BACKGROUND Since its initial detection in 2019,coronavirus disease 2019(COVID-19)pneumonia has rapidly spread throughout the world in a global pandemic.However,reports of COVID-19 pneumonia among patients following ki...BACKGROUND Since its initial detection in 2019,coronavirus disease 2019(COVID-19)pneumonia has rapidly spread throughout the world in a global pandemic.However,reports of COVID-19 pneumonia among patients following kidney transplantation have been limited and no uniform treatment guidelines for these patients have yet to be established.CASE SUMMARY Here,we report the case of a 39-year-old patient recovering from kidney transplantation who contracted perioperative COVID-19 pneumonia that was successfully controlled with oral paxlovid and a single intravenous drip infusion of tocilizumab following the discontinuation of immunosuppressive drugs.CONCLUSION Given the rapid spread of severe acute respiratory syndrome coronavirus 2 infections,clinicians should be aware of the potential for more cases of COVID-19 among patients following kidney transplantation and be familiar with appropriate treatment options and likely clinical outcomes.展开更多
BACKGROUND According to the population statistics in 2023,there were 110000 people aged over 100 years in China,and the experience of using Paxlovid(nirmatrelvir/ritonavir)for centenarians is particularly valuable.Thi...BACKGROUND According to the population statistics in 2023,there were 110000 people aged over 100 years in China,and the experience of using Paxlovid(nirmatrelvir/ritonavir)for centenarians is particularly valuable.This article reports our experience of using Paxlovid in a centenarian with the novel coronavirus disease 2019(COVID-19)infection.CASE SUMMARY A 103-year-old female with mild COVID-19 and renal insufficiency was given sufficient Paxlovid for 2 days and a half dose for 3 days.During treatment,the patient was complicated with lung infection and heart failure,and nucleic acid remained positive.After expert consultation,a full dose of Paxlovid was given again on the 9th day of admission for 2 days and a half dose for 3 days.Meanwhile,anti-heart failure and antibiotics were administered;the heart failure and pulmonary infection were improved.Finally,on the 33^(th) day of admission,nucleic acid turned negative,body temperature returned to normal,cough and sputum,fatigue,poor appetite and other symptoms basically improved.The patient was given Paxlovid via nasal feeding for 2 courses without deterioration of liver and kidney function,diarrhea,nausea and vomiting,myalgia,chest tightness and other side effects,and was discharged from hospital with good recovery.CONCLUSION This case suggests that Paxlovid can be used cautiously in centenarians with renal insufficiency and two courses of treatment can be considered in patients with persistent positive nucleic acid.展开更多
Paxlovid is a nirmatrelvir(NMV)and ritonavir(RTV)co-packaged medication used for the treatment of coronavirus disease 2019(COVID-19).The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster.Our wor...Paxlovid is a nirmatrelvir(NMV)and ritonavir(RTV)co-packaged medication used for the treatment of coronavirus disease 2019(COVID-19).The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster.Our work aimed to investigate the drug/herb-drug interactions associated with Paxlovid and provide mechanism-based guidance for the clinical use of Paxlovid.By using recombinant human cytochrome P450s(CYPs),we confirmed that CYP3A4 and 3A5 are the major enzymes responsible for NMV metabolism.The role of CYP3A in Paxlovid metabolism were further verified in Cyp3a-null mice,which showed that the deficiency of CYP3A significantly suppressed the metabolism of NMV and RTV.Pregnane X receptor(PXR)is a ligand-dependent transcription factor that upregulates CYP3A4/5 expression.We next explored the impact of drug-and herb-mediated PXR activation on Paxlovid metabolism in a transgenic mouse model expressing human PXR and CYP3A4/5.We found that PXR activation increased CYP3A4/5 expression,accelerated NMV metabolism,and reduced the systemic exposure of NMV.In summary,our work demonstrated that PXR activation can cause drug interactions with Paxlovid,suggesting that PXR-activating drugs and herbs should be used cautiously in COVID-19 patients receiving Paxlovid.展开更多
We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir(Paxlovid)therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Thirteen hemodia...We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir(Paxlovid)therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Thirteen hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30,2022,were recruited.Laboratory parameters and chest CT(computed tomography)imaging were analyzed.The treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days,whereas the control group included seven patients who received basic treatment.No serious adverse reactions or safety events were recorded.Four control patients progressed to moderate disease,and none in the treatment group showed progression of chest CT findings(P<0.05).Paxlovid therapy tended toward early viral clearance and low viral load on Day 8.Moreover,83.3%of the patients in the treatment group and 57.1%of the patients in the control group turned negative within 22 days.In the Paxlovid treatment group,we found significantly increased levels of lymphocytes(P=0.03)and eosinophils(P=0.02)and decreased levels of D-dimer on Day 8 compared with those on Day 1.Paxlovid therapy showed a potential therapeutic effect with good tolerance in hemodialysis patients.The optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.展开更多
目的评价先诺特韦/利托那韦对COVID-19老年衰弱患者的临床疗效与安全性。方法回顾性分析2023年3月至2024年8月于上饶市人民医院确诊COVID-19的老年衰弱住院患者,分为对照组应用奈玛特韦/利托那韦86例及试验组应用先诺特韦/利托那韦95例...目的评价先诺特韦/利托那韦对COVID-19老年衰弱患者的临床疗效与安全性。方法回顾性分析2023年3月至2024年8月于上饶市人民医院确诊COVID-19的老年衰弱住院患者,分为对照组应用奈玛特韦/利托那韦86例及试验组应用先诺特韦/利托那韦95例,比较两组症状恢复情况、临床疗效、及不良反应。结果181名受试者平均年龄72.61岁,其中轻度143例(79.01%),中度38例(20.99%);主要临床症状为发热167例(92.26%)、咳嗽164例(90.6%)、咳痰148例(81.76%)、疲劳120例(66.29%)等;多数患者合并基础疾病包括高血压88例(48.62%)、糖尿病61例(33.70%)、冠状动脉疾病80例(44.19%);试验组入院后接受先诺特韦/利托那韦治疗与接受奈玛特韦/利托那韦治疗后症状恢复时间分别为6.94 d vs 6.37 d(P=0.326),住院时间分别为14.12 d vs 13.35 d(P=0.239),住院时间Day 10、Day 14、Day 21百分比、重症率、高流量氧疗、机械通气差异均无统计学意义(P>0.05),两组患者治疗前后的白细胞、淋巴细胞计数、血红蛋白、血小板、C反应蛋白等差异均无统计学意义(P>0.05);安全性方面,两组患者耐受性良好,且没有患者因不良反应而过早停用,也未观察到严重的不良事件。结论本研究显示出,与奈玛特韦/利托那韦相比,先诺特韦/利托那韦亦可有效缓解COVID-19老年衰弱患者的临床症状,降低住院时间且安全性良好,为COVID-19老年衰弱患者提供了新的选择,但由于本研究仍存在诸多局限性,还需开展更高质量研究进一步验证。展开更多
基金Supported by Guiyang Science and Technology Program,No.2019-9-1-39.
文摘BACKGROUND Since its initial detection in 2019,coronavirus disease 2019(COVID-19)pneumonia has rapidly spread throughout the world in a global pandemic.However,reports of COVID-19 pneumonia among patients following kidney transplantation have been limited and no uniform treatment guidelines for these patients have yet to be established.CASE SUMMARY Here,we report the case of a 39-year-old patient recovering from kidney transplantation who contracted perioperative COVID-19 pneumonia that was successfully controlled with oral paxlovid and a single intravenous drip infusion of tocilizumab following the discontinuation of immunosuppressive drugs.CONCLUSION Given the rapid spread of severe acute respiratory syndrome coronavirus 2 infections,clinicians should be aware of the potential for more cases of COVID-19 among patients following kidney transplantation and be familiar with appropriate treatment options and likely clinical outcomes.
文摘BACKGROUND According to the population statistics in 2023,there were 110000 people aged over 100 years in China,and the experience of using Paxlovid(nirmatrelvir/ritonavir)for centenarians is particularly valuable.This article reports our experience of using Paxlovid in a centenarian with the novel coronavirus disease 2019(COVID-19)infection.CASE SUMMARY A 103-year-old female with mild COVID-19 and renal insufficiency was given sufficient Paxlovid for 2 days and a half dose for 3 days.During treatment,the patient was complicated with lung infection and heart failure,and nucleic acid remained positive.After expert consultation,a full dose of Paxlovid was given again on the 9th day of admission for 2 days and a half dose for 3 days.Meanwhile,anti-heart failure and antibiotics were administered;the heart failure and pulmonary infection were improved.Finally,on the 33^(th) day of admission,nucleic acid turned negative,body temperature returned to normal,cough and sputum,fatigue,poor appetite and other symptoms basically improved.The patient was given Paxlovid via nasal feeding for 2 courses without deterioration of liver and kidney function,diarrhea,nausea and vomiting,myalgia,chest tightness and other side effects,and was discharged from hospital with good recovery.CONCLUSION This case suggests that Paxlovid can be used cautiously in centenarians with renal insufficiency and two courses of treatment can be considered in patients with persistent positive nucleic acid.
基金supported in part by the National Center for Complementary and Integrative Health (R21AT011088,USA)the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK126875,USA)the National Institute of Allergy and Infectious Diseases (R01AI131983,USA)。
文摘Paxlovid is a nirmatrelvir(NMV)and ritonavir(RTV)co-packaged medication used for the treatment of coronavirus disease 2019(COVID-19).The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster.Our work aimed to investigate the drug/herb-drug interactions associated with Paxlovid and provide mechanism-based guidance for the clinical use of Paxlovid.By using recombinant human cytochrome P450s(CYPs),we confirmed that CYP3A4 and 3A5 are the major enzymes responsible for NMV metabolism.The role of CYP3A in Paxlovid metabolism were further verified in Cyp3a-null mice,which showed that the deficiency of CYP3A significantly suppressed the metabolism of NMV and RTV.Pregnane X receptor(PXR)is a ligand-dependent transcription factor that upregulates CYP3A4/5 expression.We next explored the impact of drug-and herb-mediated PXR activation on Paxlovid metabolism in a transgenic mouse model expressing human PXR and CYP3A4/5.We found that PXR activation increased CYP3A4/5 expression,accelerated NMV metabolism,and reduced the systemic exposure of NMV.In summary,our work demonstrated that PXR activation can cause drug interactions with Paxlovid,suggesting that PXR-activating drugs and herbs should be used cautiously in COVID-19 patients receiving Paxlovid.
基金Shanghai Key Laboratory of Emergency Prevention,Diagnosis and Treatment of Respiratory of Infectious Diseases(No.20dz2261100).
文摘We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir(Paxlovid)therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Thirteen hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30,2022,were recruited.Laboratory parameters and chest CT(computed tomography)imaging were analyzed.The treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days,whereas the control group included seven patients who received basic treatment.No serious adverse reactions or safety events were recorded.Four control patients progressed to moderate disease,and none in the treatment group showed progression of chest CT findings(P<0.05).Paxlovid therapy tended toward early viral clearance and low viral load on Day 8.Moreover,83.3%of the patients in the treatment group and 57.1%of the patients in the control group turned negative within 22 days.In the Paxlovid treatment group,we found significantly increased levels of lymphocytes(P=0.03)and eosinophils(P=0.02)and decreased levels of D-dimer on Day 8 compared with those on Day 1.Paxlovid therapy showed a potential therapeutic effect with good tolerance in hemodialysis patients.The optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.
文摘目的评价先诺特韦/利托那韦对COVID-19老年衰弱患者的临床疗效与安全性。方法回顾性分析2023年3月至2024年8月于上饶市人民医院确诊COVID-19的老年衰弱住院患者,分为对照组应用奈玛特韦/利托那韦86例及试验组应用先诺特韦/利托那韦95例,比较两组症状恢复情况、临床疗效、及不良反应。结果181名受试者平均年龄72.61岁,其中轻度143例(79.01%),中度38例(20.99%);主要临床症状为发热167例(92.26%)、咳嗽164例(90.6%)、咳痰148例(81.76%)、疲劳120例(66.29%)等;多数患者合并基础疾病包括高血压88例(48.62%)、糖尿病61例(33.70%)、冠状动脉疾病80例(44.19%);试验组入院后接受先诺特韦/利托那韦治疗与接受奈玛特韦/利托那韦治疗后症状恢复时间分别为6.94 d vs 6.37 d(P=0.326),住院时间分别为14.12 d vs 13.35 d(P=0.239),住院时间Day 10、Day 14、Day 21百分比、重症率、高流量氧疗、机械通气差异均无统计学意义(P>0.05),两组患者治疗前后的白细胞、淋巴细胞计数、血红蛋白、血小板、C反应蛋白等差异均无统计学意义(P>0.05);安全性方面,两组患者耐受性良好,且没有患者因不良反应而过早停用,也未观察到严重的不良事件。结论本研究显示出,与奈玛特韦/利托那韦相比,先诺特韦/利托那韦亦可有效缓解COVID-19老年衰弱患者的临床症状,降低住院时间且安全性良好,为COVID-19老年衰弱患者提供了新的选择,但由于本研究仍存在诸多局限性,还需开展更高质量研究进一步验证。
