Review
Virology
Karolina Akinosoglou, Georgios Schinas, Charalambos Gogos
Summary: The protease inhibitor nirmatrelvir coupled with ritonavir has shown promise in preventing disease progression in high-risk COVID-19 patients. Real-world data support the efficacy and safety of this oral antiviral agent, although potential resistance issues need further investigation.
Article
Pharmacology & Pharmacy
Jiayue Lu, Hong Cai, Yujun Hao, Zhang Lin, Shang Liu, Yaping Zhan, Li Ding, Meilan Huang, Zhenyuan Li, Lan Xu, Xiujuan Yan, Li Yang, He Zhang, Wei Zhang, Li Zhao, Junli Zhao, Ting Wang, Leyi Gu
Summary: This study aims to evaluate the minimum plasma concentration and safety of different doses of nirmatrelvir/ritonavir in hemodialysis patients with mild COVID-19. The results suggest that both doses of nirmatrelvir/ritonavir may be excessive for hemodialysis patients, as nearly half of the patients experienced drug-related adverse events. Additionally, the medication group did not show a significant advantage in the time of viral elimination.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Infectious Diseases
Yuan-Pin Hung, Jen-Chieh Lee, Chun-Wei Chiu, Ching-Chi Lee, Pei-Jane Tsai, I-Lin Hsu, Wen-Chien Ko
Summary: Nirmatrelvir/ritonavir is an effective and safe antiviral drug that inhibits the main protease of SARS-CoV-2. It shows promising antiviral effect against recent coronavirus mutants, but its effectiveness against future variants needs to be monitored.
Letter
Medicine, General & Internal
Annaliesa S. Anderson, Patrick Caubel, James M. Rusnak
Summary: Viral load rebound of SARS-CoV-2 has been reported after a 5-day treatment course of nirmatrelvir-ritonavir. Investigators have found similar results in terms of viral load rebound between nirmatrelvir-ritonavir and placebo among high-risk patients.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Infectious Diseases
Xiang Zhao, Yuan Cheng, Meng Zhang, Bianba Qianda, Baima Zhouma, Bianba Yangzhen, Yao Zheng, Shuo Zhang, Huiying Zhao
Summary: This study compared the efficacy of azvudine and nirmatrelvir-ritonavir in COVID-19 patients. The results showed that azvudine was generally as effective as nirmatrelvir-ritonavir, but nirmatrelvir-ritonavir could suppress the virus more rapidly in mild cases. This suggests that azvudine could be an effective therapy for COVID-19 in patients who cannot be treated with nirmatrelvir-ritonavir.
INFECTION AND DRUG RESISTANCE
(2023)
Article
Immunology
Julie Boucau, Rockib Uddin, Caitlin Marino, James Regan, James P. Flynn, Manish C. Choudhary, Geoffrey Chen, Ashley M. Stuckwisch, Josh Mathews, May Y. Liew, Arshdeep Singh, Zahra Reynolds, Surabhi L. Iyer, Grace C. Chamberlin, Tammy D. Vyas, Jatin M. Vyas, Sarah E. Turbett, Jonathan Z. Li, Jacob E. Lemieux, Amy K. Barczak, Mark J. Siedner
Summary: We enrolled 7 individuals who experienced recurrent symptoms or antigen test conversion after treatment with nirmatrelvir-ritonavir. High viral loads were detected after rebound, lasting a median of 17 days after initial diagnosis. Three individuals had culturable virus for up to 16 days after initial diagnosis. No known resistance-associated mutations were found.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Pharmacology & Pharmacy
Sima S. Toussi, Joel Michael Neutel, Jesus Navarro, Richard Alfred Preston, Haihong Shi, Olga Kavetska, Robert R. LaBadie, Michael Binks, Phylinda L. S. Chan, Neil Demers, Brian Corrigan, Bharat Damle
Summary: This study evaluated the effects of renal impairment on the pharmacokinetics, safety, and tolerability of nirmatrelvir/ritonavir. The results showed that the exposure of nirmatrelvir increased with increasing renal impairment. However, the treatment with nirmatrelvir/ritonavir demonstrated an acceptable safety profile, and a dose reduction recommendation was made for patients with moderate renal impairment.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Medicine, General & Internal
Haein Kim, Jeong-Sun Yang, Jae-Hoon Ko, Myungsun Lee, Joo-Yeon Lee, Sehee Park, Jun-Won Kim, Younmin Shin, Jung-Min Lee, Yoo Jin Na, Byoung Kwon Park, Hyungjin Kim, Young Ho Lee, Jinyoung Yang, Kyungmin Huh, Sun Young Cho, Cheol-In Kang, Doo Ryeon Chung, Kyong Ran Peck
Summary: Nirmatrelvir/ritonavir treatment effectively reduces viral loads of SARS-CoV-2 Omicron variants but does not decrease the duration of viable virus shedding.
FRONTIERS IN MEDICINE
(2022)
Article
Infectious Diseases
Mario Cruciani, Ilaria Pati, Francesca Masiello, Simonetta Pupella, Vincenzo De Angelis
Summary: Nirmatrelvir/ritonavir has shown to reduce mortality and hospital admission rates in COVID-19 patients without increasing the occurrence of overall and serious adverse events, based on low to moderate certainty of evidence from systematic reviews. The methodological quality of the systematic reviews was assessed to be high, providing confidence in the generated results.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Immunology
Sarju Ganatra, Sourbha S. Dani, Javaria Ahmad, Ashish Kumar, Jui Shah, George M. Abraham, Daniel P. McQuillen, Robert M. Wachter, Paul E. Sax
Summary: In this observational analysis, treatment with nirmatrelvir plus ritonavir in nonhospitalized vaccinated patients at high risk of disease progression was associated with a significantly reduced likelihood of emergency room visits, hospitalization, or death between days 10 and 30, with no apparent increase in serious complications.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Microbiology
Robert L. Atmar, Natalie Finch
Summary: SARS-CoV-2 has caused a global pandemic for the past 2 years, resulting in high morbidity and mortality worldwide. Although only nonspecific treatments were available initially, two oral antivirals have recently been approved for emergency use in the treatment of mild to moderate COVID-19. These drugs inhibit viral replication and have shown significant reduction in severe outcomes when initiated early in at-risk patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Ziteng Wang, Eric Chun Yong Chan
Summary: This study simulated the potential drug-drug interactions of ritonavir with anticoagulants rivaroxaban and warfarin in patients with COVID-19, using physiologically-based pharmacokinetic modeling. It was found that nirmatrelvir/ritonavir treatment could elevate rivaroxaban concentrations, especially in geriatric subjects with renal impairment, while lowering warfarin concentrations. Longer monitoring of warfarin's international normalized ratio (INR) becomes important in this context.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Medicine, Research & Experimental
Seyed Mohammad Reza Hashemian, Amirhossein Sheida, Mohammad Taghizadieh, Mohammad Yousef Memar, Michael R. Hamblin, Hossein Bannazadeh Baghi, Javid Sadri Nahand, Zatollah Asemi, Hamed Mirzaei
Summary: Due to the lack of effective therapies for COVID-19, patients have to rely on supportive and nonspecific treatments. Certain proteins of SARS-CoV-2, such as 3 C-like protease (3CLpro) and major protease (Mpro), have been identified as potential targets for antiviral drugs. Nirmatrelvir, combined with ritonavir, has shown potent antiviral activity against SARS-CoV-2 variants, but there are still uncertainties regarding their efficacy, safety, and side effects.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Medicine, General & Internal
Stefanie Reis, Maria-Inti Metzendorf, Rebecca Kuehn, Maria Popp, Ildiko Gagyor, Peter Kranke, Patrick Meybohm, Nicole Skoetz, Stephanie Weibel
Summary: Nirmatrelvir/ritonavir may reduce mortality and hospitalization in outpatient settings with mild COVID-19, but may increase some treatment-related adverse events. Ethnicity may influence treatment effectiveness in the equity aspect. However, there is currently no available evidence for nirmatrelvir/ritonavir in treating hospitalized patients or preventing SARS-CoV-2 infection.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2022)
Article
Medicine, General & Internal
Jennifer Hammond, Heidi Leister-Tebbe, Annie Gardner, Paula Abreu, Weihang Bao, Wayne Wisemandle, MaryLynn Baniecki, Victoria M. Hendrick, Bharat Damle, Abraham Simon-Campos, Rienk Pypstra, James M. Rusnak
Summary: In high-risk, unvaccinated adults, treatment of Covid-19 with nirmatrelvir plus ritonavir can significantly reduce the risk of hospitalization and death, with good safety profile.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Letter
Gastroenterology & Hepatology
Zhujun Cao, Honglian Gui, Zike Sheng, Haiguang Xin, Qing Xie
Article
Immunology
Yan Huang, Qinyi Gan, Rongtao Lai, Weijing Wang, Simin Guo, Zike Sheng, Lu Chen, Qing Guo, Wei Cai, Hui Wang, Gangde Zhao, Zhujun Cao, Qing Xie
Summary: Concurrent non-alcoholic fatty liver disease (NAFLD) is common in chronic hepatitis B (CHB) patients, and non-alcoholic steatohepatitis (NASH) is an independent risk factor potentiating significant fibrosis by 2.53-fold and severe fibrosis by 1.83-fold. Routine assessment of co-existing NAFLD or NASH is important while coping with chronic HBV infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Infectious Diseases
Zhujun Cao, Chenxi Zhang, Shuang Zhao, Zike Sheng, Xiaogang Xiang, Ruokun Li, Zhuping Qian, Yinling Wang, Bin Chen, Ziqiang Li, Yuhan Liu, Baoyan An, Huijuan Zhou, Wei Cai, Hui Wang, Honglian Gui, Haiguang Xin, Qing Xie
Summary: The COVID-19 vaccination rate is low in patients with decompensated cirrhosis in eastern China, particularly in those with a history of ACLF or hepatic encephalopathy and liver transplantation recipients. Factors associated with remaining unvaccinated include the experience of hepatic encephalopathy or ACLF and post-liver transplantation status. Vaccination against COVID-19 is safe in this population.
INFECTIOUS DISEASES OF POVERTY
(2022)
Letter
Gastroenterology & Hepatology
Nahum Mendez-Sanchez, Elisabetta Bugianesi, Robert G. Gish, Frank Lammert, Herbert Tilg, Mindie H. Nguyen, Shiv K. Sarin, Nuria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Takumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C. Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-Francois Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero-Gomez, Mohammed Eslam
LANCET GASTROENTEROLOGY & HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Liu Chuan, Cao Zhujun, Yan Huadong, Wong Yu Jun, Xie Qing, Masashi Hirooka, Hirayuki Enomoto, Tae Hyung Kim, Amr Shaaban Hanafy, Liu Yanna, Huang Yifei, Li Xiaoguo, Kang Ning, Yohei Koizumi, Yoichi Hiasa, Takashi Nishimura, Hiroko Iijima, Young Kul Jung, Hyung Joon Yim, Guo Ying, Zhang Linpeng, Ma Jianzhong, Manoj Kumar, Ankur Jindal, Kok Ban Teh, Shiv Kumar Sarin, Qi Xiaolong
Summary: This study developed a new score (SAVE score) that accurately predicts the risk of hepatic decompensation in cACLD patients and also accurately predicts clinically significant portal hypertension.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2022)
Letter
Infectious Diseases
Fangfang Sun, Yanwei Lin, Xiaodong Wang, Yuan Gao, Shuang Ye
LANCET INFECTIOUS DISEASES
(2022)
Article
Biochemical Research Methods
Zhe LI, Pengbo He, Yuqing Xu, Yuxiao Deng, Yuvan Gao, Sung -liang Chen
Summary: This study demonstrates the noninvasive observation of inflammation-related vascular leakage using photoacoustic microscopy (PAM) in mice. A model combining LPS application and EB injection on mouse ears was developed for the identification and evaluation of early vascular leakage. The results show the potential of PAM in clinical sepsis diagnosis and management.
BIOMEDICAL OPTICS EXPRESS
(2022)
Article
Gastroenterology & Hepatology
Qinyi Gan, Yan Huang, Chuanwu Zhu, Shuang Zhao, Haoshuang Fu, Minghao Cai, Jiexiao Wang, Chenxi Zhang, Simin Guo, Zhujun Cao, Qing Xie
Summary: This study aimed to evaluate the utility of serum qHBsAg in detecting histological abnormalities in HBeAg-negative chronic HBV infection patients. The results showed that qHBsAg level was associated with the severity of hepatic inflammation and fibrosis, and it was identified as an independent predictor along with age, AST level, and family history of HBV infection.
CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Letter
Critical Care Medicine
Zhe Li, Yuan Gao, Zhanqi Zhao
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Infectious Diseases
Honglian Gui, Zhenglan Zhang, Bin Chen, Yaoxing Chen, Yue Wang, Zhuo Long, Chuanwu Zhu, Yinling Wang, Zhujun Cao, Qing Xie
Summary: This study aimed to determine the predictors of prolonged viral RNA shedding in patients with non-severe COVID-19 and construct a nomogram to predict patients at risk of 14-day PCR conversion failure. The study found that older age, increasing comorbidities, incomplete vaccinations, and lack of antiviral therapy are risk factors for persistent infection with Omicron variant for > 14 days. A nomogram based on these predictors could be used as a prediction tool to guide treatment and isolation strategies.
INFECTIOUS DISEASES OF POVERTY
(2023)
Article
Biochemistry & Molecular Biology
Ri Tang, Shuya Mei, Qiaoyi Xu, Jinhua Feng, Yang Zhou, Shunpeng Xing, Zhengyu He, Yuan Gao
Summary: Recent clinical research has found that mechanical ventilation (MV) can lead to pulmonary fibrosis, known as mechanical ventilation-induced pulmonary fibrosis (MVPF). This study investigates the potential mechanism of MVPF using a mouse model and an alveolar epithelial cell cyclic strain model, revealing that the ASK1-ER stress pathway plays a crucial role in the release of fibrotic extracellular vesicles (EVs) from alveolar epithelial cells, which contribute to fibroblast activation and the initiation of pulmonary fibrosis during MV.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Medicine, Research & Experimental
Shuya Mei, Qiaoyi Xu, Yue Hu, Ri Tang, Jinhua Feng, Yang Zhou, Shunpeng Xing, Yuan Gao, Zhengyu He
Summary: This study found that the integrin beta 3-PKM2 pathway-mediated aerobic glycolysis is involved in mechanical ventilation-induced pulmonary fibrosis. Inhibiting aerobic glycolysis targeting the integrin beta 3-PKM2 pathway may be a promising treatment for mechanical ventilation-induced pulmonary fibrosis.
Letter
Gastroenterology & Hepatology
Zhujun Cao, Qing Xie