Proxalutamide for the treatment of COVID‐19 rebound following Paxlovid treatment: Report of four cases and review of the literature

Abstract

Background: The pandemic the coronavirus disease 2019 (COVID-19) has created a global health crisis. Although Paxlovid is recommended for the early-stage treatment of mild-to-moderate COVID-19 in patients at increased risk of progression to severe COVID-19, more and more cases are reported a COVID-19 rebound after Paxlovid treatment. Currently, information on the additional treatment for COVID-19 rebound following Paxlovid treatment is limited.Case Report: Here, we present four cases with COVID-19 who were mild on admission. All cases experienced a COVID-19 rebound and progressed to severe COVID-19, following treatment with Paxlovid (300 mg of nirmatrelvir with 100 mg ritonavir, twice daily for 5 days). After being treated with proxalutamide (300 mg/day), all cases finally turned real-time reverse transcription polymerase chain reaction (RT-PCR) negative. Conclusion:Our cases suggested that proxalutamide might be an effective remedial treatment option for patients experiencing a COVID-19 rebound after Paxlovid treatment.

Leveraging SARS-CoV-2 Main Protease (Mpro) for COVID-19 Mitigation with Selenium-Based Inhibitors

“…Molnupiravir is a prodrug metabolized into an active form, acting as a mutagenic ribonucleoside analog, and inducing mutations in the viral RNA during replication, which can cause errors and prevent the virus from replicating correctly [32]. Other molecules, such as Nirmatrelvir or Bofutrelvir (Figure 1), operate by blocking the main protease (M pro ) of SARS-CoV-2, which is responsible for cutting viral polyproteins into their final functional forms [33,34]. Neither drug is a panacea, as molnupiravir may cause mutations in human DNA, leading regulatory bodies to discourage its use during pregnancy [31].…”

Emerging Landscape of Nanobodies and Their Neutralizing Applications against SARS-CoV-2 Virus

“…Nirmatrelvir (commercialized as Paxlovid, a combination with another HIV protease inhibitor ritonavir), a SARS-CoV-2 main protease (Mpro) inhibitor developed by Pfizer, was approved for treatment of COVID-19. Although it lowers the risk of hospitalization or death by 89% in individuals with mild to moderate COVID-19 and is effective against Omicron, more and more reports suggested that patients experienced a rebound of COVID-19 symptoms after treatment with Paxlovid and progressed to severe COVID-19 . There is currently limited information available on additional treatments for COVID-19 rebound following Paxlovid treatment.…”

“…Although it lowers the risk of hospitalization or death by 89% in individuals with mild to moderate COVID-19 and is effective against Omicron, more and more reports suggested that patients experienced a rebound of COVID-19 symptoms after treatment with Paxlovid and progressed to severe COVID-19. 6 There is currently limited information available on additional treatments for COVID- 19 targeted molecules to fight off infections has a long history that dates back over a century (Figure 1). Due to their great specificity and adaptability, monoclonal antibodies (mAbs) are unquestionably in the vanguard of the fight against COVID-19, even though therapeutic mAbs have been widely used to treat a variety of illnesses, including viral infections, and in molecular imaging, drug discovery, and therapeutics for a variety of diseases, including autoimmune, cardiovascular, and infectious diseases, cancer, as well as inflammation (summarized in Figure 2).…”