory , Adult , Aged , Antigens, CD/blood , Antigens, CD/immunology , CD4-CD8 Ratio , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , COVID-19/blood , COVID-19/immunology , COVID-19/pathology , Female , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/pathology
6.
Front Immunol ; 12: 625881, 2021.
Article in English | MEDLINE | ID: covidwho-1133910

ABSTRACT

T cells play a critical role in coronavirus diseases. How they do so in COVID-19 may be revealed by analyzing the epigenetic chromatin accessibility of cis- and trans-regulatory elements and creating transcriptomic immune profiles. We performed single-cell assay for transposase-accessible chromatin (scATAC) and single-cell RNA (scRNA) sequencing (seq) on the peripheral blood mononuclear cells (PBMCs) of severely ill/critical patients (SCPs) infected with COVID-19, moderate patients (MPs), and healthy volunteer controls (HCs). About 76,570 and 107,862 single cells were used, respectively, for analyzing the characteristics of chromatin accessibility and transcriptomic immune profiles by the application of scATAC-seq (nine cases) and scRNA-seq (15 cases). The scATAC-seq detected 28,535 different peaks in the three groups; among these peaks, 41.6 and 10.7% were located in the promoter and enhancer regions, respectively. Compared to HCs, among the peak-located genes in the total T cells and its subsets, CD4+ T and CD8+ T cells, from SCPs and MPs were enriched with inflammatory pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway and tumor necrosis factor (TNF) signaling pathway. The motifs of TBX21 were less accessible in the CD4+ T cells of SCPs compared with those in MPs. Furthermore, the scRNA-seq showed that the proportion of T cells, especially the CD4+ T cells, was decreased in SCPs and MPs compared with those in HCs. Transcriptomic results revealed that histone-related genes, and inflammatory genes, such as NFKBIA, S100A9, and PIK3R1, were highly expressed in the total T cells, CD4+ T and CD8+ T cells, both in the cases of SCPs and MPs. In the CD4+ T cells, decreased T helper-1 (Th1) cells were observed in SCPs and MPs. In the CD8+T cells, activation markers, such as CD69 and HLA class II genes (HLA-DRA, HLA-DRB1, and HLA-DRB5), were significantly upregulated in SCPs. An integrated analysis of the data from scATAC-seq and scRNA-seq showed some consistency between the approaches. Cumulatively, we have generated a landscape of chromatin epigenetic status and transcriptomic immune profiles of T cells in patients with COVID-19. This has provided a deeper dissection of the characteristics of the T cells involved at a higher resolution than from previously obtained data merely by the scRNA-seq analysis. Our data led us to suggest that the T-cell inflammatory states accompanied with defective functions in the CD4+ T cells of SCPs may be the key factors for determining the pathogenesis of and recovery from COVID-19.


Subject(s)
CD4-Positive T-Lymphocytes/physiology , CD8-Positive T-Lymphocytes/physiology , COVID-19/immunology , Chromatin/metabolism , SARS-CoV-2/physiology , COVID-19/genetics , Calgranulin B/genetics , Chromatin/genetics , Class Ia Phosphatidylinositol 3-Kinase/genetics , Epigenome/immunology , Gene Expression Profiling , Humans , Immunity, Cellular/genetics , Inflammation/genetics , Lymphocyte Activation , NF-KappaB Inhibitor alpha/genetics , Sequence Analysis, RNA , Single-Cell Analysis , Transposases/metabolism , Up-Regulation
7.
BMJ ; 372: n526, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1112324

ABSTRACT

CLINICAL QUESTION: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. RECOMMENDATION: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). HOW THIS GUIDELINE WAS CREATED: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. UNDERSTANDING THE NEW RECOMMENDATION: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. UPDATES: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. READERS NOTE: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.


Subject(s)
COVID-19/prevention & control , Chemoprevention , Hydroxychloroquine/pharmacology , Risk Assessment , COVID-19/epidemiology , Chemoprevention/methods , Chemoprevention/standards , Clinical Decision-Making/methods , Humans , Immunologic Factors/pharmacology , SARS-CoV-2/drug effects , Uncertainty , World Health Organization
8.
J Infect Dis ; 223(4): 568-580, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1101847

ABSTRACT

BACKGROUND: The immune protective mechanisms during severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection remain to be deciphered for the development of an effective intervention approach. METHODS: We examined early responses of interleukin 37 (IL-37), a powerful anti-inflammatory cytokine, in 254 SARS-CoV-2-infected patients before any clinical intervention and determined its correlation with clinical prognosis. RESULTS: Our results demonstrated that SARS-CoV-2 infection causes elevation of plasma IL-37. Higher early IL-37 responses were correlated with earlier viral RNA negative conversion, chest computed tomographic improvement, and cough relief, consequently resulted in earlier hospital discharge. Further assays showed that higher IL-37 was associated with lower interleukin 6 and interleukin 8 (IL-8) and higher interferon α responses and facilitated biochemical homeostasis. Low IL-37 responses predicted severe clinical prognosis in combination with IL-8 and C-reactive protein. In addition, we observed that IL-37 administration was able to attenuate lung inflammation and alleviate respiratory tissue damage in human angiotensin-converting enzyme 2-transgenic mice infected with SARS-CoV-2. CONCLUSIONS: Overall, we found that IL-37 plays a protective role by antagonizing inflammatory responses while retaining type I interferon, thereby maintaining the functionalities of vital organs. IL-37, IL-8, and C-reactive protein might be formulated as a precise prediction model for screening severe clinical cases and have good value in clinical practice.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/virology , Interleukin-1/blood , Adult , Animals , C-Reactive Protein/metabolism , COVID-19/blood , Female , Humans , Inflammation/immunology , Inflammation/virology , Interleukin-8/blood , Male , Mice , Mice, Transgenic , Middle Aged
9.
Ann Transl Med ; 9(2): 100, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1079877

ABSTRACT

BACKGROUND: To investigate the temporal pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence on ocular surfaces using conjunctival swabs in coronavirus disease 2019 (COVID-19) patients. METHODS: This study included 59 patients (32 newly admitted and 27 hospitalized for ≥2 weeks) with a COVID-19-confirmed diagnosis at the Shanghai Public Health Clinical Center from March 3, 2020, to March 21, 2020. Conjunctival swab samples were collected from both eyes of all the 59 patients and were tested by reverse transcription polymerase chain reaction (RT-PCR) assay. The range of sampling time lies widely between 1 and 50 days since symptom onset. RESULTS: Among the 32 newly admitted patients, positive RT-PCR results for SARS-CoV-2 in conjunctival swab samples were reported in 2 patients (one eye for each) without ocular discomfort, but 1 positive case had conjunctival congestion. The positive results were detected on Day 5 for 1 patient and Day 7 for the other, but repeated tests after 1 week were negative for both patients. All 27 patients who had been hospitalized for ≥2 weeks had negative test results. The mean time from symptom onset to sampling of 2 positive cases was significantly less than that of 57 negative cases (P<0.001). CONCLUSIONS: SARS-CoV-2 on the ocular surface can be detected in the early phase of COVID-19. The risk of ocular transmission remains and might be higher in the early phase.

11.
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 , COVID-19 , 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
12.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 2020.
Article | WHO COVID | ID: covidwho-242643

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with moderate coronavirus disease 2019 (COVID-19). METHODS: We prospectively enrolled 30 treatment-naive patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 11 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only. The primary endpoint was negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization. This study has been approved by the Ethics Committee of Shanghai Public Health Clinical Center and registered online (NCT04261517). RESULTS: One patient in HCQ group developed to severe during the treatment. On day 7, nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P>0.05). The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1,9) days in HCQ group, which is comparable to that in the control group [2 (1,4) days, Z=1.27, P>0.05]. The median time for body temperature normalization in HCQ group was 1 (0,2) day after hospitalization, which was also comparable to that in the control group [1 (0,3) day]. Radiological progression was shown on CT images in 5 cases (33.3%) of the HCQ group and 7 cases (46.7%) of the control group, and all patients showed improvement in follow-up examinations. Four cases (26.7%) of the HCQ group and 3 cases (20%) of the control group had transient diarrhea and abnormal liver function (P>0.05). CONCLUSIONS: The prognosis of COVID-19 moderate patients is good. Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size.

13.
J Infect ; 80(5): e1-e6, 2020 05.
Article in English | MEDLINE | ID: covidwho-7451

ABSTRACT

BACKGROUND: Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19. METHODS: In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020. RESULTS: Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2-7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12-20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8-11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10-12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission. CONCLUSIONS: The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.


Subject(s)
Coronavirus Infections/pathology , Disease Progression , Pneumonia, Viral/pathology , Adult , Betacoronavirus , COVID-19 , China , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Female , Fever/etiology , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Prognosis , Retrospective Studies , SARS-CoV-2 , Time Factors , Tomography, X-Ray Computed
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