Pub Date : 2024-07-01Epub Date: 2024-06-12DOI: 10.1097/ID9.0000000000000128
{"title":"Guidelines for the Prevention, Diagnosis, Care and Treatment for People with Chronic Hepatitis B Infection (Text Extract): Executive Summary.","authors":"","doi":"10.1097/ID9.0000000000000128","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000128","url":null,"abstract":"","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":"4 3","pages":"103-105"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/ID9.0000000000000101
Yuming Guo, Zhe Xu, Wen-Xin Wang, C. Zhen, Jinhua Hu, Jinsong Mu, Chengcheng Ji, Xin Yuan, R. Xu, Lei Huang, Lei Shi, F. Meng, Jun‐liang Fu, Shuangnan Zhou, Siyu Wang, Fengyi Li, B. Tu, Dawei Zhang, Hui‐huang Huang, Yufeng Mao, Wenxin Xu, Chao Zhang, X. Mu, Jun Zhao, B. Jin, Haibin Su, Yinying Lu, Yongqian Cheng, Dong Ji, Shaoli You, Jing-hui Dong, Changchun Liu, Mengmeng Zhang, Yuan-yuan Li, T. Jiang, Yonggang Li, Furang Wang
Abstract Background The outbreak and prevalence of the Omicron variant have threatened human health since March 2022 in mainland China. In this study, we aimed to investigate the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) in the Beijing region. Methods In this retrospective study, we enrolled inpatients admitted for COVID-19 in the Fifth Medical Center of Chinese PLA General Hospital in Beijing between November 10, 2022, and January 30, 2023. Demographic and clinical features and treatment outcomes were comprehensively analyzed. We used logistic regression and linear regression analyses to explore the risk factors associated with disease severity and time of nucleic acid conversion, respectively. Results A total of 1010 hospitalized patients with COVID-19 were enrolled. The median age was 43.0 years (interquartile range, 28.0–63.0), and patients aged <60 years and ≥60 years comprised 71.2% and 28.8% of total included patients, respectively. The clinical classification of mild (74.6%, 753/1010), moderate (21.0%, 212/1010), severe (2.7%, 27/1010), and unidentified (1.8%, 18/1010) was separately recorded; 1005 patients were discharged, and 5 patients died in the hospital. The outbreak of the emerging epidemic witnessed an evident increase in the proportion of moderate (42.9% vs. 16.4%) and severe (10.3% vs. 1.1%) cases after December 7, 2022. Patients with a moderate/severe classification had higher levels of procalcitonin, IL-6, serum ferritin, C-reactive protein, lactic dehydrogenase, serum urea nitrogen, and d-dimer and lower counts of CD4+ T, CD8+ T, and B cells (all P < 0.001). Multivariable regression analysis revealed that increased odds of disease severity were associated with the following factors: age ≥60 years, IL-6 > 7 pg/mL, lactic dehydrogenase level >245 U/L, cough, and fever at admission. Age ≥80 years and chronic lung disease were independent risk factors in the nonmild group in elderly patients. In addition, the duration for nucleic acid to turn negative was approximately 5.0 d (interquartile range, 3.0–7.0). Prolonged time of nucleic acid conversion was associated with age ≥60 years, serum urea nitrogen level >8.2 mmol/L, neutrophil count >7 ×109/L, and the presence of a chronic lung disease or carcinoma. Finally, unvaccinated patients accounted for 37.3% of enrolled patients; children and the elder people accounted for approximately half of that. The univariable analysis found that booster doses reduced disease severity and shortened the time of nucleic acid conversion in elderly patients. Conclusions The outbreak of Omicron rapidly increased the number of patients with COVID-19 in Beijing. In elderly patients, booster doses may reduce disease severity and shorten the time of nucleic acid conversion. Healthcare systems should be optimized before an emerging epidemic outbreak.
{"title":"Clinical Epidemiology, Illness Profiles, and the Implication of COVID-19 Before and After the Nationwide Omicron Outbreak During the Winter of 2022","authors":"Yuming Guo, Zhe Xu, Wen-Xin Wang, C. Zhen, Jinhua Hu, Jinsong Mu, Chengcheng Ji, Xin Yuan, R. Xu, Lei Huang, Lei Shi, F. Meng, Jun‐liang Fu, Shuangnan Zhou, Siyu Wang, Fengyi Li, B. Tu, Dawei Zhang, Hui‐huang Huang, Yufeng Mao, Wenxin Xu, Chao Zhang, X. Mu, Jun Zhao, B. Jin, Haibin Su, Yinying Lu, Yongqian Cheng, Dong Ji, Shaoli You, Jing-hui Dong, Changchun Liu, Mengmeng Zhang, Yuan-yuan Li, T. Jiang, Yonggang Li, Furang Wang","doi":"10.1097/ID9.0000000000000101","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000101","url":null,"abstract":"Abstract Background The outbreak and prevalence of the Omicron variant have threatened human health since March 2022 in mainland China. In this study, we aimed to investigate the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) in the Beijing region. Methods In this retrospective study, we enrolled inpatients admitted for COVID-19 in the Fifth Medical Center of Chinese PLA General Hospital in Beijing between November 10, 2022, and January 30, 2023. Demographic and clinical features and treatment outcomes were comprehensively analyzed. We used logistic regression and linear regression analyses to explore the risk factors associated with disease severity and time of nucleic acid conversion, respectively. Results A total of 1010 hospitalized patients with COVID-19 were enrolled. The median age was 43.0 years (interquartile range, 28.0–63.0), and patients aged <60 years and ≥60 years comprised 71.2% and 28.8% of total included patients, respectively. The clinical classification of mild (74.6%, 753/1010), moderate (21.0%, 212/1010), severe (2.7%, 27/1010), and unidentified (1.8%, 18/1010) was separately recorded; 1005 patients were discharged, and 5 patients died in the hospital. The outbreak of the emerging epidemic witnessed an evident increase in the proportion of moderate (42.9% vs. 16.4%) and severe (10.3% vs. 1.1%) cases after December 7, 2022. Patients with a moderate/severe classification had higher levels of procalcitonin, IL-6, serum ferritin, C-reactive protein, lactic dehydrogenase, serum urea nitrogen, and d-dimer and lower counts of CD4+ T, CD8+ T, and B cells (all P < 0.001). Multivariable regression analysis revealed that increased odds of disease severity were associated with the following factors: age ≥60 years, IL-6 > 7 pg/mL, lactic dehydrogenase level >245 U/L, cough, and fever at admission. Age ≥80 years and chronic lung disease were independent risk factors in the nonmild group in elderly patients. In addition, the duration for nucleic acid to turn negative was approximately 5.0 d (interquartile range, 3.0–7.0). Prolonged time of nucleic acid conversion was associated with age ≥60 years, serum urea nitrogen level >8.2 mmol/L, neutrophil count >7 ×109/L, and the presence of a chronic lung disease or carcinoma. Finally, unvaccinated patients accounted for 37.3% of enrolled patients; children and the elder people accounted for approximately half of that. The univariable analysis found that booster doses reduced disease severity and shortened the time of nucleic acid conversion in elderly patients. Conclusions The outbreak of Omicron rapidly increased the number of patients with COVID-19 in Beijing. In elderly patients, booster doses may reduce disease severity and shorten the time of nucleic acid conversion. Healthcare systems should be optimized before an emerging epidemic outbreak.","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":"212 1","pages":"176 - 185"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139326668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract This study aimed to investigate the status of and changes in the vaccination willingness of patients with breast cancer to increase the coronavirus disease 2019 (COVID-19) vaccination rate among these patients. The first survey included patients from the Fifth Medical Center of the PLA General Hospital who participated in the Society of Clinical Oncology Breast Cancer Committee NCP-02 study conducted from September 16 to December 31, 2021. The second survey was conducted from December 9 to December 26, 2022, for those who had not received vaccines previously. In total, 266 patients completed two questionnaires. A total of 143 patients (53.8%) changed their willingness to receive the vaccination. Among them, 45, who were initially unwilling to be vaccinated, changed their stance to become hesitant and 15 changed to become willing. Among those with hesitant attitudes toward vaccines, 45 changed their stance to become willing, and 28 changed to become unwilling; 10 patients with willing attitudes toward vaccines changed to become hesitant. Those who received surgery (odds ratio (OR), 4.24; 95% confidence interval (CI), 1.45–12.42; P = 0.01) and who lived with older adults or children (OR, 2.03; 95% CI, 1.13–3.62; P = 0.02) were more likely to change their attitudes toward COVID-19 vaccines. This finding suggested that patients with breast cancer were cautious about receiving the COVID-19 vaccine. Multiple methods should be used to promote vaccination and reduce vaccine hesitancy.
{"title":"Survey on Changes in the Willingness to Receive the COVID-19 Vaccine Among Patients with Breast Cancer in the Postpandemic Era","authors":"Lixiao Bai, Jianbin Li, Ailing Yang, Cuicui Ding, Jiayi Li, Yan Wang, Liangying Li, Shaohua Zhang, Zefei Jiang","doi":"10.1097/id9.0000000000000097","DOIUrl":"https://doi.org/10.1097/id9.0000000000000097","url":null,"abstract":"Abstract This study aimed to investigate the status of and changes in the vaccination willingness of patients with breast cancer to increase the coronavirus disease 2019 (COVID-19) vaccination rate among these patients. The first survey included patients from the Fifth Medical Center of the PLA General Hospital who participated in the Society of Clinical Oncology Breast Cancer Committee NCP-02 study conducted from September 16 to December 31, 2021. The second survey was conducted from December 9 to December 26, 2022, for those who had not received vaccines previously. In total, 266 patients completed two questionnaires. A total of 143 patients (53.8%) changed their willingness to receive the vaccination. Among them, 45, who were initially unwilling to be vaccinated, changed their stance to become hesitant and 15 changed to become willing. Among those with hesitant attitudes toward vaccines, 45 changed their stance to become willing, and 28 changed to become unwilling; 10 patients with willing attitudes toward vaccines changed to become hesitant. Those who received surgery (odds ratio (OR), 4.24; 95% confidence interval (CI), 1.45–12.42; P = 0.01) and who lived with older adults or children (OR, 2.03; 95% CI, 1.13–3.62; P = 0.02) were more likely to change their attitudes toward COVID-19 vaccines. This finding suggested that patients with breast cancer were cautious about receiving the COVID-19 vaccine. Multiple methods should be used to promote vaccination and reduce vaccine hesitancy.","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135878624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-15DOI: 10.1097/ID9.0000000000000100
Valentina V. Tatarnikova, N. O. Kiseleva, V. .. Dubrovina, V. A. Vishnyakov, D. D. Bryukhova, A. B. Pyatidesyatnikova, K. Korytov, M. B. Sharakshanov, S. Balakhonov
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ systemic damage that can lead to long-term consequences. Little is known about the possible long-term effects of COVID-19 on circulating leukocyte kinetics and functional T-cell activity after recovery. To investigate immune system changes, we designed a cohort study. Methods Volunteer screening and sample collection were performed at the Irkutsk Research Anti-Plague Institute of Rospotrebnadzor. Sixty-four volunteers who have had COVID-19 (recovered volunteers (RVs)) between May 2020 and May 2021, 33 volunteers who had been in contact with COVID-19 patients (contact volunteers (CVs)) within the family setting but had not become ill, and 47 healthy volunteers (HVs) participated in the study. We performed immunophenotyping of peripheral blood cells using flow cytometry. Serum was tested for SARS-CoV-2 anti-nucleocapsid immunoglobulin G antibodies by enzyme-linked immunosorbent assay (Ab(+), people with specific anti-N antibodies to SARS-CoV-2; Ab(−), people without specific antibodies). Results There were no serious disturbances in the internal environment of the body in RVs and CVs. In the evaluation of the general state of the immune system, the most informative indicator was the index of the ratio of neutrophils to blood monocytes – decreased on the 1st terms of observation (1 and 3 months post-symptom onset (PSO)/post-contact onset (PCO)), on average, 1.3 times compared with HVs (8.6% (7.5%–10.5%), P < 0.05), which recovered by the 6th month of observation. Redistribution of the cells responsible for the development of the adaptive immune response was noted only in RVs – increased B-lymphocyte content (HVs, 9.1% (6.4%–10.2%)) and immunoregulatory index ratio (HVs, 1.6% (1.2%–2.1%)) due to redistribution of T-helper and cytotoxic T cells throughout the follow-up period by an average of 1.2-fold compared with HVs (P < 0.05). However, CVs with specific antibodies to SARS-CoV-2 N-protein also had an increased proportion of CD3−CD19+ cells after 1 month PCO (Ab(+), 11.4% (10.2%–15.1%); Ab(−), 8.6% (5.7%–9.7%); P = 0.006). A significant difference between RVs and CVs is that the RVs showed significant activation of circulating T cells, which persisted up to the 6th month of the study, whereas in CVs, it persisted for 3 months PCO. The highest proportion of HLA-DR+ T-lymphocytes was recorded after 1 month PSO/PCO in Ab(+) RVs and CVs: Ab(+) volunteers, 8.1% (6.0%–11.2%) and 4.4% (2.7%–6.4%), respectively; Ab(−) volunteers, 4.2% (2.6%–5.4%) and 5.1% (3.7%–5.6%); and HVs, 3.5% (2.5%–4.7%) (P < 0.01). In CVs, natural killer cells also played a major role in preventing manifest infection (CVs, 10.8% ± 4.3%; HVs, 15.9% ± 7.6%; P < 0.05). Conclusion In this study, we demonstrated the dynamics of returning to the initial state of health in RVs and CVs. In CVs, we observed changes in the studied immunological parameters similar to those of RVs, but which are
{"title":"Immune Profile of COVID-19 Survivors and Contacts During 9 Months: A Cohort Study","authors":"Valentina V. Tatarnikova, N. O. Kiseleva, V. .. Dubrovina, V. A. Vishnyakov, D. D. Bryukhova, A. B. Pyatidesyatnikova, K. Korytov, M. B. Sharakshanov, S. Balakhonov","doi":"10.1097/ID9.0000000000000100","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000100","url":null,"abstract":"Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ systemic damage that can lead to long-term consequences. Little is known about the possible long-term effects of COVID-19 on circulating leukocyte kinetics and functional T-cell activity after recovery. To investigate immune system changes, we designed a cohort study. Methods Volunteer screening and sample collection were performed at the Irkutsk Research Anti-Plague Institute of Rospotrebnadzor. Sixty-four volunteers who have had COVID-19 (recovered volunteers (RVs)) between May 2020 and May 2021, 33 volunteers who had been in contact with COVID-19 patients (contact volunteers (CVs)) within the family setting but had not become ill, and 47 healthy volunteers (HVs) participated in the study. We performed immunophenotyping of peripheral blood cells using flow cytometry. Serum was tested for SARS-CoV-2 anti-nucleocapsid immunoglobulin G antibodies by enzyme-linked immunosorbent assay (Ab(+), people with specific anti-N antibodies to SARS-CoV-2; Ab(−), people without specific antibodies). Results There were no serious disturbances in the internal environment of the body in RVs and CVs. In the evaluation of the general state of the immune system, the most informative indicator was the index of the ratio of neutrophils to blood monocytes – decreased on the 1st terms of observation (1 and 3 months post-symptom onset (PSO)/post-contact onset (PCO)), on average, 1.3 times compared with HVs (8.6% (7.5%–10.5%), P < 0.05), which recovered by the 6th month of observation. Redistribution of the cells responsible for the development of the adaptive immune response was noted only in RVs – increased B-lymphocyte content (HVs, 9.1% (6.4%–10.2%)) and immunoregulatory index ratio (HVs, 1.6% (1.2%–2.1%)) due to redistribution of T-helper and cytotoxic T cells throughout the follow-up period by an average of 1.2-fold compared with HVs (P < 0.05). However, CVs with specific antibodies to SARS-CoV-2 N-protein also had an increased proportion of CD3−CD19+ cells after 1 month PCO (Ab(+), 11.4% (10.2%–15.1%); Ab(−), 8.6% (5.7%–9.7%); P = 0.006). A significant difference between RVs and CVs is that the RVs showed significant activation of circulating T cells, which persisted up to the 6th month of the study, whereas in CVs, it persisted for 3 months PCO. The highest proportion of HLA-DR+ T-lymphocytes was recorded after 1 month PSO/PCO in Ab(+) RVs and CVs: Ab(+) volunteers, 8.1% (6.0%–11.2%) and 4.4% (2.7%–6.4%), respectively; Ab(−) volunteers, 4.2% (2.6%–5.4%) and 5.1% (3.7%–5.6%); and HVs, 3.5% (2.5%–4.7%) (P < 0.01). In CVs, natural killer cells also played a major role in preventing manifest infection (CVs, 10.8% ± 4.3%; HVs, 15.9% ± 7.6%; P < 0.05). Conclusion In this study, we demonstrated the dynamics of returning to the initial state of health in RVs and CVs. In CVs, we observed changes in the studied immunological parameters similar to those of RVs, but which are","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":"91 1","pages":"163 - 175"},"PeriodicalIF":0.0,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139350494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2022-10-21DOI: 10.1097/ID9.0000000000000076
Xiaoyan Li, Xin Yuan, Zhe Xu, Lei Shi, Lei Huang, Xuechun Lu, Junliang Fu
<p><strong>Background: </strong>Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19.</p><p><strong>Methods: </strong>This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors.</p><p><strong>Results: </strong>Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% <i>vs.</i> 1.65%, <i>P</i> < 0.001), which was maintained after propensity score matching (13.98% <i>vs.</i> 5.38%, <i>P</i> = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242; 95% confidence interval [CI], 0.802 to 34.246; <i>P</i> = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327; 95% CI, 1.702 to 6.501; <i>P</i> < 0.001), lower lymphocyte count (OR, 0.076; 95% CI, 0.012 to 0.461; <i>P</i> = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008; 95% CI, 1.003 to 1.013; <i>P</i> = 0.002), and anticoagulation therapy (OR, 11.187; 95% CI, 2.459 to 50.900; <i>P</i> = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (β Value 0.081; 95% CI, -1.012 to 3.657; <i>P</i> = 0.265) or discharge (β Value 0.114; 95% CI, -0.723 to 6.408; <i>P</i> = 0.117). d-dimer (β Value, 0.144; 95% CI, 0.012 to 0.817; <i>P</i> = 0.044), LDH (β Value 0.260; 95% CI, 0.010 to 0.034; <i>P</i> < 0.001), and antiviral therapy (β Value 0.220; 95% CI, 1.373 to 6.263; <i>P</i> = 0.002) were associated with a longer length from admission to viral clearance. The lym
{"title":"Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis.","authors":"Xiaoyan Li, Xin Yuan, Zhe Xu, Lei Shi, Lei Huang, Xuechun Lu, Junliang Fu","doi":"10.1097/ID9.0000000000000076","DOIUrl":"10.1097/ID9.0000000000000076","url":null,"abstract":"<p><strong>Background: </strong>Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19.</p><p><strong>Methods: </strong>This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors.</p><p><strong>Results: </strong>Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% <i>vs.</i> 1.65%, <i>P</i> < 0.001), which was maintained after propensity score matching (13.98% <i>vs.</i> 5.38%, <i>P</i> = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242; 95% confidence interval [CI], 0.802 to 34.246; <i>P</i> = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327; 95% CI, 1.702 to 6.501; <i>P</i> < 0.001), lower lymphocyte count (OR, 0.076; 95% CI, 0.012 to 0.461; <i>P</i> = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008; 95% CI, 1.003 to 1.013; <i>P</i> = 0.002), and anticoagulation therapy (OR, 11.187; 95% CI, 2.459 to 50.900; <i>P</i> = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (β Value 0.081; 95% CI, -1.012 to 3.657; <i>P</i> = 0.265) or discharge (β Value 0.114; 95% CI, -0.723 to 6.408; <i>P</i> = 0.117). d-dimer (β Value, 0.144; 95% CI, 0.012 to 0.817; <i>P</i> = 0.044), LDH (β Value 0.260; 95% CI, 0.010 to 0.034; <i>P</i> < 0.001), and antiviral therapy (β Value 0.220; 95% CI, 1.373 to 6.263; <i>P</i> = 0.002) were associated with a longer length from admission to viral clearance. The lym","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":"3 1","pages":"20-28"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/72/84/idi-3-20.PMC9912987.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10737780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Background The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has greatly threatened public health. Recent studies have revealed that the spike receptor-binding domain (RBD) of SARS-CoV-2 is a potent target for vaccine development. However, adjuvants are usually required to strengthen the immunogenicity of recombinant antigens. Different types of adjuvants can elicit different immune responses. Methods We developed an RBD recombinant protein vaccine with a polyriboinosinic acid–polyribocytidylic acid [poly(I:C)] adjuvant to evoke a strong immune response. The delivery of poly(I:C) was optimized in two steps. First, poly(I:C) was complexed with a cationic polymer, poly-l-lysine (PLL), to form poly(I:C)–PLL, a polyplex core. Thereafter, it was loaded into five different lipid shells (group II, III-1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC], III-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine [DOPE], IV-DOPE, and IV-DSPC). We performed an enzyme-linked immunosorbent assay and enzyme-linked immunosorbent spot assay to compare the ability of the five lipopolyplex adjuvants to enhance the immunogenicity of the SARS-CoV-2 RBD protein, including humoral and cellular immune responses. Finally, the adjuvant with the highest immunogenicity was selected to verify the protective immunity of the vaccine through animal challenge experiments. Results Recombinant RBD protein has low immunogenicity. The different adjuvants we developed enhanced the immunogenicity of the RBD protein in different ways. Among the lipopolyplexes, those containing DOPE (III-DOPE and IV-DOPE) elicited RBD-specific immunoglobulin G antibody responses, and adjuvants with four components elicited better RBD-specific immunoglobulin G antibody responses than those containing three components (P < 0.05). The IC50 and IC90 titers indicated that the IV-DOPE lipopolyplex had the greatest neutralization ability, with IC50 titers of 1/117,490. Furthermore, in the challenge study, IV-DOPE lipopolyplex protected mice from SARS-CoV-2 infection. On the fourth day after infection, the average animal body weights were reduced by 18.56% (24.164 ± 0.665 g vs. 19.678 ± 0.455 g) and 0.06% (24.249 ± 0.683 g vs. 24.235 ± 0.681 g) in the MOCK and vaccine groups, respectively. In addition, the relative expression of viral RNA in the vaccinated group was significantly lower than that in the MOCK group (P < 0.05). Interstitial inflammatory cell infiltration was observed in the MOCK group, whereas no obvious damage was observed in the vaccinated group. Conclusions The IV-DOPE–adjuvanted SARS-CoV-2 recombinant RBD protein vaccine efficiently protected mice from SARS-CoV-2 in the animal challenge study. Therefore, IV-DOPE is considered an exceptional adjuvant for SARS-CoV-2 recombinant RBD protein-based vaccines and has the potential to be further developed into a SARS-CoV-2 recombinant RBD protein-based vaccine.
摘要背景严重急性呼吸系统综合征冠状病毒2型的爆发严重威胁着公众健康。最近的研究表明,严重急性呼吸系统综合征冠状病毒2型的刺突受体结合域(RBD)是疫苗开发的有力靶点。然而,通常需要佐剂来增强重组抗原的免疫原性。不同类型的佐剂可以引发不同的免疫反应。方法我们开发了一种含有聚核糖肌苷酸-聚核糖胞苷酸[聚(I:C)]佐剂的RBD重组蛋白疫苗,以引起强烈的免疫反应。聚(I:C)的递送分两步进行优化。首先,将poly(I:C)与阳离子聚合物聚赖氨酸(PLL)络合,形成poly(1:C)–PLL,一种多聚物核。此后,将其装载到五种不同的脂质壳中(第II组,III-1,2-二硬脂酰基-sn-甘油-3-磷酸胆碱[DPC]、III-1,2-二醇酰基-sn-葡萄糖-3-磷酸乙醇胺[DOPE]、IV-DOPE和IV-DSPC)。我们进行了酶联免疫吸附试验和酶联免疫斑点试验,以比较五种脂多糖佐剂增强严重急性呼吸系统综合征冠状病毒2型RBD蛋白免疫原性的能力,包括体液和细胞免疫反应。最后,选择免疫原性最高的佐剂,通过动物攻击实验验证疫苗的保护性免疫。结果重组RBD蛋白具有较低的免疫原性。我们开发的不同佐剂以不同的方式增强RBD蛋白的免疫原性。在脂溶性复合物中,含有DOPE的(III-DOPE和IV-DOPE)能引发RBD特异性免疫球蛋白G抗体反应,而含有四种成分的佐剂比含有三种成分的辅料能引发更好的RBD特异性免疫球蛋白G抗体反应(P<0.05),IC50滴度为1/117490。此外,在挑战性研究中,IV-DOPE脂多糖保护小鼠免受严重急性呼吸系统综合征冠状病毒2型感染。感染后第4天,MOCK组和疫苗组的平均动物体重分别减少了18.56%(24.164±0.665 g vs.19.678±0.455 g)和0.06%(24.249±0.683 g vs.24.235±0.681 g)。此外,接种组病毒RNA的相对表达显著低于对照组(P<0.05)。对照组间质炎症细胞浸润,而接种组未观察到明显损伤。结论在动物攻击研究中,IV-DOPE佐剂的严重急性呼吸系统综合征冠状病毒2型重组RBD蛋白疫苗有效地保护小鼠免受严重急性呼吸综合征冠状病毒的感染。因此,IV-DOPE被认为是基于严重急性呼吸系统综合征冠状病毒2型重组RBD蛋白的疫苗的一种特殊佐剂,并有可能进一步发展成为基于严重急性呼吸道综合征冠状病毒2中重组RBD蛋白质的疫苗。
{"title":"Lipid-Based Poly(I:C) Adjuvants Strongly Enhance the Immunogenicity of SARS-CoV-2 Receptor-Binding Domain Vaccine","authors":"Yixin Wu, Liuxian Meng, Huicong Zhang, Shun-guang Hu, Fusheng Li, Yingjie Yu","doi":"10.1097/ID9.0000000000000074","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000074","url":null,"abstract":"Abstract Background The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has greatly threatened public health. Recent studies have revealed that the spike receptor-binding domain (RBD) of SARS-CoV-2 is a potent target for vaccine development. However, adjuvants are usually required to strengthen the immunogenicity of recombinant antigens. Different types of adjuvants can elicit different immune responses. Methods We developed an RBD recombinant protein vaccine with a polyriboinosinic acid–polyribocytidylic acid [poly(I:C)] adjuvant to evoke a strong immune response. The delivery of poly(I:C) was optimized in two steps. First, poly(I:C) was complexed with a cationic polymer, poly-l-lysine (PLL), to form poly(I:C)–PLL, a polyplex core. Thereafter, it was loaded into five different lipid shells (group II, III-1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC], III-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine [DOPE], IV-DOPE, and IV-DSPC). We performed an enzyme-linked immunosorbent assay and enzyme-linked immunosorbent spot assay to compare the ability of the five lipopolyplex adjuvants to enhance the immunogenicity of the SARS-CoV-2 RBD protein, including humoral and cellular immune responses. Finally, the adjuvant with the highest immunogenicity was selected to verify the protective immunity of the vaccine through animal challenge experiments. Results Recombinant RBD protein has low immunogenicity. The different adjuvants we developed enhanced the immunogenicity of the RBD protein in different ways. Among the lipopolyplexes, those containing DOPE (III-DOPE and IV-DOPE) elicited RBD-specific immunoglobulin G antibody responses, and adjuvants with four components elicited better RBD-specific immunoglobulin G antibody responses than those containing three components (P < 0.05). The IC50 and IC90 titers indicated that the IV-DOPE lipopolyplex had the greatest neutralization ability, with IC50 titers of 1/117,490. Furthermore, in the challenge study, IV-DOPE lipopolyplex protected mice from SARS-CoV-2 infection. On the fourth day after infection, the average animal body weights were reduced by 18.56% (24.164 ± 0.665 g vs. 19.678 ± 0.455 g) and 0.06% (24.249 ± 0.683 g vs. 24.235 ± 0.681 g) in the MOCK and vaccine groups, respectively. In addition, the relative expression of viral RNA in the vaccinated group was significantly lower than that in the MOCK group (P < 0.05). Interstitial inflammatory cell infiltration was observed in the MOCK group, whereas no obvious damage was observed in the vaccinated group. Conclusions The IV-DOPE–adjuvanted SARS-CoV-2 recombinant RBD protein vaccine efficiently protected mice from SARS-CoV-2 in the animal challenge study. Therefore, IV-DOPE is considered an exceptional adjuvant for SARS-CoV-2 recombinant RBD protein-based vaccines and has the potential to be further developed into a SARS-CoV-2 recombinant RBD protein-based vaccine.","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":"3 1","pages":"3 - 12"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42741329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01DOI: 10.1097/ID9.0000000000000070
Qiankun Wang, Liang Shan
Innate immune responses are the host's first line of defense against human immunodeficiency virus type 1 (HIV-1) infection, with pattern recognition receptors detecting viral specific pathogen-associated molecular patterns and initiating antiviral responses. In response to HIV-1 nucleic acids or proteins, some pattern recognition receptors have the ability to assemble a large multiprotein complex called the inflammasome, which triggers pro-inflammatory cytokine release and a form of lytic programmed cell death called pyroptosis. Here, we review our current understanding of the mechanism of the inflammasome in sensing HIV-1 infection. Furthermore, we discuss the contribution of inflammasome activation in HIV-1 pathogenesis as well as potential strategies of targeting inflammasome activation for the treatment of HIV-1 infection.
{"title":"Inflammasomes in Human Immunodeficiency Virus Type 1 Infection.","authors":"Qiankun Wang, Liang Shan","doi":"10.1097/ID9.0000000000000070","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000070","url":null,"abstract":"<p><p>Innate immune responses are the host's first line of defense against human immunodeficiency virus type 1 (HIV-1) infection, with pattern recognition receptors detecting viral specific pathogen-associated molecular patterns and initiating antiviral responses. In response to HIV-1 nucleic acids or proteins, some pattern recognition receptors have the ability to assemble a large multiprotein complex called the inflammasome, which triggers pro-inflammatory cytokine release and a form of lytic programmed cell death called pyroptosis. Here, we review our current understanding of the mechanism of the inflammasome in sensing HIV-1 infection. Furthermore, we discuss the contribution of inflammasome activation in HIV-1 pathogenesis as well as potential strategies of targeting inflammasome activation for the treatment of HIV-1 infection.</p>","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":"2 4","pages":"248-252"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/40/68/idi-2-248.PMC9923888.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10748469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Severe acute respiratory syndrome coronavirus-2 infection is usually self-limited, with a short duration for viral shedding within several weeks. However, prolonged viral shedding has been observed in severe or immune-compromised coronavirus disease 2019 (COVID-19) cases. Here, we reported that three young adult cases of COVID-19 patients, who were either immunosuppressed nor severe, showed prolonged viral RNA shedding from the upper respiratory tract for 58, 81, and 137 days since initial diagnosis. To our knowledge, this is the longest duration of viral shedding reported to date in young adult patients. Further studies on factors relevant to prolonged viral positivity, as well as the correlation between viral positivity and transmission risk are needed for the optimal management of COVID-19 patients with prolonged nucleic acid positive.
{"title":"Prolonged Viral Shedding in Three Young Adult Cases of COVID-19.","authors":"Wen-Yi Dong, Ming-Ju Zhou, Lei Huang, Chao Zhang, Fu-Sheng Wang, Zhou-Hua Xie","doi":"10.1097/ID9.0000000000000041","DOIUrl":"10.1097/ID9.0000000000000041","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus-2 infection is usually self-limited, with a short duration for viral shedding within several weeks. However, prolonged viral shedding has been observed in severe or immune-compromised coronavirus disease 2019 (COVID-19) cases. Here, we reported that three young adult cases of COVID-19 patients, who were either immunosuppressed nor severe, showed prolonged viral RNA shedding from the upper respiratory tract for 58, 81, and 137 days since initial diagnosis. To our knowledge, this is the longest duration of viral shedding reported to date in young adult patients. Further studies on factors relevant to prolonged viral positivity, as well as the correlation between viral positivity and transmission risk are needed for the optimal management of COVID-19 patients with prolonged nucleic acid positive.</p>","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":"2 4","pages":"289-292"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/74/idi-2-289.PMC9612418.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9912576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01Epub Date: 2022-09-01DOI: 10.1097/ID9.0000000000000065
Junyan Jin, Xiuwen Wang, Raphael Carapito, Christiane Moog, Bin Su
{"title":"Advances in Research on COVID-19 Vaccination for People Living with HIV.","authors":"Junyan Jin, Xiuwen Wang, Raphael Carapito, Christiane Moog, Bin Su","doi":"10.1097/ID9.0000000000000065","DOIUrl":"10.1097/ID9.0000000000000065","url":null,"abstract":"","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":"2 4","pages":"213-218"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/20/de/idi-2-213.PMC9612416.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9912577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01DOI: 10.1097/ID9.0000000000000056
Micah Hartwell, Benjamin H Greiner, Savannah Nicks
As the SARS-CoV-2 virus shares relatively large protein sequences homologous to grass pollens, dust mites, and molds, our objective was to assess the potential overlap between the COVID-19 mRNA vaccines from Pfizer-BioNtech and Moderna and known allergens. We found 7 common allergens with potential for cross-reactivity with the Pfizer vaccine and 19 with the Moderna vaccine, including common grasses, molds, and dust mites. T-cell mediated antigen cross-reactivity between viruses and allergens is a relatively new area of study in clinical immunology; a discipline that may be particularly useful regarding the SARS-CoV-2 virus and the allergic response in humans. These results suggest that vaccination with the Pfizer-BioNtech and Moderna COVID-19 vaccines may contribute to T-cell cross-reactivity with allergens that impact allergic asthma and allergic rhinitis. Further research should assess the clinical implications of COVID-19 vaccination on the severity and symptomatology of the allergic disease, in addition to natural viral infection.
{"title":"Examination of Homologies between COVID-19 Vaccines and Common Allergens: The Potential for T Cell-mediated Responses for Allergic Rhinitis and Asthma.","authors":"Micah Hartwell, Benjamin H Greiner, Savannah Nicks","doi":"10.1097/ID9.0000000000000056","DOIUrl":"https://doi.org/10.1097/ID9.0000000000000056","url":null,"abstract":"<p><p>As the SARS-CoV-2 virus shares relatively large protein sequences homologous to grass pollens, dust mites, and molds, our objective was to assess the potential overlap between the COVID-19 mRNA vaccines from Pfizer-BioNtech and Moderna and known allergens. We found 7 common allergens with potential for cross-reactivity with the Pfizer vaccine and 19 with the Moderna vaccine, including common grasses, molds, and dust mites. T-cell mediated antigen cross-reactivity between viruses and allergens is a relatively new area of study in clinical immunology; a discipline that may be particularly useful regarding the SARS-CoV-2 virus and the allergic response in humans. These results suggest that vaccination with the Pfizer-BioNtech and Moderna COVID-19 vaccines may contribute to T-cell cross-reactivity with allergens that impact allergic asthma and allergic rhinitis. Further research should assess the clinical implications of COVID-19 vaccination on the severity and symptomatology of the allergic disease, in addition to natural viral infection.</p>","PeriodicalId":73371,"journal":{"name":"Infectious diseases & immunity","volume":"2 4","pages":"282-284"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/d5/idi-2-282.PMC9612419.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10294646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}