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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323932

ABSTRACT

Background: Patients with severe Coronavirus Disease 2019 (COVID-19) will progress rapidly to acute respiratory failure or death. We aimed to develop a quantitative tool for early predicting mortality risk of patients with COVID-19. Methods: : 301 patients with confirmed COVID-19 admitted to Main District and Tumor Center of the Union Hospital of Huazhong University of Science and Technology (Wuhan, China) between January 1, 2020 to February 15, 2020 were enrolled in this retrospective two-centers study. Data on patient demographic characteristics, laboratory findings and clinical outcomes was analyzed. A nomogram was constructed to predict the death probability of COVID-19 patients. Results: : Age, neutrophil-to-lymphocyte ratio, D-dimer and C-reactive protein obtained on admission were identified by LASSO regression as predictors of mortality for COVID-19 patients. The nomogram demonstrated good calibration and discrimination with the area under the curve (AUC) of 0.921 and 0.975 for the derivation and validation cohort, respectively. An integrated score (named ANDC) with its corresponding death probability was derived. Using ANDC cut-off values of 59 and 101, COVID-19 patients were classified into three subgroups. The death probability of low risk group (ANDC < 59) was less than 5%, moderate risk group (59 ≤ ANDC ≤ 101) was 5% to 50%, and high risk group (ANDC > 101) was more than 50%, respectively. Conclusion: The prognostic nomogram exhibited good discrimination power in early identification of COVID-19 patients with high mortality risk, and ANDC score may help physicians to optimize patient stratification management.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315379

ABSTRACT

Background: While the immunogenicity of inactivated vaccines against coronavirus disease 2019 (COVID‐19) has been characterized in several well-conducted clinical trials, real-world evidence concerning immune responses against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) raised by such vaccines is currently missing. Here, we comprehensively characterized various parameters of SARS-CoV-2-specific cellular and humoral immune responses induced by inactivated COVID-19 vaccines under real-world conditions. Methods: Venous blood was collected from 126 adults, before and/or after inactivated COVID-19 vaccine inoculation. SARS-CoV-2 neutralizing antibody (NAb) and S-receptor binding domain IgG in the serum were detected. The isolated peripheral blood mononuclear cells were stimulated by three pools of lyophilized peptides covering the spike, nucleocapsid, and membrane protein of SARS-CoV-2 for evaluating antigen-specific T cell responses against the virus. Findings: The seroconversion rate for S-RBD IgG and NAb after two doses of vaccination was 87.06% (74/85) and 78.82% (67/85), respectively. Female participants developed higher concentrations of S-RBD IgG and NAb compared to male vaccinees. Interestingly, a longer dosing interval between the first and second vaccination resulted in a better long-term SARS-CoV-2 S-RBD IgG response. The frequencies of CD4+ T cells that produce effector cytokines (IFN-γ, IL-2, and TNF-α) in response to stimulation with peptide pools corresponding to the SARS-CoV-2 spike (S), nucleocapsid (N) or membrane (M) protein increased significantly after a single vaccination dose, and continued to increase after the second administration. S, N, or M-specific CD4+ and CD8+ T cell responses became detectable in 95.83% (69/72) and 54.16% (39/72) of double-vaccinated individuals, respectively. The longitudinal analysis demonstrated that CD4+ T cell responses recognizing S, N, and M waned quickly after a single vaccine dose, but were boosted and became more sustained following a second dose. Interpretation: Both humoral and cellular SARS-CoV-2-specific immunity are elicited in the majority of individuals after two doses of inactivated COVID-19 vaccines. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100048837).Funding Fundamental Research Funds for the Central Universities, National Natural Science Foundation of China, National Science and Technology Major Project, Deutsche Forschungsgemeinschaft, Medical Faculty of the University of Duisburg-Essen and Stiftung Universiätsmedizin, University Hospital Essen, Germany, and the Tongji-Rongcheng Center for Biomedicine, Huazhong University of Science and Technology.Declaration of Interest: None to declare. Ethical Approval: The study protocol was approved by the local medical ethics committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (2021-0570)

3.
Frontiers in immunology ; 12, 2021.
Article in English | EuropePMC | ID: covidwho-1602189

ABSTRACT

While the immunogenicity of inactivated vaccines against coronavirus disease 2019 (COVID‐19) has been characterized in several well-conducted clinical trials, real-world evidence concerning immune responses against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) raised by such vaccines is currently missing. Here, we comprehensively characterized various parameters of SARS-CoV-2-specific cellular and humoral immune responses induced by inactivated COVID-19 vaccines in 126 individuals under real-world conditions. After two doses of vaccination, S-receptor binding domain IgG (S-RBD IgG) and neutralizing antibody (NAb) were detected in 87.06% (74/85) and 78.82% (67/85) of individuals, respectively. Female participants developed higher concentrations of S-RBD IgG and NAb compared to male vaccinees. Interestingly, a longer dosing interval between the first and second vaccination resulted in a better long-term SARS-CoV-2 S-RBD IgG response. The frequencies of CD4+ T cells that produce effector cytokines (IFN-γ, IL-2, and TNF-α) in response to stimulation with peptide pools corresponding to the SARS-CoV-2 spike (S), nucleocapsid (N) or membrane (M) protein were significantly higher in individuals received two doses of vaccine than those received one dose of vaccine and unvaccinated individuals. S, N, or M-specific CD4+ and CD8+ T cell responses were detectable in 95.83% (69/72) and 54.16% (39/72) of double-vaccinated individuals, respectively. The longitudinal analysis demonstrated that CD4+ T cell responses recognizing S, N, and M waned quickly after a single vaccine dose, but were boosted and became more sustained following a second dose. Overall, we provide a comprehensive characterization of immune responses induced by inactivated COVID-19 vaccines in real-world settings, suggesting that both humoral and cellular SARS-CoV-2-specific immunity are elicited in the majority of individuals after two doses of inactivated COVID-19 vaccines.

4.
Ann Med ; 53(1): 181-188, 2021 12.
Article in English | MEDLINE | ID: covidwho-1575964

ABSTRACT

OBJECTIVE: To illustrate the effect of corticosteroids and heparin, respectively, on coronavirus disease 2019 (COVID-19) patients' CD8+ T cells and D-dimer. METHODS: In this retrospective cohort study involving 866 participants diagnosed with COVID-19, patients were grouped by severity. Generalized additive models were established to explore the time-course association of representative parameters of coagulation, inflammation and immunity. Segmented regression was performed to examine the influence of corticosteroids and heparin upon CD8+ T cell and D-dimer, respectively. RESULTS: There were 541 moderate, 169 severe and 156 critically ill patients involved in the study. Synchronous changes of levels of NLR, D-dimer and CD8+ T cell in critically ill patients were observed. Administration of methylprednisolone before 14 DFS compared with those after 14 DFS (ß = 0.154%, 95% CI=(0, 0.302), p=.048) or a dose lower than 40 mg per day compared with those equals to 40 mg per day (ß = 0.163%, 95% CI=(0.027, 0.295), p=.020) significantly increased the rising rate of CD8+ T cell in 14-56 DFS. CONCLUSIONS: The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.


Subject(s)
CD8-Positive T-Lymphocytes/drug effects , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Inflammation/drug therapy , Adult , Aged , Aged, 80 and over , Blood Coagulation/drug effects , Blood Coagulation/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Dose-Response Relationship, Drug , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/immunology , Heparin/administration & dosage , Humans , Inflammation/blood , Inflammation/diagnosis , Inflammation/immunology , Linear Models , Longitudinal Studies , Lymphocyte Count , Male , Methylprednisolone/administration & dosage , Middle Aged , Models, Biological , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Time Factors , Time-to-Treatment , Young Adult
5.
Disaster Med Public Health Prep ; : 1-8, 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1531950

ABSTRACT

BACKGROUND: The unprecedented disruption brought about by the global coronavirus disease 2019 (COVID-19) pandemic had produced tremendous influence on the practice of pharmacy. Sufficient knowledge of pharmacists was needed to deal with the epidemic situation; however, outbreak also aggravated psychological distress among health-care professionals. Therefore, this study aimed to determine knowledge about the pandemic and related factors, prevalence and factors associated with psychological distress among hospital pharmacists of Xinjiang Province, China. METHODS: An anonymous online questionnaire-based cross-sectional study was conducted by means of WeChat, a popular social media platform in China, February 23-27, 2020, during the COVID-19 outbreak. The survey questionnaire consisted of 4 parts, including informed consent section, demographic section, knowledge about COVID-19, and assessment of overall mental health through World Health Organization's Self-Reporting Questionnaire (SRQ-20). A score of 8 or above on SRQ-20 was used as cutoff to classify the participant as in psychological distress. SRQ-20 score and related knowledge score were used as dependent variables, demographic characteristics (such as gender, age, monthly income, etc.) were used as independent variables, and univariate binary logistic regression was used to screen out the variables with P < 0.05. Then, the filtered variables were used as independent variables, and multivariate logistic regression models were used to analyze associations with sufficient knowledge of COVID-19 and psychological distress. RESULTS: A total of 365 pharmacists participated in the survey, fewer than half (35.1%; n = 128) of pharmacists attained a score of 6 or greater (out of 10) in overall disease knowledge, and most were able to select effective disinfectants and isolation or discharge criteria. In the multivariable model, age ages 31-40 (odds ratio [OR] = 3.25; P < 0.05), ages 41-50 (OR = 2.96; P < 0.05) versus >50 (referent); primary place of practice in hospitals: drug supply (OR = 4.00; P < 0.01), inpatient pharmacy (OR = 2.06, P < 0.01), clinical pharmacy (OR = 2.17, P < 0.05) versus outpatient pharmacy (referent); monthly income Renminbi (RMB, China's legal currency) 5000-10,000 (OR = 1.77; P < 0.05) versus < 5000 (referent); contact with COVID-19 patients or suspected cases (OR = 2.27; P < 0.01); access to COVID-19 knowledge remote work+ on-site work (OR = 6.07; P < 0.05), single on-site work (OR = 6.90; P < 0.01) versus remote work (referent) were related to better knowledge of COVID-19. Research found that 18.4% of pharmacists surveyed met the SRQ-20 threshold for distress. Self-reported history of mental illness (OR = 3.56; P < 0.05) and working and living in hospital versus delay in work resumption (OR = 2.87; P < 0.01) were found to be risk factors of psychological distress. CONCLUSIONS: Further training of COVID-19 knowledge was required for pharmacists. As specific pharmacist groups were prone to psychological distress, it was important for individual hospitals and government to consider and identify pharmacists' needs and take steps to meet their needs with regard to pandemic and other work-related distress.

7.
Front Immunol ; 12: 722027, 2021.
Article in English | MEDLINE | ID: covidwho-1399138

ABSTRACT

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals who mounted a detectable antibody response with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients did. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections.


Subject(s)
Antibodies, Viral/blood , Asymptomatic Infections/epidemiology , COVID-19/immunology , Immunity, Humoral , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibody Formation , COVID-19/epidemiology , China , Epidemiological Monitoring , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/pathogenicity , Young Adult
8.
Chinese Journal of Viral Diseases ; 11(2):156-160, 2021.
Article in Chinese | GIM | ID: covidwho-1310265

ABSTRACT

In the face of the sudden outbreak of novel coronavirus pneumonia (coronavirusdisease-19, COVID-19), the research and development of new antiviral drugs requires a certain amount of time and cost, and it is urgent to find safe and effective antiviral drugs that can be used clinically. Lopinavir/ritonavir (lopinavir/ritonavir, LPV/r) is a commonly used antiviral drug against adult or child human immunodeficiency virus (humanimmunodeficiency, HIV) infections. Past animal trials and clinical experience suggest It is expected to have a certain anti-viral efficacy against the new coronavirus in the fight against severe acute respiratory syndrome (Severe acute respiratory syndrome, SARS) and Middle East respiratory syndrome (Midle East respiratory syndrome, MERS). drug. Especially for patients with mild infections, the combination of drugs seems to be expected to exert a better effect, but it is necessary to pay attention to the issue of drug safety and use drugs with caution. This article aims to review the clinical research progress of LPV/r anti-coronavirus infection treatment for clinical reference.

9.
Front Immunol ; 12: 708523, 2021.
Article in English | MEDLINE | ID: covidwho-1295646

ABSTRACT

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Aged , Antibody Formation/immunology , COVID-19/therapy , Convalescence , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Male , Middle Aged , Phosphoproteins/immunology , Spike Glycoprotein, Coronavirus/immunology , Time Factors
11.
J Clin Transl Hepatol ; 9(2): 269-273, 2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1234939

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide. We report here two cases of chronic hepatitis B patients with acute respiratory syndrome coronavirus 2 infection treated with tenofovir disoproxil fumarate who demonstrated a favorable outcome. This report adds some evidence that concurrent HBV infection may not worsen COVID-19 infection and tenofovir disoproxil fumarate treatment may have partial positive effect on COVID-19 rapid recovery.

12.
mBio ; 12(2)2021 04 27.
Article in English | MEDLINE | ID: covidwho-1206004

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected over 120 million people and killed over 2.7 million individuals by March 2021. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remain to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19-convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2-unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of annexin V and 7-aminoactinomycin D (7-AAD) double-positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies and TIM-3 expression on CD4 and CD8 T cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by granzyme B (GzmB) expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully able to proliferate and produce effector cytokines upon T cell receptor (TCR) stimulation. Collectively, we provide a comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease.IMPORTANCE Wuhan was the very first city hit by SARS-CoV-2. Accordingly, the patients who experienced the longest phase of convalescence following COVID-19 reside here. This enabled us to investigate the "immunological scar" left by SARS-CoV-2 on cellular immunity after recovery from the disease. In this study, we characterized the long-term impact of SARS-CoV-2 infection on the immune system and provide a comprehensive picture of cellular immunity of a convalescent COVID-19 patient cohort with the longest recovery time. We revealed that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease; in particular, a profound NKT cell impairment was found in the convalescent phase of COVID-19.


Subject(s)
COVID-19/immunology , Convalescence , Immunity, Cellular , Natural Killer T-Cells/immunology , Adult , Apoptosis , COVID-19/diagnosis , Cohort Studies , Cytokines/immunology , Cytotoxicity, Immunologic , Female , Humans , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Phenotype , SARS-CoV-2/immunology , T-Lymphocyte Subsets/immunology
13.
Nat Commun ; 12(1): 1813, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1147224

ABSTRACT

Long-term antibody responses and neutralizing activities in response to SARS-CoV-2 infection are not yet clear. Here we quantify immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of 6 months from COVID-19 disease onset in 349 symptomatic COVID-19 patients who were among the first be infected world-wide. The positivity rate and magnitude of IgM-S and IgG-N responses increase rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset are associated with virus control and IgG-S titers correlate closely with the capacity to neutralize SARS-CoV-2. Although specific IgM-S/N become undetectable 12 weeks after disease onset in most patients, IgG-S/N titers have an intermediate contraction phase, but stabilize at relatively high levels over the 6 month observation period. At late time points, the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies are still >70%. These data indicate sustained humoral immunity in recovered patients who had symptomatic COVID-19, suggesting prolonged immunity.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Female , Humans , Immunity, Humoral/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Middle Aged , Severity of Illness Index , Spike Glycoprotein, Coronavirus
14.
Front Med ; 15(3): 486-494, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1122810

ABSTRACT

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.


Subject(s)
COVID-19 , Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , Humans , SARS-CoV-2 , Treatment Outcome
15.
Virol Sin ; 35(6): 673-684, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1044644

ABSTRACT

The recent emergence and rapid global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose an unprecedented medical and socioeconomic crisis, and the disease caused by it, Coronavirus disease 2019 (COVID-19), was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Chinese scientists and physicians rapidly identified the causative pathogen, which turned out to be a novel betacoronavirus with high sequence similarities to bat and pangolin coronaviruses. The scientific community has ignited tremendous efforts to unravel the biological underpinning of SARS-CoV-2, which constitutes the foundation for therapy and vaccine development strategies. Here, we summarize the current state of knowledge on the genome, structure, receptor, and origin of SARS-CoV-2.


Subject(s)
COVID-19/virology , Receptors, Virus/metabolism , SARS-CoV-2/physiology , Animals , Betacoronavirus/genetics , Genome, Viral , Humans , Pandemics , Receptors, Virus/genetics , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , World Health Organization
16.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-5138

ABSTRACT

Background: Tocilizumab is reported to be able to attenuate the "cytokine storm" in COVID-19 patients. We tried to ascertain the effectiveness and safety of tocilizumab in COVID-19 and identify patients most likely to be benefit from the treatment. Methods: This was a randomized, controlled, open-label, multicenter trial at 6 hospitals in Anhui and Hubei. Patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care, or standard care alone. The first dose of tocilizumab was 400 mg, diluted in 100 ml 0.9% saline, and intravenous dripped in more than 1 h. A second dose was given if a patient remained febrile for 24 hours after the first dose. The primary endpoint was the cure rate. Primary analysis was done in the intention -to -treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. Findings: Between Feb 13, 2020, and March 13, 2020, 65 patients were enrolled and randomly assigned to a treatment group (33 to tocilizumab and 32 to the controls). One patient in the control group, who aggravated severely 3 days after randomization, was transferred to the tocilizumab group. The cure rate in tocilizumab group was higher than that in the controls but not significant (94.12% vs 87.10%, P=0.4133). Adverse events were recorded in 20 (58.82%) of 34 tocilizumab recipients versus 4 (12.90%) of 31 in the controls. No serious adverse events were reported in tocilizumab group. Interpretation: Tocilizumab treatment did not increase the cure rate of COVID-19. A large scale of study enrolling more patients is needed. However,tocilizumab can improve oxygenation without significant influence on the time virus load tunes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab should be recommended for better disease management. Trial Registration: This trial was registered in Chinese Clinical Trial Registry (Number: ChiCTR2000029765). Funding: This work was supported by Department of Science and Technology of Anhui Province and Health Commission of Anhui Province (grant number: 202004a07020001) and the China National Center for Biotechnology Development (grant number: 2020YFC0843800).

17.
mBio ; 11(5), 2020.
Article in English | GIM | ID: covidwho-913692

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8<sup>+</sup> T cells, but not CD4<sup>+</sup> T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8<sup>+</sup> T cell subsets. PD-1- expressing CD8<sup>+</sup> T cells also produced cytotoxic molecules during acute infection, indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years, the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8<sup>+</sup> cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provide valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development. IMPORTANCE Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8<sup>+</sup> T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8<sup>+</sup> T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8<sup>+</sup> T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group than in younger patients.

18.
Eur J Med Res ; 25(1): 54, 2020 Nov 04.
Article in English | MEDLINE | ID: covidwho-910324

ABSTRACT

BACKGROUND: The novel coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading to a worldwide pandemic. Except representative manifestation of pneumonia and acute respiratory symptoms, COVID-19 patients have also shown different levels of liver injury or liver dysfunction. The aim of our study was to explore the probable clinical severity and mortality of COVID-19 patients and their liver dysfunction. METHOD: A combination of computer and manual retrieval was used to search in Medline through PubMed, EMBASE and Web of Science. Review Manager 5.3 software was used to examine the heterogeneity among the studies and to calculate the combined effect value (OR, 95CI). Subgroup analysis, sensitivity analysis, and publication bias test were also performed. RESULTS: We found a significant connection between liver dysfunction and mortality of COVID-19 patients with a pooled OR of 1.98 (95% CI 1.39-2.82; P = 0.0002). There was a significant association between AST and severity of COVID-19 with a pooled OR of 4.48 (95% CI 3.24-7.21; P < 0.001), and a pooled WMD of 3.35 (95% CI, 2.07 to 4.64; P < 0.001). In addition, there was a significant difference between TBIL and severity of COVID-19, with a pooled OR of 1.91 (95% CI 1.40-2.60; P < 0.001), and with a pooled WMD of 1.18 (95% CI, 0.78 to 1.58; P < 0.001). CONCLUSION: The mortality and severity of COVID-19 patients are significantly associated with liver dysfunction. The non-survivors and severe COVID-19 patients have elevated serum AST levels than the survivors and non-severe COVID-19 patients. The results of this study form a basis for better clinical liver management of patients with COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Liver Diseases/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , Comorbidity , Global Health , Humans , SARS-CoV-2 , Survival Rate/trends
19.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-613

ABSTRACT

Background: Chest CT image guided handling of pneumonia patients with negative RT-PCR detection of SARS-CoV-2 in high endemic areas is still controversial. b

20.
mBio ; 11(5)2020 09 18.
Article in English | MEDLINE | ID: covidwho-781095

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8+ T cell subsets. PD-1-expressing CD8+ T cells also produced cytotoxic molecules during acute infection, indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years, the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provide valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development.IMPORTANCE Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group than in younger patients.


Subject(s)
CD8-Positive T-Lymphocytes/pathology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , T-Lymphocytes, Cytotoxic/pathology , Aged, 80 and over , Antigens, CD/metabolism , Betacoronavirus/pathogenicity , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Cytotoxins/metabolism , Female , Humans , Immunity, Cellular , Male , Middle Aged , Pandemics , SARS-CoV-2 , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/pathology , T-Lymphocytes, Cytotoxic/immunology
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