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1.
Mol Cell ; 2021 Apr 13.
Article in English | MEDLINE | ID: covidwho-1179919

ABSTRACT

A deficient interferon (IFN) response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated as a determinant of severe coronavirus disease 2019 (COVID-19). To identify the molecular effectors that govern IFN control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human IFN-stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of endoplasmic reticulum (ER)/Golgi-resident ISGs inhibiting viral assembly/egress. These included broad-acting antiviral ISGs and eight ISGs that specifically inhibited SARS-CoV-2 and SARS-CoV-1 replication. Among the broad-acting ISGs was BST2/tetherin, which impeded viral release and is antagonized by SARS-CoV-2 Orf7a protein. Overall, these data illuminate a set of ISGs that underlie innate immune control of SARS-CoV-2/SARS-CoV-1 infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19.

2.
Front Immunol ; 12: 671443, 2021.
Article in English | MEDLINE | ID: covidwho-1172967

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2021.627844/full.].

3.
Front Immunol ; 12: 627844, 2021.
Article in English | MEDLINE | ID: covidwho-1121106

ABSTRACT

Background: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. Methods: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. Results: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. Conclusions: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.


Subject(s)
/drug therapy , Immunoglobulins, Intravenous/administration & dosage , /metabolism , Adult , Aged , China/epidemiology , Disease-Free Survival , Female , Ferritins/blood , Humans , Interleukin-10/blood , Interleukin-6/blood , Male , Middle Aged , Retrospective Studies , Survival Rate
4.
Mol Cell ; 2020 Oct 29.
Article in English | MEDLINE | ID: covidwho-1009762

ABSTRACT

The causative virus of the COVID-19 pandemic, SARS-CoV-2, uses its nonstructural protein 1 (Nsp1) to suppress cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here that among all viral proteins, Nsp1 has the largest impact on host viability in the cells of human lung origin. Differential expression analysis of mRNA-seq data revealed that Nsp1 broadly alters the cellular transcriptome. Our cryo-EM structure of the Nsp1-40S ribosome complex shows that Nsp1 inhibits translation by plugging the mRNA entry channel of the 40S. We also determined the structure of the 48S preinitiation complex formed by Nsp1, 40S, and the cricket paralysis virus internal ribosome entry site (IRES) RNA, which shows that it is nonfunctional because of the incorrect position of the mRNA 3' region. Our results elucidate the mechanism of host translation inhibition by SARS-CoV-2 and advance understanding of the impacts from a major pathogenicity factor of SARS-CoV-2.

6.
Eur J Gastroenterol Hepatol ; 2020 Oct 29.
Article in English | MEDLINE | ID: covidwho-900650

ABSTRACT

BACKGROUND: Liver injury in coronavirus disease 2019 (COVID-19) patients was poorly understood. METHODS: The markers of liver injury, severity of disease and prognosis among 495 COVID-19 patients in Zhongnan Hospital of Wuhan University from 1st January 2019 to 11th March 2019 were retrospectively analyzed. RESULTS: The levels of aspartate aminotransferase (AST) (50.1 ± 38.4 vs. 31.4 ± 39.1, P < 0.001), gamma-glutamyl transpeptidase (GGT) (70.3 ± 70.2 vs. 34.1 ± 34.7, P < 0.001) and fibrinogen-to-albumin-ratio (FAR) (13.4 ± 4.0 vs. 10.4 ± 3.4, P < 0.001) were greater than mild COVID-19 patients, whereas the levels of albumin(35.0 ± 6.2 vs. 39.9 ± 3.7, P < 0.001) and albumin/globulin (A/G) ratio (1.21 ± 0.24 vs. 1.50 ± 0.31, P < 0.001) were lower in severe COVID-19 patients. By comparing the changes of liver injury markers 7-10 days after hospitalization, the level of albumin deteriorated from 35.0 ± 6.2 to 30.20 ± 5.5 (P < 0.001), A/G ratio from 1.21 ± 0.24 to 1.06 ± 0.25 (P < 0.001), and FAR from 13.4 ± 4.0 to 15.4 ± 2.9(P < 0.001) in severe COVID-19 patients, while the changes of albumin, A/G ratio and FAR showed opposite patterns in mild COVID-19 patients. FAR > 12 [2.566 (1.410-4.670), P = 0.012) on admission and changes of albumin >5g/l [22.489 (6.422-78.757), P = 0.001] were two risk factors for death, and the sensitivity and specificity for the poor prognosis were 80.8% and 64.0%, 82.6% and 76.3%, respectively. CONCLUSION: The levels of AST, GGT, albumin and FAR are correlated with disease severity after severe acute respiratory syndrome coronavirus-2 infection. FAR > 12 on admission and changes of albumin > 5 g/l were good predictors for the prognosis of COVID-19 patients.

7.
Expert Rev Respir Med ; : 1-7, 2020 Nov 02.
Article in English | MEDLINE | ID: covidwho-900286

ABSTRACT

OBJECTIVES: To analyze characteristics of asymptomatic/pres-ymptomatic patients with SARS-CoV-2 infection. METHODS: Chest computed tomography(CT), indicators for organ and coagulation function, inflammation cytokines, of asymptomatic/pre-symptomatic patients with SARS-CoV-2 infection were retrospectively analyzed in Zhongnan Hospital of Wuhan University from 20 December 2019, to 8 March 2020. RESULTS: The proportion of normal chest CT in asymptomatic and pre-symptomatic patients with SARS-CoV-2 infection were 35.4% (17/48) and 3.3%(2/61), respectively (P< 0.001). In 17 asymptomatic patients, their images of chest CT maintained normal during the whole course of diseases, while the normal images of chest CT in 2 pre-symptomatic patients progressed to abnormal later (P< 0.001). All the six asymptomatic patients with SARS-CoV-2 infection maintained unilateral lesion, while the proportion was 29.4%(5/17) in pre-symptomatic patients(P= 0.003). Compared with asymptomatic patients, pre-symptomatic COVID-19 patients had worse levels of Lymphocyte count (P= 0.001), Albumin (P= 0.045), Aspartate aminotransferase (P= 0.044), γ-glutamyl transpeptadase (P= 0.016), Globulin (P= 0.036), Creatinine (P= 0.021), Lactate dehydrogenase (P= 0.008), C-reactive protein (P< 0.001), Serum amyloid A (P< 0.001), and Erythrocyte sedimentation rate (P< 0.001). Except for above indicators, Alkaline phosphatase (P= 0.009), Procalcitonin (P= 0.010), and D-dimer(P< 0.001) increased further during periods of symptoms compared with those levels in pre-symptomatic period. CONCLUSION: In early stage after SARS-CoV-2 infection, images of chest CT and blood tests of asymptomatic patients were different from pre-symptomatic patients.

8.
Expert Rev Respir Med ; : 1-7, 2020 Oct 27.
Article in English | MEDLINE | ID: covidwho-872888

ABSTRACT

BACKGROUND: Information about the impact of HIV coinfection on clinical characteristics of COVID-19 patients remains limited. METHODS: Maximum body temperatures, fever duration, chest CT and viral shedding, lymphocyte counts, and titer of SARS-CoV-2 antibody were compared between COVID-19 patients with and without HIV infection in Zhongnan Hospital of Wuhan University from January 20th to February 14th, 2020. RESULTS: Compared with 53 COVID-19 patients without HIV infection, the patients with SARS-CoV-2 and HIV coinfection had higher maximum body temperatures (38.7°C vs 37.6°C, P = 0.044), longer duration of fever (8.7 ± 4.5 vs 4.2 ± 2.1 days, P = 0.038), longer time to have improvement of chest CT images (22 vs 15 days from the onset of illness, P = 0.011), lower level of SARS-CoV-2 IgG (5.11 ± 32.33 vs 37.45 ± 15.48 AU/ml, P = 0.042). However, no statistically significant difference of duration of SARS-CoV-2 shedding in the two groups was found (12.3 ± 2.6 vs 13.4 ± 2.4 days, , P = 0.813). CONCLUSION: Lower level of CD4+ T lymphocyte counts caused by HIV infection itself might be one of reasons for relatively weak ability to produce SARS-CoV-2 specific antibodies. The effects of anti-HIV drugs in prevention and treatment of COVID-19 appears to be limited.

9.
World J Clin Cases ; 8(19): 4360-4369, 2020 Oct 06.
Article in English | MEDLINE | ID: covidwho-819329

ABSTRACT

BACKGROUND: The global outbreak of human severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection represents an urgent need for readily available, accurate and rapid diagnostic tests. Nucleic acid testing of respiratory tract specimens for SARS-CoV-2 is the current gold standard for diagnosis of coronavirus disease 2019 (COVID-19). However, the diagnostic accuracy of reverse transcription polymerase chain reaction (RT-PCR) tests for detecting SARS-CoV-2 nucleic acid may be lower than optimal. The detection of SARS-CoV-2-specific antibodies should be used as a serological non-invasive tool for the diagnosis and management of SARS-CoV-2 infection. AIM: To investigate the diagnostic value of SARS-CoV-2 IgM/IgG and nucleic acid detection in COVID-19. METHODS: We retrospectively analyzed 652 suspected COVID-19 patients, and 206 non-COVID-19 patients in Wuhan Integrated TCM and Western Medicine Hospital. Data on SARS-CoV-2 nucleic acid tests and serum antibody tests were collected to investigate the diagnostic value of nucleic acid RT-PCR test kits and immunoglobulin (Ig)M/IgG antibody test kits. The χ2 test was used to compare differences between categorical variables. A 95% confidence interval (CI) was provided by the Wilson score method. All analyses were performed with IBM SPSS Statistics version 22.0 (IBM Corp., Armonk, NY, United States). RESULTS: Of the 652 suspected COVID-19 patients, 237 (36.3%) had positive nucleic acid tests, 311 (47.7%) were positive for IgM, and 592 (90.8%) were positive for IgG. There was a significant difference in the positive detection rate between the IgM and IgG test groups (P < 0.001). Using the RT-PCR results as a reference, the specificity, sensitivity, and accuracy of IgM/IgG combined tests for SARS-CoV-2 infection were 98.5%, 95.8%, and 97.1%, respectively. Of the 415 suspected COVID-19 patients with negative nucleic acid test results, 366 had positive IgM/IgG tests with a positive detection rate of 88.2%. CONCLUSION: Our data indicate that serological IgM/IgG antibody combined test had high sensitivity and specificity for the diagnosis of SARS-CoV-2 infection, and can be used in combination with RT-PCR for the diagnosis of SARS-CoV-2 infection.

11.
Preprint | SSRN | ID: ppcovidwho-587

ABSTRACT

Circulating in China and 75 other countries and territories, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public h

14.
J Infect Dis ; 221(11): 1762-1769, 2020 05 11.
Article in English | MEDLINE | ID: covidwho-688308

ABSTRACT

BACKGROUND: In December 2019, novel coronavirus (SARS-CoV-2) pneumonia (COVID-19) was reported in Wuhan and has since rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. METHODS: The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. RESULTS: Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with inflammatory status in COVID-19, especially CD8+ T cells and CD4+/CD8+ ratio. After treatment, 37 patients (67%) showed clinical response, with an increase in CD8+ T cells and B cells. No significant change in any subset was detected in nonresponsive cases. In multivariate analysis, posttreatment decrease in CD8+ T cells and B cells and increase in CD4+/CD8+ ratio were indicated as independent predictors of poor efficacy. CONCLUSIONS: Peripheral lymphocyte subset alteration was associated with clinical characteristics and treatment efficacy of COVID-19. CD8+ T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Lymphocyte Subsets , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Pneumonia/etiology , Pneumonia/physiopathology , Adult , Aged , Betacoronavirus/isolation & purification , China , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Female , Flow Cytometry , Humans , Lymphocyte Count , Lymphocyte Subsets/immunology , Male , Middle Aged , Pandemics , Pneumonia/diagnosis , Pneumonia/therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Prognosis , Treatment Outcome
15.
Cancer Discov ; 10(6): 783-791, 2020 06.
Article in English | MEDLINE | ID: covidwho-631598

ABSTRACT

The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. SIGNIFICANCE: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients.This article is highlighted in the In This Issue feature, p. 747.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Neoplasms , Pneumonia, Viral/therapy , Aged , China/epidemiology , Cohort Studies , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Disease Outbreaks , Female , Humans , Intensive Care Units , Male , Middle Aged , Neoplasms/complications , Neoplasms/pathology , Neoplasms/therapy , Neoplasms/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Respiration, Artificial
16.
Infect Dis Poverty ; 9(1): 82, 2020 Jul 02.
Article in English | MEDLINE | ID: covidwho-621510

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of pneumonia in Wuhan. The virus is highly infectious. Patients with cancer might be susceptible to the viral infection because of the immunosuppressive state cause by therapies on tumors. CASE PRESENTATION: We present the clinical features of four cancer patients who were infected with SARS-CoV-2 in late January of 2020 in our hospital. Cases 1 and 3 were diagnosed as mild and common type of coronavirus disease 2019 (COVID-2019) and survived from the viral infection. They acquired SARS-CoV-2 infection during their staying in hospital under radiotherapy and surgery of the tumors. Cases 2 and 4 suffered from severe type of COVID-19, and Case 2 was dead owning to the advanced age, uncontrolled chronic B cell lymphocytic leukemia and many other underlying diseases. The immunosuppressive state induced by liver transplantation and anti-rejection therapy might contribute to the severity of COVID-19 in Case 4, who suffered from hepatitis B related hepatocellular carcinoma. However, Case 4 was recovered from COVID-19 after a combination therapy against virus, bacteria and fungi, and also respiratory support. Nearly all patients showed a decrease in lymphocytes including total CD3+ T cells, B cells, and natural killer cells after infection of the virus. CONCLUSIONS: The severity of COVID-19 might be influenced by immune system state and underlying diseases in cancer patients. And the treatment of SARS-CoV-2 infection in cancer patients is challenged by the immunosuppressive state of these patients under chemotherapy or surgery.


Subject(s)
Betacoronavirus , Coronavirus Infections , Neoplasms/complications , Pandemics , Pneumonia, Viral , Adult , Aged , China , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/physiopathology , Fatal Outcome , Female , Humans , Immunocompromised Host , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Neoplasms/physiopathology , Neoplasms/therapy , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/physiopathology , Radiography, Thoracic
17.
Int J Surg ; 79: 120-124, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-412451

ABSTRACT

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused great public concern worldwide due to its high rates of infectivity and pathogenicity. The Chinese government responded in a timely manner, alleviated the dilemma, achieved a huge victory and lockdown has now been lifted in Wuhan. However, the outbreak has occurred in more than 200 other countries. Globally, as of 9:56 am CEST on 19 May 2020, there have been 4,696,849 confirmed cases of COVID-19, including 315,131 deaths, reported to Word Health Organization (WHO). The spread of COVID-19 overwhelmed the healthcare systems of many countries and even crashed the fragile healthcare systems of some. Although the situation in each country is different, health workers play a critical role in the fight against COVID-19. In this review, we highlight the status of health worker infections in China and other countries, especially the causes of infection in China and the standardised protocol to protect health workers from the perspective of an anaesthesiologist, in the hope of providing references to reduce medical infections and contain the COVID-19 epidemic.


Subject(s)
Coronavirus Infections/transmission , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pandemics , Pneumonia, Viral/transmission , Asymptomatic Diseases , Betacoronavirus , China/epidemiology , Coronavirus Infections/epidemiology , Humans , Infection Control , Pandemics/prevention & control , Personal Protective Equipment , Pneumonia, Viral/epidemiology
19.
Emerg Microbes Infect ; 9(1): 1175-1179, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-361278

ABSTRACT

Different primers/probes sets have been developed all over the world for the nucleic acid detection of SARS-CoV-2 by quantitative real time polymerase chain reaction (qRT-PCR) as a standard method. In our recent study, we explored the feasibility of droplet digital PCR (ddPCR) for clinical SARS-CoV-2 nucleic acid detection compared with qRT-PCR using the same primer/probe sets issued by Chinese Center for Disease Control and Prevention (CDC) targeting viral ORF1ab or N gene, which showed that ddPCR could largely minimize the false negatives reports resulted by qRT-PCR [Suo T, Liu X, Feng J, et al. ddPCR: a more sensitive and accurate tool for SARS-CoV-2 detection in low viral load specimens. medRxiv [Internet]. 2020;2020.02.29.20029439. Available from: https://medrxiv.org/content/early/2020/03/06/2020.02.29.20029439.abstract]. Here, we further stringently compared the performance of qRT-PCR and ddPCR for 8 primer/probe sets with the same clinical samples and conditions. Results showed that none of 8 primer/probe sets used in qRT-PCR could significantly distinguish true negatives and positives with low viral load (10-4 dilution). Moreover, false positive reports of qRT-PCR with UCDC-N1, N2 and CCDC-N primers/probes sets were observed. In contrast, ddPCR showed significantly better performance in general for low viral load samples compared to qRT-PCR. Remarkably, the background readouts of ddPCR are relatively lower, which could efficiently reduce the production of false positive reports.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Multiplex Polymerase Chain Reaction , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Real-Time Polymerase Chain Reaction , DNA Primers , DNA Probes , Humans , Multiplex Polymerase Chain Reaction/methods , Pandemics , Real-Time Polymerase Chain Reaction/methods , Real-Time Polymerase Chain Reaction/standards , Sensitivity and Specificity , Viral Load
20.
Emerg Microbes Infect ; 9(1): 1259-1268, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-342833

ABSTRACT

Quantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27-55%), 100% (95% CI: 54-100%), 100%, 16% (95% CI: 13-19%), 0.6 (95% CI: 0.48-0.75) and 47% (95% CI: 33-60%) for RT-PCR to 94% (95% CI: 83-99%), 100% (95% CI: 48-100%), 100%, 63% (95% CI: 36-83%), 0.06 (95% CI: 0.02-0.18), and 95% (95% CI: 84-99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5-12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction/methods , False Negative Reactions , Humans , Limit of Detection , Pandemics , RNA, Viral/genetics , Viral Load/methods
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