Tag: Paxlovid

Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C

Abstract:

Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC.

We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,461 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence.

Our primary outcome measure was a PASC computable phenotype. Secondary outcomes were the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.99, 95% confidence interval [CI] 0.96-1.01). However, its effect varied across the cognitive (RR = 0.85, 95% CI 0.79-0.90), fatigue (RR = 0.93, 95% CI 0.89-0.96), and respiratory (RR = 0.99, 95% CI 0.95-1.02) symptom clusters, suggesting that Paxlovid treatment may help prevent post-acute cognitive and fatigue symptoms more than others.

Source: Alexander Preiss, Abhishek Bhatia, Chengxi Zang, Leyna V. Aragon, John M. Baratta, Monika Baskaran, Frank Blancero, M. Daniel Brannock, Robert F. Chew, Iván Díaz, Megan Fitzgerald, Elizabeth P. Kelly, Andrea Zhou, Mark G. Weiner, Thomas W. Carton, Fei Wang, Rainu Kaushal, Christopher G. Chute, Melissa Haendel, Richard Moffitt, Emily Pfaff. Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C. medRxiv 2024.01.20.24301525; doi: https://doi.org/10.1101/2024.01.20.24301525 https://www.medrxiv.org/content/10.1101/2024.01.20.24301525v1.full-text (Full text)

The effect of nirmatrelvir-ritonavir on the long-term risk of neuropsychiatric sequelae following COVID-19

Abstract:

The retrospective cohort was conducted to assess the effect of nirmatrelvir-ritonavir (NMV-r) on the long-term risk of neuropsychiatric sequela following COVID-19. TriNetX research network was used to identify nonhospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 infection or were diagnosed with COVID-19 between March 1, 2020 and July 1, 2022. Further propensity score matching method was used to create two matched cohorts with and without receiving NMV-r.

The primary outcome was the incidence of neuropsychiatric sequela within a 90-day to 1-year period following a diagnosis of COVID-19. After screening 119 494 527 electronic health records, two matched cohorts of each 27 194 patients were identified. During the follow-up period, the NMV-r group demonstrated a reduced risk of any neuropsychiatric sequelae compared to the control group (odds ratio [OR], 0.634; 95% confidence interval [CI], 0.604-0.667).

In comparison with the control group, the patient treated with NMV-r exhibited a markedly diminished risk of developing neurocognitive sequela (OR, 0.377; 95% CI, 0.325-0.439) and psychiatric sequela (OR, 0.629; 95% CI, 0.593-0.666). In addition, patients treated with NMV-r had a significantly reduced risk of developing dementia (OR, 0.365; 95% CI, 0.255-0.522), depression (OR, 0.555; 95% CI, 0.503-0.612), insomnia (OR, 0.582; 95% CI, 0.508-0.668) and anxiety disorder (OR, 0.645 95% CI, 0.600-0.692). Moreover, the beneficial effect of NMV-r on the neuropsychiatric sequelae was observed across further subgroup analyses.

Among nonhospitalized COVID-19 patients, who at risk of disease progression, the use of NMV-r is associated with a reduction in the long-term risk of neuropsychiatric sequela, including dementia, depression, insomnia and anxiety disorder. It may be necessary to re-evaluate the use of NMV-r, as a preventive measure to reduce the risk of severe acute disease and post-acute adverse mental health outcomes.

Source: Liu TH, Wu JY, Huang PY, Tsai YW, Lai CC. The effect of nirmatrelvir-ritonavir on the long-term risk of neuropsychiatric sequelae following COVID-19. J Med Virol. 2023 Jul;95(7):e28951. doi: 10.1002/jmv.28951. PMID: 37436873. https://pubmed.ncbi.nlm.nih.gov/37436873/

Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis

Abstract:

Background: The COVID-19 pandemic has become a huge threat to human health, infecting millions of people worldwide and causing enormous economic losses. Many novel small molecule drugs have been developed to treat patients with COVID-19, including Paxlovid, which block the synthesis of virus-related proteins and replication of viral RNA, respectively. Despite satisfactory clinical trial results, attention is now being paid to the long-term side effects of these antiviral drugs on the musculoskeletal system. To date, no study has reported the possible side effects, such as osteoarthritis, of Paxlovid. This study explored the effects of antiviral drug, Paxlovid, on chondrocyte proliferation and differentiation.

Methods: In this study, both in vitro and in vivo studies were performed to determine the effect of Paxlovid on chondrocyte degeneration and senescence. Furthermore, we explored the possible mechanism behind Paxlovid-induced acceleration of cartilage degeneration using transcriptome sequencing and related inhibitors were adopted to verify the downstream pathways behind such phenomenon.

Results: Paxlovid significantly inhibited chondrocyte extracellular matrix protein secretion. Additionally, Paxlovid significantly induced endoplasmic reticulum stress, oxidative stress, and downstream ferroptosis, thus accelerating the senescence and degeneration of chondrocytes. In vivo experiments showed that intraperitoneal injection of Paxlovid for 1 week exacerbated cartilage abrasion and accelerated the development of osteoarthritis in a mouse model.

Conclusions: Paxlovid accelerated cartilage degeneration and osteoarthritis development, potentially by inducing endoplasmic reticulum stress and oxidative stress. Long-term follow-up is needed with special attention to the occurrence and development of osteoarthritis in patients treated with Paxlovid.

Source: Kong K, Chang Y, Qiao H, Zhao C, Chen X, Rong K, Zhang P, Jin M, Zhang J, Li H, Zhai Z. Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis. J Transl Med. 2022 Nov 26;20(1):549. doi: 10.1186/s12967-022-03770-4. PMID: 36435786; PMCID: PMC9701426. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701426/ (Full text)

Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19

Abstract:

Long Covid — the disease encompassing the post-acute sequelae of SARS-CoV-2 (PASC) — affects millions of people around the world. Prevention of PASC is an urgent public health priority. In this work, we aimed to examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of post-acute sequelae.

We used the healthcare databases of the US Department of Veterans Affairs to identify users of the health system who had a SARS-CoV-2 positive test between March 01, 2022 and June 30, 2022, were not hospitalized on the day of the positive test, had at least 1 risk factor for progression to severe COVID-19 illness and survived the first 30 days after SARS-CoV-2 diagnosis. We identify those who were treated with oral nirmatrelvir within 5 days after the positive test (n=9217) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n= 47,123). Inverse probability weighted survival models were used to estimate the effect of nirmatrelvir (versus control) on a prespecified panel of 12 post-acute COVID-19 outcomes and reported as hazard ratio (HR) and absolute risk reduction (ARR) in percentage at 90 days.

Compared to the control group, treatment with nirmatrelvir was associated with reduced risk of PASC (HR 0.74 95% CI (0.69, 0.81), ARR 2.32 (1.73, 2.91)) including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR 0.52 (0.35, 0.77), ARR 0.28 (0.14, 0.41)), and post-acute hospitalization (HR 0.70 (0.61, 0.80), ARR 1.09 (0.72, 1.46)). Nirmatrelvir was associated with reduced risk of PASC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection.

In sum, our results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC regardless of vaccination status and history of prior infection. The totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 reduces the risk of post-acute adverse health outcomes.

Source: Yan Xie, Taeyoung Choi, Ziyad Al-Aly. Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19. medRxiv 2022.11.03.22281783; doi: https://doi.org/10.1101/2022.11.03.22281783 https://www.medrxiv.org/content/10.1101/2022.11.03.22281783v1.full.pdf (Full text)