Oral Molnupiravir and Nirmatrelvir/Ritonavir for the Treatment of COVID-19: A Literature Review with a Focus on Real-World Evidence.

Vaccines remain the cornerstone of medical prevention and are highly effective in reducing the risk of severe disease and death due to coronavirus disease 2019 (COVID-19). In the context of expanding the therapeutic armamentarium against COVID-19, molnupiravir (Lagevrio) and ritonavir-boosted nirmatrelvir (Paxlovid) were developed, constituting the first effective oral treatments against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this narrative review, we retrospectively inquired into the clinical trials and real-world studies investigating the efficacy of these agents. Overall, clinical trials and real-world studies have demonstrated the efficacy of both agents in reducing hospitalization and death rates in COVID-19 patients. As per current recommendations, their use is suggested in patients with mild to moderate symptoms who are at high risk of developing severe disease. Nevertheless, limited data exist regarding their efficacy in specific subpopulations, such as immunocompromised patients, those with severe kidney disease, pregnant women, and children.

Immune Checkpoint Inhibitors and Infection: What Is the Interplay?

Immune checkpoint molecules are receptors expressed on immune cells, especially T-cells, which activate immunosuppressive pathways and lead them to a state known as T-cell exhaustion. Immune checkpoint inhibitors (ICIs) constitute a group of specific antibodies that target these molecules, restoring T-cell effector function. Several ICIs have already been approved by the FDA as therapeutic options for certain malignancies. However, evidence in the literature remains unclear regarding the possible risk of infection in patients receiving this treatment. A thorough examination of existing literature was carried out to investigate whether the use of ICIs increases the likelihood of specific infections and to explore the potential beneficial effects of ICIs on the treatment of infections. Our review found most infectious complications are related to immunosuppressive therapy for immune-related adverse events caused by checkpoint blockade. Current evidence shows that ICIs per se do not seem to generally increase the risk of infection, yet they might increase susceptibility to certain infections, such as tuberculosis. On the other hand, reinvigoration of immune responses triggered by ICIs might play a significant role in pathogen clearance, establishing a possible positive impact of ICIs, especially on chronic infectious diseases, such as HIV infection. Data from preclinical models are limited and larger clinical trials are warranted to shed more light on the effect of immune checkpoint blockade on specific pathogens.

Lomentospora prolificans: An Emerging Opportunistic Fungal Pathogen.

Lomentospora prolificans is an emerging opportunistic pathogen that primarily affects immunocompromised individuals leading to disseminated disease with high mortality rates while also causing infections in healthy populations. Successful recovery from infection is difficult due to high rates of intrinsic resistance to antifungals. Rapid and readily available diagnostic methods, aggressive surgical debridement wherever appropriate, and effective and timely antifungal treatment are the pillars for successful management. Future research will need to clarify the environmental niche of the fungus, further investigate the pathophysiology of infection and define species-specific therapeutic targets.

Mediterranean Spotted Fever: Current Knowledge and Recent Advances.

Mediterranean spotted fever (MSF) is an emerging tick-borne rickettsiosis of the spotted fever group (SFG), endemic in the Mediterranean basin. By virtue of technological innovations in molecular genetics, it has been determined that the causative agent of MSF is Rickettsia conorii subspecies conorii. The arthropod vector of this bacterium is the brown dog tick Rhipicephalus sanguineus. The true nature of the reservoir of R. conorii conorii has not been completely deciphered yet, although many authors theorize that the canine population, other mammals, and the ticks themselves could potentially contribute as reservoirs. Typical symptoms of MSF include fever, maculopapular rash, and a characteristic eschar ("tache noire"). Atypical clinical features and severe multi-organ complications may also be present. All of these manifestations arise from the disseminated infection of the endothelium by R. conorii conorii. Several methods exist for the diagnosis of MSF. Serological tests are widely used and molecular techniques have become increasingly available. Doxycycline remains the treatment of choice, while preventive measures are focused on modification of human behavior and vector control strategies. The purpose of this review is to summarize the current knowledge on the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of MSF.