1.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
2.Comparison of five virus enrichment methods for drinking water
Mengdi TAN ; Zhiyong GAO ; Jiachen ZHAO ; Hanqiu YAN ; Weihong LI ; Daitao ZHANG ; Quanyi WANG ; Weixian SHI
Chinese Journal of Experimental and Clinical Virology 2025;39(1):102-108
Objective:To compare the enrichment effects of ultrafiltration, polyethylene glycol (PEG) precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution on viruses in drinking water.Methods:Using phage MS2 as the target virus, three different concentrations of drinking water samples were prepared, and the samples were enriched by ultrafiltration 1, ultrafiltration 2, PEG precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution method, respectively. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to quantify MS2 nucleic acid in pre and post concentrated samples and the recovery rates of MS2 in samples with high, medium and low concentrations were compared among the five methods.Results:Comparing the MS2 enrichment recovery rates of individual enrichment method in water samples of different concentrations, ultrafiltration method 1, PEG precipitation method, aluminum salt precipitation method, and membrane adsorption-elution method were not affected by the sample concentration, and the differences of the recovery rates for the three concentration water samples among the four methods were not statistically significant ( P>0.05). The MS2 enrichment recovery rates of the five enrichment methods were significantly different in all concentration samples ( P<0.05). The recovery rates of ultrafiltration method 1 were higher in all three concentration samples, followed by aluminum salt precipitation and anionic membrane adsorption-elution, PEG precipitation were higher in high concentration samples, but lower in low and medium concentration samples, and the recovery rates of ultrafiltration method 2 were the lowest in all three concentration samples. Comparing the Ct values of MS2 in the enriched samples by five methods, the Ct values of ultrafiltration method 1 were the smallest in the three concentration water samples. There was no statistically significant difference in MS2 Ct values among the five enrichment methods in the medium and high concentration water samples ( P>0.05). In low concentration simulated water samples, only the difference of MS2 Ct value between ultrafiltration method 1 and ultrafiltration method 2 was statistically significant ( Z=16.000, P=0.016). Conclusions:Considering the operation simplicity, operation time and virus recovery rate after enrichment, ultrafiltration was the most effective method for virus enrichment in drinking water.
3.Comparison of five virus enrichment methods for drinking water
Mengdi TAN ; Zhiyong GAO ; Jiachen ZHAO ; Hanqiu YAN ; Weihong LI ; Daitao ZHANG ; Quanyi WANG ; Weixian SHI
Chinese Journal of Experimental and Clinical Virology 2025;39(1):102-108
Objective:To compare the enrichment effects of ultrafiltration, polyethylene glycol (PEG) precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution on viruses in drinking water.Methods:Using phage MS2 as the target virus, three different concentrations of drinking water samples were prepared, and the samples were enriched by ultrafiltration 1, ultrafiltration 2, PEG precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution method, respectively. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to quantify MS2 nucleic acid in pre and post concentrated samples and the recovery rates of MS2 in samples with high, medium and low concentrations were compared among the five methods.Results:Comparing the MS2 enrichment recovery rates of individual enrichment method in water samples of different concentrations, ultrafiltration method 1, PEG precipitation method, aluminum salt precipitation method, and membrane adsorption-elution method were not affected by the sample concentration, and the differences of the recovery rates for the three concentration water samples among the four methods were not statistically significant ( P>0.05). The MS2 enrichment recovery rates of the five enrichment methods were significantly different in all concentration samples ( P<0.05). The recovery rates of ultrafiltration method 1 were higher in all three concentration samples, followed by aluminum salt precipitation and anionic membrane adsorption-elution, PEG precipitation were higher in high concentration samples, but lower in low and medium concentration samples, and the recovery rates of ultrafiltration method 2 were the lowest in all three concentration samples. Comparing the Ct values of MS2 in the enriched samples by five methods, the Ct values of ultrafiltration method 1 were the smallest in the three concentration water samples. There was no statistically significant difference in MS2 Ct values among the five enrichment methods in the medium and high concentration water samples ( P>0.05). In low concentration simulated water samples, only the difference of MS2 Ct value between ultrafiltration method 1 and ultrafiltration method 2 was statistically significant ( Z=16.000, P=0.016). Conclusions:Considering the operation simplicity, operation time and virus recovery rate after enrichment, ultrafiltration was the most effective method for virus enrichment in drinking water.
4.Clinical observation of the effect of nirmatrelvir/ritonavir on renal function in patients with coronavirus disease 2019 and renal insufficiency
Jin′e PENG ; Hui LIU ; Jianying XIA ; Shuo WANG ; Hanqiu ZHAN
Adverse Drug Reactions Journal 2024;26(5):275-279
Objective:To explore the effect of nirmatrelvir/ritonavir (Paxlovid) on renal function in patients with coronavirus disease 2019 (COVID-19) and renal insufficiency.Methods:Clinical data of renal insufficiency patients with COVID-19, who were hospitalized at Beijing Ditan Hospital, Capital Medical University from March 23, 2022 to April 30, 2023 and received Paxlovid treatment, were collected. A retrospective analysis was conducted on the incidence of Paxlovid-related acute kidney injury (AKI) and changes of blood urea, serum creatinine (Scr), blood uric acid, and estimated glomerular filtration rate (eGFR) in patients before and after Paxlovid treatment.Results:A total of 386 patients were included in the analysis, including 220 males (57.0%) and 166 females (43.0%), with a median age of 79 years. COVID-19 was classified as asymptomatic in 42 patients (10.9%), mild in 175 patients (45.4%), moderate in 126 patients (32.6%), severe in 34 patients (8.8%), and critical in 9 patients (2.3%). The renal insufficiency was mild in 246 patients (63.7%), moderate in 110 patients (28.5%), and severe in 30 patients (7.8%). Among 386 patients, 16 (4.1%) developed AKI during Paxlovid treatment or within 48 hours after withdrawal, 5 (1.3%) of which were judged to be related to Paxlovid. The 5 patients aged 70 years and above, and all used nephrotoxic drugs. After Paxlovid treatment, the blood urea, Scr, blood uric acid, and eGFR in the 386 patients were all improved compared to before, and the differences were statistically significant [Scr: (133.8±9.3) μmol/L vs. (111.7±6.6) μmol/L; blood uric acid: (335.9±7.1) μmol/L vs. (291.9±5.8) μmol/L; eGFR: (63.4±1.1) ml/(min·1.73 m 2) vs. (69.1±1.2) ml/(min·1.73 m 2); all P<0.05]. Conclusions:The overall safety of Paxlovid treatment for COVID-19 in patients with renal insufficiency is good, and it has no significant impact on the renal function in the vast majority of patients. However, for elderly people aged 70 years and above, especially for those who have combination medications of nephrotoxic drugs, the occurrence of AKI should still be vigilant.
5.Clinical observation of the effect of nirmatrelvir/ritonavir on renal function in patients with coronavirus disease 2019 and renal insufficiency
Jin′e PENG ; Hui LIU ; Jianying XIA ; Shuo WANG ; Hanqiu ZHAN
Adverse Drug Reactions Journal 2024;26(5):275-279
Objective:To explore the effect of nirmatrelvir/ritonavir (Paxlovid) on renal function in patients with coronavirus disease 2019 (COVID-19) and renal insufficiency.Methods:Clinical data of renal insufficiency patients with COVID-19, who were hospitalized at Beijing Ditan Hospital, Capital Medical University from March 23, 2022 to April 30, 2023 and received Paxlovid treatment, were collected. A retrospective analysis was conducted on the incidence of Paxlovid-related acute kidney injury (AKI) and changes of blood urea, serum creatinine (Scr), blood uric acid, and estimated glomerular filtration rate (eGFR) in patients before and after Paxlovid treatment.Results:A total of 386 patients were included in the analysis, including 220 males (57.0%) and 166 females (43.0%), with a median age of 79 years. COVID-19 was classified as asymptomatic in 42 patients (10.9%), mild in 175 patients (45.4%), moderate in 126 patients (32.6%), severe in 34 patients (8.8%), and critical in 9 patients (2.3%). The renal insufficiency was mild in 246 patients (63.7%), moderate in 110 patients (28.5%), and severe in 30 patients (7.8%). Among 386 patients, 16 (4.1%) developed AKI during Paxlovid treatment or within 48 hours after withdrawal, 5 (1.3%) of which were judged to be related to Paxlovid. The 5 patients aged 70 years and above, and all used nephrotoxic drugs. After Paxlovid treatment, the blood urea, Scr, blood uric acid, and eGFR in the 386 patients were all improved compared to before, and the differences were statistically significant [Scr: (133.8±9.3) μmol/L vs. (111.7±6.6) μmol/L; blood uric acid: (335.9±7.1) μmol/L vs. (291.9±5.8) μmol/L; eGFR: (63.4±1.1) ml/(min·1.73 m 2) vs. (69.1±1.2) ml/(min·1.73 m 2); all P<0.05]. Conclusions:The overall safety of Paxlovid treatment for COVID-19 in patients with renal insufficiency is good, and it has no significant impact on the renal function in the vast majority of patients. However, for elderly people aged 70 years and above, especially for those who have combination medications of nephrotoxic drugs, the occurrence of AKI should still be vigilant.
6.Gene characteristics analysis on Sapovirus from diarrhea cases in Beijing, 2019
Shuang LI ; Zhiyong GAO ; Weihong LI ; Yi TIAN ; Baiwei LIU ; Lingyu SHEN ; Hanqiu YAN ; Lei JIA ; Daitao ZHANG ; Quanyi WANG
Chinese Journal of Epidemiology 2023;44(11):1787-1794
Objective:To understand the gene characteristics of Sapovirus from diarrhea cases in diarrhoeal disease clinics in Beijing.Methods:In 2019, stool samples were collected from diarrhea cases in diarrhoeal disease clinics in Beijing. The samples were used for the detection of nucleic acid of Sapovirus with real-time RT-PCR. Different RT-PCR methods were used for the partial gene segment amplification in the capsid protein VP1 region and the polymerase RdRp region, and sequencing was conducted for amplified positive products. The sequences were aligned with software BioEdit 7.0.9.0 and analyzed with software Mega 6.06.Results:The overall detection rate of Sapovirus was 2.89% (44/1 522), the detection rate in children under 5 years old was 3.34% (18/539) and 2.64% (26/983) in children aged ≥5 years. The capsid protein VP1 region was sequenced in 23 strains belonging to 8 genotypes (GⅠ.2 had 6 strains, GⅠ.1 and GⅡ.3 had 5 strains, respectively, GⅠ.3 and GⅡ.5 had 2 strains, respectively, GⅠ.5, GⅡ.1 and GⅣ.1 had 1 strain, respectively). A total of 16 strains were detected in the cases aged ≥5 years, and the proportion of GⅠ.2 was highest (37.50%, 6/16), and 7 strains were detected in the cases under 5 years old, the proportions of GⅠ.1 and GⅡ.3 were highest (both 42.86%, 3/7); The internal similarity of each genotype was 95.5%-100.0%, and the similarity with the 51 reference strains of human or sewage sources in different years and different countries was 92.2%-100.0%. The polymerase RdRp region was sequenced in 25 strains belonging to 8 genotypes (GⅡ.P3 had 9 strains, GⅠ.P3 had 4 strains, GⅠ.P1, GⅠ.P2 and GⅡ.P1 had 3 strains, respectively, GⅠ.P5, GⅡ.P5 and GⅣ.P1 had 1 strain, respectively). Fifteen strains were detected in the cases aged ≥5 years, and GⅡ.P3 had the highest proportion (40.00%, 6/15). Ten strains were detected in the cases under 5 years old, and the proportions of GⅠ. P1, GⅡ.P1 and GⅡ.P3 were highest (all 30.00%, 3/10); The internal similarity of each genotype was 94.0%-100.0%, and the similarity with the 39 reference strains of human or sewage sources in different years and different countries was 90.2%-99.1%.Conclusions:Sapovirus is one of the pathogens among diarrhea cases in Beijing. The main genome is GⅠ and GⅡ, and the genotypes are diverse and dispersed. The main genotypes of diarrhea cases in people aged ≥5 years and less than 5 years are different.
7.Safety analysis of nirmatrelvir/ritonavir in the treatment of coronavirus disease 2019
Jin'e PENG ; Hui LIU ; Xiao LI ; Lijun WANG ; Shuo WANG ; Haofan SU ; Hanqiu ZHAN ; Wei ZHANG
Adverse Drug Reactions Journal 2023;25(1):11-16
Objective:To explore the safety of nirmatrelvir/ritonavir (Paxlovid) in the treatment of coronavirus disease 2019 (COVID-19).Methods:Medical records of adult patients with COVID-19 who were hospitalized and treated with Paxlovid in Beijing Ditan Hospital, Capital Medical University between March 23 and May 31, 2022 were collected through the hospital electronic medical record system. The occurrence (time of occurrence, clinical manifestations, severity, etc.) and outcomes of adverse reactions were analyzed retrospectively and the clinical characteristics of patients with or without adverse reactions were compared. Paxlovid was administered orally with nirmatrelvir 300 mg and ritonavir 100 mg every 12 hours for 5 consecutive days.Results:Three hundred and sixty-four patients were entered in the analysis, including 200 males (54.9%) and 164 females (45.1%), with a median age of 60 (19, 92) years. The incidence of adverse reactions of Paxlovid was 13.2% (48/364), and the adverse reactions occurred 1 to 7 days after taking Paxlovid. Among the 48 patients, 37 patients had digestive system symptoms (mainly manifested as diarrhea in 17 patients, bitter mouth in 14 patients, etc.), 7 patients had nervous system symptoms (dizziness in 5 patients, headache in 2 patients), 4 patients had respiratory system symptoms (pharyngalgia in 3 patients, pharyngeal itching in 1 patient), 2 patients had kidney injury, 1 patient had elevated blood uric acid, 1 patient had myalgia, and 1 patient had rash. Of them, 2 patients had digestive and neurological symptoms at the same time, 1 patient had digestive and respiratory symptoms at the same time, and 1 patient had digestive, neurological, and respiratory symptoms at the same time. The severity of adverse reactions was grade 1 in 33 patients (68.8%) and grade 2 in 15 patients (31.2%), and no serious adverse reactions of grade 3 and above occurred. All patients completed 5 days of treatment except 1 patient who discontinued the drug because of intolerance to grade 2 digestive symptoms (nausea and bitter mouth). There were no significant differences in gender, age, body mass index, smoking status, underlying diseases, and COVID-19 clinical classification between the patients with and without adverse reactions (all P>0.05). Conclusions:Paxlovid has a good safety in the treatment of COVID-19. The main adverse reaction is digestive system symptoms, mainly diarrhea and bitter mouth. Most of the symptoms are mild and the patient′s tolerance is good.
8.Safety analysis of nirmatrelvir/ritonavir in the treatment of coronavirus disease 2019
Jin'e PENG ; Hui LIU ; Xiao LI ; Lijun WANG ; Shuo WANG ; Haofan SU ; Hanqiu ZHAN ; Wei ZHANG
Adverse Drug Reactions Journal 2023;25(1):11-16
Objective:To explore the safety of nirmatrelvir/ritonavir (Paxlovid) in the treatment of coronavirus disease 2019 (COVID-19).Methods:Medical records of adult patients with COVID-19 who were hospitalized and treated with Paxlovid in Beijing Ditan Hospital, Capital Medical University between March 23 and May 31, 2022 were collected through the hospital electronic medical record system. The occurrence (time of occurrence, clinical manifestations, severity, etc.) and outcomes of adverse reactions were analyzed retrospectively and the clinical characteristics of patients with or without adverse reactions were compared. Paxlovid was administered orally with nirmatrelvir 300 mg and ritonavir 100 mg every 12 hours for 5 consecutive days.Results:Three hundred and sixty-four patients were entered in the analysis, including 200 males (54.9%) and 164 females (45.1%), with a median age of 60 (19, 92) years. The incidence of adverse reactions of Paxlovid was 13.2% (48/364), and the adverse reactions occurred 1 to 7 days after taking Paxlovid. Among the 48 patients, 37 patients had digestive system symptoms (mainly manifested as diarrhea in 17 patients, bitter mouth in 14 patients, etc.), 7 patients had nervous system symptoms (dizziness in 5 patients, headache in 2 patients), 4 patients had respiratory system symptoms (pharyngalgia in 3 patients, pharyngeal itching in 1 patient), 2 patients had kidney injury, 1 patient had elevated blood uric acid, 1 patient had myalgia, and 1 patient had rash. Of them, 2 patients had digestive and neurological symptoms at the same time, 1 patient had digestive and respiratory symptoms at the same time, and 1 patient had digestive, neurological, and respiratory symptoms at the same time. The severity of adverse reactions was grade 1 in 33 patients (68.8%) and grade 2 in 15 patients (31.2%), and no serious adverse reactions of grade 3 and above occurred. All patients completed 5 days of treatment except 1 patient who discontinued the drug because of intolerance to grade 2 digestive symptoms (nausea and bitter mouth). There were no significant differences in gender, age, body mass index, smoking status, underlying diseases, and COVID-19 clinical classification between the patients with and without adverse reactions (all P>0.05). Conclusions:Paxlovid has a good safety in the treatment of COVID-19. The main adverse reaction is digestive system symptoms, mainly diarrhea and bitter mouth. Most of the symptoms are mild and the patient′s tolerance is good.
9.Clinical characteristics of diarrhea among children infected with rotavirus in Beijing, 2011 to 2018
Yi TIAN ; Hanqiu YAN ; Weihong LI ; Baiwei LIU ; Xiaona WU ; Lei JIA ; Quanyi WANG ; Zhiyong GAO
Chinese Journal of Experimental and Clinical Virology 2022;36(6):685-690
Objective:To provide evidence for clinical diagnosis, prevention and control of group A rotavirus (RVA) diarrhea, the clinical characteristics of RVA diarrhea in children in Beijing from 2011 to 2018 were analyzed.Methods:From January 2011 to December 2018, 4 819 stool samples from children under 5 years old with diarrhea were collected monthly from 3 hospitals in Beijing. General information, clinical characteristics and other information of children were collected. RVA was detected by enzyme-linked immunosorbent assay (ELISA), genotype was identified by multiple semi-nested RT-PCR. The Vesikari clinical severity score was used to define the severity of diarrhea in children. Dichotomous unconditional logistic regression was used to analyze clinical symptoms and other differences between RVA positive and negative cases. Chi-square and Fisher direct probability tests were used to compare the composition among different groups.Results:A total of 4 819 fecal samples were collected, 953 were positive for RVA, the positive detection rate was 19.78%. The positive rate of RVA was high in the younger age group, and the incidence was high in winter and spring. RVA-positive children had more risk on diarrhea ≥5 times a day, vomiting symptoms, fever, mild dehydration, and Vesikari score ≥11. The positive rate of RVA in watery stool samples (26.13%, 214/819) and infectious diarrhea cases (42.20%, 265/628) was the highest respectively. There were no significant differences in clinical symptoms, clinical diagnoses and fecal traits among children with different RVA genotypes.Conclusions:The clinical symptoms of RVA diarrhea were severe in children. RVA genotype did not affect the clinical symptoms. Stool traits (watery stools) and Vesikari score can assist physicians in diagnosing RVA diarrhea.
10.Investigation on Norovirus prevalence in catering companies and train station in Beijing during non-epidemic season in 2019
Yang ZHENG ; Lei JIA ; Baiwei LIU ; Zhiyong GAO ; Yi TIAN ; Xiaoli WANG ; Hanqiu YAN ; Quanyi WANG
Chinese Journal of Preventive Medicine 2021;55(7):875-878
Objective:To study the prevalence of Norovirus infection among kitchen workers in Beijing, and the contamination status of Norovirus in catering companies and train station.Methods:A cross-sectional survey was conducted to collect anal swab specimens and environmental specimens from catering companies in 16 districts of Beijing and in 3 big train stations. Norovirus nucleic acid was detected by fluorescence quantitative PCR. The contamination status of Norovirus in the environment and the asymptomatic infection status of kitchen workers was analyzed in this study.Results:A total of 650 catering companies were investigated. 1 302 anal swabs or stool specimens and 2 600 environmental swabs were collected and tested. Among the 644 catering companies out of train stations, 1 290 anal swabs or stool specimens and 2 576 environmental swabs were collected and tested. The asymptomatic infection rate of Norovirus was 0.85% (11/1 290) among kitchen workers of the catering companies out of the train stations, while the positive rate of norovirus contamination in the environment was 0.04% (1/2 576). Norovirus was not detected in the specimens collected from the kitchen workers and the environment of the catering companies in train stations.Conclusion:During the non-epidemic season of Norovirus in 2019, the infection rate of Norovirus among kitchen workers in Beijing is low, and the environment is contaminated by Norovirus.

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