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2.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2102665

ABSTRACT

Background The aim of this study was to explore the short-term safety and immunogenicity of inactivated and peptide-based SARS-CoV-2 vaccines in patients with endocrine-related cancer (ER). Methods Eighty-eight patients with ER cancer and 82 healthy controls who had completed a full course of inactivated or peptide-based SARS-CoV-2 vaccines were recruited. Adverse events (AEs) were recorded. Responses to receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD+ memory B cells (MBCs) were evaluated. Results Approximately 26.14% (23/88) of patients with ER cancer reported AEs within 7 days, which was comparable to that reported by healthy controls (24.39%, 20/82). Both the overall seroprevalence of anti-RBD-IgG and NAbs was obviously lower in the cancer group (70.45% vs. 86.59%, P < 0.05;69.32% vs. 82.93%, P < 0.05, respectively). Anti-RBD-IgG and NAbs titers exhibited similar results, and dropped gradually over time. Patients with ongoing treatment had an attenuated immune response, especially in patients receiving active chemotherapy. The frequency of overall RBD+ MBCs was similar between the two groups, but the percentage of active MBCs was remarkably reduced in patients with ER cancer. Unlike antibody titers, MBCs responses were relatively constant over time. Conclusion Inactivated and peptide-based COVID-19 vaccines were well tolerated, but with lower immunogenicity for ER cancer patients. More intensive antibody monitoring and timely booster immunization is recommended for patients with ER cancer presenting disordered subpopulations of RBD+ MBCs.

3.
Front Pharmacol ; 13: 978979, 2022.
Article in English | MEDLINE | ID: covidwho-2009899

ABSTRACT

Background: Our previous studies have shown that Yindan Jiedu granules (YDJDG) can effectively treat coronavirus disease 2019 (COVID-19); however, the high infectivity and the immune escape potential of the Omicron variant BA.2 make it more difficult to control, and patients with high-risk factors prone to progress rapidly. Purpose: To evaluate YDJDG's efficacy in treating patients with the Omicron variant BA.2 with high-risk factors and compared it with that of Paxlovid. Methods: A total of 257 patients who fulfilled the inclusion criteria were allocated to the YDJDG (115 cases), Paxlovid (115 cases), and control (27 cases) groups. A Cox regression model was used to analyze the independent factors affecting the shedding time of nucleic acid in 14 days. Propensity score matching (PSM) was used to match the characteristics of individuals in the three groups, while the Kaplan-Meier method was used to compare the shedding proportion of nucleic acids. Results: Cox analysis showed that the vaccine booster (p = 0.006), YDJDG treatment (p = 0.020), and Paxlovid treatment (p < 0.0001) were independent predictors of nucleic acid shedding at 14 days. The median recovery time was 11.49 days in the YDJDG group, 10.21 days in the Paxlovid group, and 13.93 days in the control group. After PSM (3:1), the results showed that the nucleic acid shedding time of the YDJDG group (n = 53) was 2.47 days shorter than that of the control group (n = 21) (p = 0.0076), while the Paxlovid group (n = 44) had a 4.34 days shorter than that of the control group (n = 17) (p < 0.0001). After PSM (1:1), YDJDG and Paxlovid (76 pairs) were also analyzed. In the YDJDG group, nucleic acid shedding time was 1.43 days longer than that observed in the Paxlovid group (p = 0.020). At 10 and 14 days, the Paxlovid group showed a significant difference in the nucleic acid shedding proportion compared with the control group (p = 0.036, p = 0.0015). A significant difference was also observed between the YDJDG and control groups (p = 0.040) at 14 days. Conclusion: As a safe and convenient oral drug, YDJDG can be used as an alternative to antiviral therapy for such patients.

4.
Exp Ther Med ; 24(3): 580, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1988097

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a global pandemic, but treatment options remain limited. Up to now, vaccination has been the main strategy to prevent transmission and reduce disease severity. However, with follow-up observations after massive vaccination, immune thrombocytopenic purpura (ITP) induced by COVID-19 vaccines has attracted the attention of investigators. The present study reported the case of a 78-year-old elderly female who presented with 'oral bleeding for 2 days and scattered bleeding spots on the extremities for 1 day' after vaccination with the COVID-19 vaccine (Vero Cells), and blood routine analysis indicated a white blood cell count of 6.27x109/l, hemoglobin levels of 144 g/l and a low platelet (PLT) count of 1x109/l. Bone marrow cytomorphology showed thrombocytopenia, while no platelet-producing megakaryocytes were observed. The patient was diagnosed with ITP and given symptomatic and supportive treatment, such as prednisone acetate 1 mg/kg, recombinant human thrombopoietin, intravenous injection of human immunoglobulin 0.4 g/kg and prevention of bleeding. At 1 week after the treatment started, the patient's PLT count began to increase, and 9 days later, it returned to normal levels. The aim of the present study was to raise the awareness of medical staff regarding this disease and to increase the vigilance of the general public. At the same time, the present study also provided an effective method to manage this type of adverse reaction to the COVID-19 vaccine.

5.
Scientific Programming ; : 1-10, 2022.
Article in English | Academic Search Complete | ID: covidwho-1986439

ABSTRACT

After the outbreak of the COVID-19 pandemic, cloud computing and voice recognition services have provided a more critical role in the enterprise supply chain management process. Speech emotion recognition technology can identify the content and emotion of the speaker according to the content and tone of speech. Analyzing the attitude and tone behind a statement through language and high-level information acquisition is very difficult. Cloud computing technology is becoming more widely used each day and is the cornerstone of enterprise information development. The anti-globalization caused by COVID-19 has made enterprises pay increasing attention to supply chain management. Determining how to optimize and integrate the supply chain has become an urgent problem for enterprises. Based on the work and research completed in this field, this paper first analyzes the algorithm and model used in speech recognition and then tests the system. To improve the utilization rate of enterprise resources and enterprise industrial benefits, this paper puts forward the optimization scheme of the enterprise supply chain from the perspective infrastructure construction to product development to backstage management and procurement. [ FROM AUTHOR] Copyright of Scientific Programming is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

6.
Acta Veterinaria et Zootechnica Sinica ; 53(4):1173-1181, 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-1975364

ABSTRACT

The purpose of this study is to establish a blocking ELISA antibodies detection method for porcine epidemic diarrhea virus (PEDV). The purified N protein was used as the coating antigen, and the ELISA reaction conditions were optimized by the chess rboard titration. A blocking ELISA method for detecting PEDV antibodies was established, and its specificity, sensitivity and repeatability tests were carried out. One hundred and forty clinical serum samples were tested, and the results were compared with commercially IDvet PEDV indirect ELISA antibodies detection kit. The results showed that the best antigen coating concentration was 625 ng.mL-1, and the best dilution ratio of serum was 1:1;The best dilution of the HRP-conjugated antibody working solution was 1:5 000;There was no cross-reaction with healthy pig serum and the positive sera of common pig disease pathogens, such as classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV2), and transmissible gastroenteritis virus (TGEV). The sensitivity of PEDV positive serum was 1:16, which was equivalent to that of IDvet ELISA kit (titer 1:32). The coefficient of variation of within-run and between-run repeatability test is less than 10%, so it showed that the blocking ELISA established in this study had good repeatability and stability;the kappa value of detected 140 clinical porcine serum using this method was 0.87 when compared with IDvet ELISA. The above results indicated that the established blocking ELISA method for detecting PEDV antibodies in this study could be applied to the prevention and control of PEDV, epidemiological investigation and the monitoring of antibody levels after vaccine immunization.

7.
Vaccines (Basel) ; 10(8)2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1969532

ABSTRACT

This real-world study explores the effect of coronavirus disease 2019 (COVID-19) inactivated vaccines on the prevention of asymptomatic or mild Delta or Omicron variant infections progressing to pneumonia. Association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia cases and vaccination was measured with a multivariable logistic regression, stratified by genotype and age groups. We recruited 265 cases (111 (41.9%) infected with Delta and 154 (58.1%) with Omicron variants). There were 22 asymptomatic infected individuals, 156 mild cases without pneumonia, and 87 moderate cases with pneumonia. There was a markedly increased risk of progression to pneumonia in Delta infected cases, unvaccinated, or partially vaccinated COVID-19 patients with diabetes and those aged ≥60 years. Patients who had completed booster doses of inactivated vaccines had a reduced risk of 81.6% (95% CI: 55.6-92.4%) in progressing to pneumonia over those who were unvaccinated or partially vaccinated. The risk of progressing to pneumonia was less reduced by 88.7% (95% CI: 56.6-97%) and 73.9% (95% CI: 1.4-93.1%) among Delta and Omicron-infected patients, and was reduced by 78.5% (95% CI: 45.3-91.6%) and 94.1% (95% CI: 21.5-99.6%) among patients aged <60 and ≥60 years, respectively. Our data indicated that a complete vaccination with a booster reduced the risk of asymptomatic or mild Delta or Omicron variant COVID-19 progressing to pneumonia and, thus, reduced the pressure of severe illness on medical resources.

8.
Int J Infect Dis ; 122: 874-884, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1956171

ABSTRACT

OBJECTIVES: This study aimed to evaluate the safety and immunogenicity of inactivated COVID-19 vaccines in patients with gastrointestinal cancer (GI) cancer. The role of memory B cells (MBCs) in the humoral response to COVID-19 vaccination was also investigated. METHODS: In this prospective observational study, GI cancer patients and healthy individuals who had received 2 doses of inactivated COVID-19 vaccines were included. The data regarding adverse effects, serum anti-receptor binding domain (RBD)-IgG, neutralizing antibodies (NAbs), and frequencies of MBCs were collected prospectively. RESULTS: The inactivated COVID-19 vaccines were safe and well tolerated. Serum anti-RBG-IgG and NAbs were lower for cancer patients. Old age, high ASA score, and receiving active chemotherapy were risk factors for lower antibody titers. The frequencies of activated and resting MBCs decreased in (17.45% vs 38.11%, P = 0.002; 16.98% vs 34.13%, P = 0.023), while the frequencies of intermediate and atypical MBCs increased in cancer patients (40.06% vs 19.87%, P = 0.010; 25.47% vs 16.61%, P = 0.025). The serum antibody titer decreased gradually during follow-up but increased when a booster vaccine was given. CONCLUSION: The inactivated COVID-19 vaccines were well tolerated in patients with GI cancer but with lower immunogenicity. The subpopulations of MBCs were disordered in cancer patients, and a booster vaccine may be prioritized for them.


Subject(s)
COVID-19 Vaccines , COVID-19 , Gastrointestinal Neoplasms , Humans , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Gastrointestinal Neoplasms/chemically induced , Immunoglobulin G , SARS-CoV-2 , Vaccines, Inactivated/immunology , Immunogenicity, Vaccine
10.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337032

ABSTRACT

ABSTRACT Recent studies found that Omicron variant escapes vaccine-elicited immunity. Interestingly, potent cross-clade pan-sarbecovirus neutralizing antibodies were found in survivors of the infection by SARS-CoV-1 after BNT162b2 mRNA vaccination ( N Engl J Med. 2021 Oct 7;385(15):1401-1406 ). These pan-sarbecovirus neutralizing antibodies were observed to efficiently neutralize the infection driven by the S protein from both SARS-CoV and multiple SARS-CoV-2 variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta). However, whether these cross-reactive antibodies could neutralize the Omicron variant is still unknown. Based on the data collected from a cohort of SARS-CoV-1 survivors received 3-dose of immunization, our studies reported herein showed that a high level of neutralizing antibodies against both SARS-CoV-1 and SARS-CoV-2 were elicited by a 3rd-dose of booster vaccination of protein subunit vaccine ZF2001. However, a dramatically reduced neutralization of SARS-CoV-2 Omicron Variant (B.1.1.529) is observed in sera from these SARS-CoV-1 survivors received 3-dose of Vaccination. Our results indicates that the rapid development of pan-variant adapted vaccines is warranted.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325211

ABSTRACT

Background: Possibility of psychotic symptoms and related risk factors among the normal person and infected patients during the outbreak of COVID-19 has been widely investigated in previous studies. With the arrival of the second wave of the epidemic in many countries around the word, the accordingly mental health outcomes were unclear yet, especially the mental health outcomes among infected patients. It aims to explore the prevalence of and related risk factors associated with psychotic symptoms in COVID-19 infected inpatients during the second wave. Method: A cross-sectional survey was conducted in five isolated wards of a designated hospital in Beijing, China, from 1 July to 15 July, 2020. The Mini-International Neuropsychiatric Interview (M.I.N.I) was conducted to assess the psychiatric disorders, and a serious of scales was used to measure self-reported psychotic symptoms and psychosomatic factors. Multivariate regression analysis was used to analyze the risk factors associated with psychotic symptoms. Results Among 199 infected participants, the prevalence of generalized anxiety symptoms is 51.3%, of depressive symptoms 41.2%, of PTSD symptoms 33.6%. Loneliness, hope, coping strategies, history of mental disorders were shared risk or protective factors across several psychotic symptoms. Perceived impact by COVID-19 is the specific risk factor associated with state anxiety symptoms. Conclusions The prevalence of symptoms of depression, anxiety and PTSS/PTSD is high among infected inpatients during the second wave of pandemic in Beijing. Clinical doctors must realize that infected inpatients during the second wave of pandemic are likely to suffer from depressive disorder, anxiety disorders and PTSS/PTSD, as well as some neuropsychiatric syndromes. Specific mental health care is urgently needed to help inpatients cope with the virus during the second wave of pandemic.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323519

ABSTRACT

Severe infectious diseases such as the novel coronavirus (COVID-19) pose a huge threat to public health. Stringent control measures, such as school closures and stay-at-home orders, while having significant effects, also bring huge economic losses. A crucial question for policymakers around the world is how to make the trade-off and implement the appropriate interventions. In this work, we propose a Multi-Objective Reinforcement Learning framework to facilitate the data-driven decision making and minimize the long-term overall cost. Specifically, at each decision point, a Bayesian epidemiological model is first learned as the environment model, and then we use the proposed model-based multi-objective planning algorithm to find a set of Pareto-optimal policies. This framework, combined with the prediction bands for each policy, provides a real-time decision support tool for policymakers. The application is demonstrated with the spread of COVID-19 in China.

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322743

ABSTRACT

Background: Towards the end of December 2019, the Wuhan health commission declared an outbreak of clusters of pneumonia in patients. Sequencing indicated that this disease (COVID-19) was caused by a novel coronavirus (SARS-CoV-2). The outbreak of COVID-19 is currently still underway. Methods We recruited 75 SARS-CoV-2 infected patients admitted to the Center of Infectious Disease division 2 of Beijing Ditan Hospital from Jan 20 to Mar 20, 2020. Epidemiological, demographic, clinical, radiological features, laboratory data were analyzed. Results Of the 75 patients, 42(56%) patients were male and 33(44%) patients were female. The mean age of all patients was 41.5 ± 19.4 years. Male patients were more likely to become severe. There were 9 family clusters accounted for 44 patients. Patients classified as being severe had a higher frequency of fever upon admission than patients classified as moderate cases. For moderate patients, the median duration of viral shedding was 25(9.5, 42) days (range 1–63 days) from the first positive nucleic acid test compared to 14(9, 21.25) days (range 2–62 days) for severe cases. The difference between the two groups was statistically significant (p = 0.041). Cox regression analyses indicated that disease status and CRP were the factors that affect the duration of viral shedding. Virus clearance was significantly faster in severe patients compared to moderate patients(p = 0.011), and patients with CRP range in 2–10 times higher than upper limit of normal value had longer duration of viral shedding(p = 0.012). CRP and CD4 + T lymphocyte was negative correlated, and the relationship between CRP and CD4 + T lymphocyte was statistically significant (P = 0.003), with a correlation coefficient of -0.564. During the second week following the onset of illness, severe cases had higher WBC, NEU and CRP, but lower LYM, MON and EOS as compared with moderate cases (all P < 0.05). Severe cases still had lower lymphocyte counts and higher CRP than moderate cases in the third week. Conclusions Viral clearance was significantly prolonged in moderate patients, and those CRP in 2–10 times higher than upper limit of normal value. Immune response may affect the duration of viral shedding. Severe cases had a persistence lower lymphocyte count and higher CRP than moderate cases.

14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315201

ABSTRACT

The mutations make uncertain to SARS-CoV-2 disease control and vaccine development. At population-level, single nucleotide polymorphism (SNPs) have displayed mutations for illustrating epidemiology, transmission, and pathogenesis of COVID-19. These mutations are to be expected by the analysis of intra-host level, which presented as intra-host variations (iSNVs). Here, we performed spatio-temporal analysis on iSNVs in 402 clinical samples from 170 patients, and observed an increase of genetic diversity along the day post symptom onset within individual patient and among subpopulations divided by gender, age, illness severity and viral shedding time, suggested a positive selection at intra-host level. The comparison of iSNVs and SNPs displayed that most of nonsynonymous mutations were not fixed suggested a purifying selection. This two-step fitness selection enforced iSNVs containing more nonsynonymous mutations, that highlight the potential characters of SARS-CoV-2 for viral infections and global transmissions.

15.
Liver Int ; 42(6): 1287-1296, 2022 06.
Article in English | MEDLINE | ID: covidwho-1666331

ABSTRACT

BACKGROUND AND AIMS: The safety and antibody responses of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic hepatitis B (CHB) virus infection is still unclear, and exploration in safety and antibody responses of COVID-19 vaccination in CHB patients is significant in clinical practice. METHODS: 362 adult CHB patients and 87 healthy controls at an interval of at least 21 days after a full-course vaccination (21-105 days) were enrolled. Adverse events (AEs) were collected by questionnaire. The antibody profiles at 1, 2 and 3 months were elucidated by determination of anti-spike IgG, anti-receptor-binding domain (RBD) IgG, and RBD-angiotensin-converting enzyme 2 blocking antibody. SARS-CoV-2 specific B cells were also analysed. RESULTS: All AEs were mild and self-limiting, and the incidence was similar between CHB patients and controls. Seropositivity rates of three antibodies were similar between CHB patients and healthy controls at 1, 2 and 3 months, but CHB patients had lower titers of three antibodies at 1 month. Compared to healthy controls, HBeAg-positive CHB patients had higher titers of three antibodies at 3 months (all P < .05) and a slower decline in antibody titers. Frequency of RBD-specific B cells was positively correlated with titers of anti-RBD IgG (OR = 1.067, P = .004), while liver cirrhosis, antiviral treatment, levels of HBV DNA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total bilirubin (TB) were not correlated with titers of anti-RBD IgG. CONCLUSIONS: Inactivated COVID-19 vaccines were well tolerated, and induced effective antibody response against SARS-CoV-2 in CHB patients.


Subject(s)
COVID-19 , Hepatitis B, Chronic , Adult , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Immunoglobulin G , SARS-CoV-2
16.
Growth and Change ; n/a(n/a), 2021.
Article in English | Wiley | ID: covidwho-1583564

ABSTRACT

As a public health emergency, the COVID-19 pandemic has attracted widespread attention from scholars worldwide. Combining social network models, GIS analysis and spatial econometric models, we explored the characteristics of the Wuhan population outflow network and factors affecting the number of COVID-19 cases. The results show that the Wuhan population outflow network has strong temporal and spatial heterogeneity. Cities in Hubei Province, central cities such as Beijing and Shanghai, and cities rich in tourism resources were the main destinations of Wuhan?s population inflow. The distribution of COVID-19 cases not only showed a strong spatial autocorrelation but also a hierarchical diffusion effect. The benchmark regression results showed that the population outflow from Wuhan determines the number of COVID-19 cases in other cities. Temperature was negatively correlated with the number of COVID-19 cases, while the PM2.5 concentration failed the significance test. Thus, the lower is the temperature, the greater are the survival and spread of the virus facilitated. Furthermore, cities with a higher population density and more employees in the middle reaches of the Yangtze River are more vulnerable to COVID-19. Finally, by replacing the weight matrix and setting instrumental variables, we proved the robustness of the above main conclusions.

17.
Cell Rep ; 38(2): 110205, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1588142

ABSTRACT

Spontaneous mutations introduce uncertainty into coronavirus disease 2019 (COVID-19) control procedures and vaccine development. Here, we perform a spatiotemporal analysis on intra-host single-nucleotide variants (iSNVs) in 402 clinical samples from 170 affected individuals, which reveals an increase in genetic diversity over time after symptom onset in individuals. Nonsynonymous mutations are overrepresented in the pool of iSNVs but underrepresented at the single-nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated in the host (positive selection), and these substitutions tend to be unfixed as SNPs in the population (negative selection). Dynamic iSNV changes in subpopulations with different gender, age, illness severity, and viral shedding time displayed a varied fitness selection process among populations. Our study highlights that iSNVs provide a mutational pool shaping the rapid global evolution of the virus.


Subject(s)
COVID-19/virology , Host-Pathogen Interactions/genetics , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Genome, Viral/genetics , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation/genetics , Phylogeny , Polymorphism, Single Nucleotide/genetics , Spike Glycoprotein, Coronavirus/genetics , Young Adult
19.
Clin Infect Dis ; 73(9): e2814-e2817, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501023

ABSTRACT

Intrahost analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences identified 2 viral haplotypes comprised of 3 genetically linked mutations from the respiratory and intestinal tracts of a patient with coronavirus disease 2019. Spatiotemporal data suggest that this patient initially had dual infection of 2 SARS-CoV-2 variants, which subsequently redistributed into the 2 systems.


Subject(s)
COVID-19 , SARS-CoV-2 , Genomics , Humans , Respiratory System
20.
Front Immunol ; 12: 735125, 2021.
Article in English | MEDLINE | ID: covidwho-1441109

ABSTRACT

Background: The global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR+CD38+ CD8+ T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38+HLA-DR+ CD8+ T population was reported to play contradictory roles in SARS-CoV-2 infection. Methods: A total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3-7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally. Results: We revealed that the HLA-DR+CD38+ CD8+ T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR+CD38dim and HLA-DR+CD38hi. We observed a persistent accumulation of HLA-DR+CD38hi CD8+ T cells in severe COVID-19 patients. These HLA-DR+CD38hi CD8+ T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR+CD38dim CD8+ T cells. Moreover, the clinical and laboratory data supported that only HLA-DR+CD38hi CD8+ T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients. Conclusions: Our findings indicated that HLA-DR+CD38hi CD8+ T cells were correlated with disease severity of COVID-19 rather than HLA-DR+CD38dim population.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immune System Diseases/immunology , SARS-CoV-2 , Adult , Aged , CD8 Antigens/immunology , Cytokines/immunology , Female , HLA-DR Antigens/immunology , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Young Adult
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