First-generation oral antivirals against SARS-CoV-2.

BACKGROUND: Oral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization for the treatment of mild-to-moderate COVID-19 in non-hospitalized patients who are at high risk for clinical progression. OBJECTIVES: To provide a clinical practice overview of first-generation oral antiviral agents against SARS-CoV-2. SOURCES: References for this review were identified through searches of PubMed, Google Scholar, bioRxiv, medRxiv, regulatory drug agencies, and pharmaceutical companies' websites up to 16 February 2022. CONTENT: Molnupiravir and nirmatrelvir and ritonavir have been authorized for use in nonhospitalized individuals with mild-to-moderate COVID-19 who are at high risk for progression. In clinical trials, molnupiravir reduced the frequency of hospitalization or death by 3% (relative risk reduction 30%), and nirmatrelvir and ritonavir by 6% (relative risk reduction 89%). Their use in clinical practice requires early administration, review of drug-drug interactions (nirmatrelvir and ritonavir), considerations of embryo-fetal toxicity (molnupiravir), and compliance with ingestion of a high number of pills. Knowledge gaps include the efficacy of these agents in vaccinated, hospitalized, or immunosuppressed individuals with prolonged SARS-CoV-2 persistence. IMPLICATIONS: First-generation oral antivirals represent progress in therapeutics against SARS-CoV-2, but also pose new challenges in clinical practice. Further advances in the development of new drugs are required.

CD4+ T-cell help enhances NK cell function following therapeutic HIV-1 vaccination.

UNLABELLED: Increasing data suggest that NK cells can mediate antiviral activity in HIV-1-infected humans, and as such, novel approaches harnessing the anti-HIV-1 function of both T cells and NK cells represent attractive options to improve future HIV-1 immunotherapies. Chronic progressive HIV-1 infection has been associated with a loss of CD4(+) T helper cell function and with the accumulation of anergic NK cells. As several studies have suggested that cytokines produced by CD4(+) T cells are required to enhance NK cell function in various infection models, we hypothesized that reconstitution of HIV-1-specific CD4(+) T-cell responses by therapeutic immunization would restore NK cell activity in infected individuals. Using flow cytometry, we examined the function of CD4(+) T cells and NK cells in response to HIV-1 in subjects with treated chronic HIV-1 infection before and after immunization with an adjuvanted HIV-1 Gp120/NefTat subunit protein vaccine candidate provided by GlaxoSmithKline. Vaccination induced an increased expression of interleukin-2 (IL-2) by Gp120-specific CD4(+) T cells in response to HIV-1 peptides ex vivo, which was associated with enhanced production of gamma interferon (IFN-γ) by NK cells. Our data show that reconstitution of HIV-1-specific CD4(+) T-cell function by therapeutic immunization can enhance NK cell activity in HIV-1-infected individuals. IMPORTANCE: NK cells are effector cells of the innate immune system and are important in the control of viral infection. Recent studies have demonstrated the crucial role played by NK cells in controlling and/or limiting acquisition of HIV-1 infection. However, NK cell function is impaired during progressive HIV-1 infection. We recently showed that therapeutic immunization of treated HIV-1-infected individuals reconstituted strong T-cell responses, measured notably by their production of IL-2, a cytokine that can activate NK cells. The current study suggests that reconstitution of T-cell function by therapeutic vaccination can enhance NK cell activity in individuals with chronic HIV-1 infection. Our findings provide new insights into the interplay between adaptive and innate immune mechanisms involved in HIV-1 immunity and unveil opportunities to harness NK cell function in future therapeutic vaccine strategies to target HIV-1.

A Case of Septic Arthritis of the Shoulder Due to Yersinia enterocolitica with Review of the Literature.

Yersinia enterocolitica infection rarely can cause extra-intestinal infections. We present a case of septic arthritis of the shoulder due to this organism in an elderly man with liver and cardiac disease. We review previously published cases of Y. enterocolitica septic arthritis, and discuss risk factors and management.