Paxlovid (nirmatrelvir/ritonavir) / Pfizer, China Meheco Group - LARVOL DELTA

Patient Experiences With Nirmatrelvir/Ritonavir for COVID-19 in a Collaborative Care Model: A Cross-Sectional Study on Self-Management, Information, and Medication Impact. (PubMed, J Patient Exp) - "Patient management of nirmatrelvir/r and cotreatments was successful, but satisfaction toward nirmatrelvir/r information could be improved. This study highlights the importance of ongoing efforts to ensure communication strategies, patient education, and interprofessional collaboration in providing treatments with drug-drug interactions."

Journal • Observational data • Infectious Disease • Novel Coronavirus Disease

A novel, covalent broad-spectrum inhibitor targeting human coronavirus Mpro. (PubMed, Nat Commun) - "Furthermore, ISM3312 shows significant inhibitory effects against Nirmatrelvir-resistant Mpro mutants, suggesting ISM3312 may contribute to reduced viral escape in these settings. Incorporating ISM3312 and Nirmatrelvir into antiviral strategy could improve preparedness and reinforce defenses against future coronavirus threats."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Case Report: Persistent COVID-19 in a fully vaccinated Japanese man being treated with rituximab and epcoritamab for diffuse large B-cell lymphoma. (PubMed, Front Med (Lausanne)) - "The patient was treated with a combination of remdesivir, sotrovimab, and nirmatrelvir/ritonavir, and recovered clinically. This case highlights the challenges associated with managing persistent SARS-CoV-2 infection in immunocompromised patients with hematological malignancies. Combined treatment with antivirals and monoclonal antibodies may be an effective strategy."

Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Natural and Designed Cyclic Peptides as Potential Antiviral Drugs to Combat Future Coronavirus Outbreaks. (PubMed, Molecules) - "Additionally, the high costs of current treatments such as Remdesivir and Paxlovid highlight the need for more affordable antiviral drugs. This review emphasizes the urgent need to develop specific and broad-spectrum antiviral drugs and highlights cyclic peptides as a sustainable solution to combat future pandemics. Further research into these compounds could provide a new weapon to combat RNA viruses and address the gaps in current antiviral drug development."

Journal • Review • Ebola Virus Disease • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A retrospective cohort study of the efficacy and safety of oral azvudine versus nirmatrelvir/ritonavir in elderly hospitalized COVID-19 patients aged over 60 years. (PubMed, Acta Pharm Sin B) - "Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients."

Clinical • Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Oncology • Solid Tumor

Effectiveness and safety of azvudine versus nirmatrelvir/ritonavir in hospitalized patients with COVID-19. (PubMed, BMC Infect Dis) - "In hospitalized patients with COVID-19, the effectiveness of azvudine and nirmatrelvir/ritonavir was found to be comparable in various aspects, including the improved discharge rate, the improvement time, time to fever resolution, usage rates of high-flow nasal cannula, non-invasive mechanical ventilation, and invasive mechanical ventilation, rate of disease progression, time to discharge, and hospital length of stay. The occurrence of myocardial injury was higher in nirmatrelvir/ritonavir group compared to azvudine group, while no significant differences were observed in other adverse reactions."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Identification, validation, and characterization of approved and investigational drugs interfering with the SARS-CoV-2 endoribonuclease Nsp15. (PubMed, Protein Sci) - "Despite the rapid development of antiviral vaccines and some approved treatments such as remdesivir and paxlovid, effective antiviral pharmacological treatments for COVID-19 patients remain limited. Additionally, the study emphasizes the potential of combination therapies targeting multiple viral processes to enhance treatment efficacy and reduce the risk of drug resistance. This research contributes to the ongoing efforts to develop effective antiviral therapies for SARS-CoV-2 and possibly other coronaviruses."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Not Every Pleural Effusion Is an Empyema: A Case of Rheumatoid Arthritis Pleurisy (ATS 2025) - "She has a pertinent past medical history of rheumatoid arthritis which was recently changed to infliximab about six months prior...She tested positive for COVID-19 four days prior to her ED visit and due to her immune status, she was started on Paxlovid therapy. She never required supplemental oxygen and was not treated with steroids or rituximab...A broad differential diagnosis is essential when treating a pleural effusion. Not all exudative effusions are parapneumonic effusions, particularly in patients with rheumatological manifestations; this differential is necessary in order to appropriate manage patients."

Clinical • Pleural effusion • Asthma • Cardiovascular • Endocrine Disorders • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Arthritis • Novel Coronavirus Disease • Pulmonary Embolism • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

CanTreatCOVID: Canadian Adaptive Platform Trial of Treatments for COVID-19 in Community Settings (clinicaltrials.gov) - P3 | N=797 | Active, not recruiting | Sponsor: Unity Health Toronto | Recruiting ➔ Active, not recruiting | N=10000 ➔ 797 | Trial completion date: Mar 2026 ➔ Jun 2025 | Trial primary completion date: Mar 2026 ➔ Apr 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Comparative Analysis of Early COVID-19 Treatment Efficacy in a Multicentric Regional Cohort in Italy: Emulation of a Series of Target Trials. (PubMed, J Med Virol) - "Participants received either nirmatrelvir/ritonavir (NMV/r), molnupiravir (MLP), remdesivir (RDV), sotrovimab (SOT), or tixagevimab/cilgavimab (TIX/CIL). Weighted analysis showed that NMV/r and MLP were superior to all other interventions. In our population of individuals at high risk of progression to severe disease, there was clinical benefit in using NMV/r or MLP instead of mAbs-based therapies or RDV."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease

The financial value of improving patient access to COVID-19 antiviral therapy in Medicare Part D: A simulation study. (PubMed, J Manag Care Spec Pharm) - "Individual Medicare plans should consider the overall clinical and cost impacts of nirmatrelvir-ritonavir on the health system when determining formulary tier placement. Better alignment of incentives for PDPs is needed to address the financial barriers to expanding access for therapies that can improve clinical outcomes and produce savings to the Medicare program."

Journal • Medicare • Reimbursement • US reimbursement • Infectious Disease • Novel Coronavirus Disease

Antiviral prescription of mild to moderate COVID-19 and adherence to official recommendations in Spanish emergency departments. (PubMed, Emergencias) - "The incidence of missed opportunities to prescribe antiviral therapy is high. Incidences vary across hospitals and more often involve the most vulnerable patients."

Journal • Retrospective data • Genetic Disorders • Infectious Disease • Novel Coronavirus Disease • Obesity

A Study to Learn About the Study Medicine (Nirmatrelvir Plus Ritonavir) in Pregnant Women With COVID-19 (clinicaltrials.gov) - P1 | N=25 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=49 ➔ 25 | Trial completion date: Aug 2025 ➔ May 2025

Enrollment change • Enrollment closed • Trial completion date • Infectious Disease • Novel Coronavirus Disease

Clinical Characteristics and Treatment Efficacy in Patients With SARS-CoV-2 Positivity After Nirmatrelvir-Ritonavir Therapy. (PubMed, J Med Virol) - "SARS-CoV-2 positivity after NMV-r treatment is common and associated with worse clinical outcomes. Extending NMV-r therapy may reduce disease progression risk; this finding requires confirmation in future studies."

Journal • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

ILD or Covid: A Case of Chameleons (ATS 2025) - "Her medications included tylenol and naproxen-esomeprazole...While her respiratory symptoms and pulmonary opacities improved, in March she received rituximab for RA flare...She received 10 days of remdesivir, a dose of intravenous immunoglobulin G, and continued on prednisone 10 mg with rapid resolution of symptoms and improvement of radiographic findings. Ten days of nirmatrelvir with ritonavir were given to facilitate complete Covid clearance...DISCUSSION Pulmonary manifestations of RA can include organizing pneumonia, interstitial lung disease, bronchiectasis, pulmonary arterial hypertension, pleural effusion, and increased risk of infection due to immunosuppression. While Covid can also cause organizing pneumonia and pulmonary fibrosis, our case highlights how prolonged Covid infection without classic symptoms or hypoxia can mimic ILD."

Clinical • Anemia • Aplastic Anemia • Back Pain • Bronchiectasis • Cardiovascular • Cough • Hematological Disorders • Hematological Malignancies • Immunology • Interstitial Lung Disease • Musculoskeletal Pain • Myelodysplastic Syndrome • Novel Coronavirus Disease • Oncology • Pain • Pneumonia • Pulmonary Arterial Hypertension • Rheumatology • Vasculitis • CRP

Acute Hypersensitivity Pneumonitis as a Sequela of COVID-19 Pneumonia (ATS 2025) - "The patient was diagnosed with COVID-19 pneumonia at the time of her symptom onset and treated with nirmatrelvir-ritonavir...ConclusionKnowledge about association between COVID-19 infection and acute HP is essential to avoid unnecessary work up and to avoid delay in the establishment of diagnosis. Early recognition and initiation of steroids is the key to successful therapy as delay in treatment can lead to ongoing inflammation causing irreversible fibrosis."

Cough • Fibrosis • Immunology • Infectious Disease • Inflammation • Interstitial Lung Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Rheumatology • CD4 • CD8

Proinflammatory Pulmonary Effects of SARS-CoV-2 Main Protease in Mice and Human Bronchial Epithelial Cells (ATS 2025) - "Cells exposed to heat-inactivated Mpro or Mpro inhibited by nirmatrelvir showed a diminished but not abolished response, which may suggest the participation of other pathways besides the protease activity alone... The presence of free Mpro in COVID-19 patients' lungs may trigger an inflammatory response that might exacerbate pulmonary damage and contribute to respiratory symptoms. Our findings demonstrate that the administration of Mpro protein by itself, without the presence of SARS-CoV-2 virus, is capable to induce an inflammatory response in mouse lungs and in human bronchial epithelial cells, and that this response is ameliorated, but not abolished, by Mpro heat-inactivation or inhibition. This suggests that Mpro activates additional pro-inflammatory pathways independent from its proteolytic activity."

Preclinical • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • SPECC1

Clinical Features of Patients With COVID-19 Recurrence During Hospitalization in the Omicron Variant Surge (ATS 2025) - "Of the 7 patients, 6 (85.7%) were initially treated with remdesivir (RDV), but only 3 patients were re-treated with RDV, and the other 4 patients were successfully re-treated with oral 3C-like protease inhibitors, such as ensitrelvir (ESV) and nirmatrelvir/ritonavir (N/R). These data suggest that COVID-19 recurrence was found in patients with hematological disorders, such as lymphoma, and/or patients with no vaccination history. However, these patients were treated successfully by re-administration of anti-SARS-CoV-2 agents, including ESV and N/R."

Clinical • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases

SNS812, a Broad-Spectrum Antiviral siRNA, Demonstrates Safety and Clinical Efficacy in Treating COVID-19 in Phase I and II Trial (ATS 2025) - P1, P2 | "Mainstream treatments, like protease inhibitors and nucleoside analogs, have shown limited efficacy, particularly in vaccinated individuals, and are associated with a high rate of drug-related side effects, as demonstrated in recent Paxlovid trials. SNS812 demonstrated an excellent safety profile in both Phase I and II trials, showing significant clinical efficacy in symptom resolution and viral clearance. Its effectiveness against immune-evasive variants in vaccinated participants suggests that SNS812 could be a promising broad-spectrum antiviral therapy for COVID-19."

Clinical • P1 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Paxlovid-Induced SIADH (ATS 2025) - "Case: A 75-year-old female with a history of hypothyroidism and hypertension, managed with hydrochlorothiazide (HCTZ) for several years, presented to the emergency department with mild abdominal pain, nausea, vomiting, and generalized malaise for two days. This case illustrates a rare instance of Paxlovid induced SIADH, emphasizing the importance of recognizing potential adverse effects in COVID-19 treatment. Clinician awareness is crucial, as prompt discontinuation and supportive care can help prevent the risk of severe hyponatremia."

Cardiovascular • CNS Disorders • Endocrine Disorders • Epilepsy • Heart Failure • Hypertension • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pain • Pneumonia • Pulmonary Disease • Respiratory Diseases

Toxic as FK - A Case of Paxlovid-Induced Tacrolimus (FK506) Toxicity in a Kidney Transplant Recipient with COVID-19 (ATS 2025) - "She was diagnosed with sepsis secondary to COVID-19 and treated with intravenous fluids, broad-spectrum antibiotics, and remdesivir...Given that tacrolimus is not dialyzable, the critical care pharmacist and transplant nephrology team recommended initiating rifampin and phenytoin to enhance tacrolimus metabolism...Frequent monitoring of tacrolimus levels and timely recognition of toxicity are crucial to mitigate risks in this vulnerable population. Given the increasing use of CYP3A4 inhibitors like ritonavir, clinicians must remain vigilant and adjust treatment strategies to prevent potentially harmful drug interactions and toxicity."

Clinical • Cardiovascular • CNS Disorders • Epilepsy • Fatigue • Infectious Disease • Metabolic Disorders • Movement Disorders • Nephrology • Novel Coronavirus Disease • Pain • Renal Disease • Septic Shock • Solid Organ Transplantation • Transplantation

Efficacy and safety of antiviral treatments for symptomatic COVID-19 outpatients: network meta-analysis and budget impact analysis. (PubMed, Front Pharmacol) - "Remdesivir (RDV) and nirmatrelvir/ritonavir (NRM/RTV) are two antiviral agents for treating outpatient adults with mild to moderate symptomatic COVID-19 at high risk of developing a severe disease. The comparison of the two antiviral therapies for the early treatment of COVID-19 did not yield statistically significant differences in the potential efficacy and safety to prevent hospitalisation or serious adverse events. However, the results of the cost-analysis showed a saving in favour of NRM/RTV."

HEOR • Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease

Impact of Administrative Problems on Severe Adverse Event Outcomes for COVID-19 Antiviral Medications (ISPOR 2025) - "OBJECTIVES: The U.S. FDA approved nirmatrelvir/ritonavir, remdesivir, and molnupiravir to address the COVID-19 pandemic. Remdesivir was significantly more likely to be associated with severe AE outcomes following administrative problems. Enhanced pharmacovigilance systems are needed to identify and address administrative challenges early, ensuring safer and more effective use of COVID-19 antiviral therapies."

Adverse events • Infectious Disease • Novel Coronavirus Disease

Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MPro inhibitors with potent in vivo efficacy. (PubMed, Sci Adv) - "AVI-4516 also exhibits synergy with the RNA-dependent RNA polymerase inhibitor, molnupiravir, in cellular infection models. Related analogs strongly inhibit nirmatrelvir-resistant MPro mutant virus. The properties of this chemotype are differentiated from existing clinical and preclinical MPro inhibitors and will advance therapeutic development against emerging SARS-CoV-2 variants and other coronaviruses."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety and Effectiveness of Nirmatrelvir-Ritonavir in Patients With Advanced Kidney Dysfunction and COVID-19. (PubMed, Am J Kidney Dis) - "Nirmatrelvir-ritonavir use in the setting of advanced kidney dysfunction was associated with a reduced risk of acute respiratory failure and pneumonia, and no detectable differences in non-respiratory adverse outcomes compared with no treatment with either nirmatrelvir-ritonavir or molnupiravir."

Journal • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Hepatology • Hypertension • Infectious Disease • Liver Failure • Nephrology • Novel Coronavirus Disease • Pneumonia • Renal Disease • Respiratory Diseases