Molnupiravir and nirmatrelvir were the first available oral antivirals (OAs) active against SARS-CoV-2. Trials evaluating the efficacy of OAs involved patients unvaccinated and infected with variants different from those currently circulating. We conducted a retrospective study on patients with confirmed SARS-CoV-2 infection treated with OAs during the omicron surge in Italy in order to provide real-life data on the efficacy and safety of OAs during the omicron surge of the COVID-19 pandemic. Among 257 patients, 56.8% received molnupiravir, while 43.2% received nirmatrelvir/ritonavir. Patients in the molnupiravir group were older, had a lower body mass index, and had a higher rate of chronic heart disease than those treated with nirmatrelvir/ritonavir. Three hospitalizations were recorded in the molnupiravir (2.1%) group and one in the nirmatrelvir/ritonavir (0.9%) group. One patient treated with molnupiravir died. The median time to negativity was 8 days in the nirmatrelvir/ritonavir group vs. 10 days in the molnupiravir group, p < 0.01. We recorded 37 ADRs (mainly dysgeusia, diarrhea, and nausea) in 31 individuals (12.1%). Only two patients (0.8%) treated with molnupiravir terminated treatment due to ADRs. In conclusion, in a population of mostly vaccinated patients treated with OAs, we observed a low rate of hospitalization, death, and adverse drug reactions. These rates were lower than those reported in pivotal trials.

In immunocompromised patients, pneumonia presents a diagnostic challenge due to diverse etiologies, nonspecific symptoms, overlapping radiological presentation, frequent co-infections, and the potential for rapid progression to severe disease. Thus, timely and accurate diagnosis of all pathogens is crucial. This narrative review explores the latest advancements in microbiological diagnostic techniques for pneumonia in immunocompromised patients. It covers major available microbiological tools for diagnosing both community-acquired and hospital-acquired pneumonia, encompassing a wide spectrum of pathogens including bacterial, viral, fungal, and parasitic. While traditional culture methods remain pivotal in identifying many pneumonia-causing etiologies, their limitations in sensitivity and time to results have led to the rise of non-invasive antigen tests and molecular diagnostics. These are increasingly employed alongside cultures and microscopy for more efficient diagnosis, mainly in viral and fungal infections. Lastly, we report the future of pneumonia diagnostics, exploring the potential of metagenomics and CRISPR/Cas13a for more precise and rapid pathogen detection in immunocompromised populations.

Background: Among the several therapeutic options assessed for the treatment of coronavirus disease 2019 (COVID-19), tocilizumab (TCZ), an antagonist of the interleukine-6 receptor, has emerged as a promising therapeutic choice, especially for the severe form of the disease. Proper synthesis of the available randomized clinical trials (RCTs) is needed to inform clinical practice. Methods: A systematic review with a meta-analysis of RCTs investigating the efficacy of TCZ in COVID-19 patients was conducted. PubMed, EMBASE, and the Cochrane COVID-19 Study Register were searched up until 30 April 2021. Results: The database search yielded 2885 records; 11 studies were considered eligible for full-text review, and nine met the inclusion criteria. Overall, 3358 patients composed the TCZ arm, and 3131 the comparator group. The main outcome was all-cause mortality at 28–30 days. Subgroup analyses according to trials’ and patients’ features were performed. A trial sequential analysis (TSA) was also carried out to minimize type I and type II errors. According to the fixed-effect model approach, TCZ was associated with a better survival odds ratio (OR) (0.84; 95% confidence interval (CI): 0.75–0.94; I²: 24% (low heterogeneity)). The result was consistent in the subgroup of severe disease (OR: 0.83; 95% CI: 0.74–0.93; I²: 53% (moderate heterogeneity)). However, the TSA illustrated that the required information size was not met unless the study that was the major source of heterogeneity was omitted. Conclusions: TCZ may represent an important weapon against severe COVID-19. Further studies are needed to consolidate this finding.

We conducted a real-life case–control study among outpatients with Omicron SARS-CoV-2 infection to assess the effectiveness of molnupiravir (MNP) in reducing hospital admission, admission to the intensive care unit, and death at day 28. Cases were SARS-CoV-2-positive patients seeking medical care within five days of symptom onset from 1 January to 31 December 2022, who received MNP. Controls were selected from a regional database among positive subjects who did not receive antiviral treatment for SARS-CoV-2. A total of 1382 patients were included (146 cases, 1236 controls). Vaccinated patients had a lower risk of mortality and of the composite outcome (hospital admission, ICU admission, or all-cause death) than unvaccinated ones (0.6% vs. 7.8%, p < 0.001 and 2% vs. 7.8%, p = 0.001, respectively). After full-matching propensity score analysis, MNP-treated subjects had a lower incidence of the composite outcome, although no effect was observed on individual outcomes. In subgroup analyses by vaccination status, MNP was effective in preventing all outcomes among unvaccinated patients and reduced the risk of ICU admission in both vaccinated and unvaccinated patients. Molnupiravir treatment effectively reduced the composite outcome risk in outpatients with SARS-CoV-2 infection, with a more pronounced benefit in unvaccinated patients. These findings highlight MNP’s potential to help prevent disease progression in high-risk patients, thereby supporting its role as an outpatient therapeutic option for COVID-19.

Oritavancin is a novel long-acting lipoglycopeptide with in vitro activity against methicillin-resistant (MR) Gram-positive pathogens and a good bactericidal activity even in presence of biofilm forming bacteria. It has been approved for acute bacterial skin and skin structure infections (ABSSSI), but recent reports have demonstrated possible off-label uses, as for prosthetic joint infections (PJI), which, in more than half of cases, are caused by MR Gram positive organisms. We reported a case of a man in his eighties with a late shoulder PJI caused by methicillin resistant Staphyloccus epidermidis (MRSE) with contraindications for surgical replacement and few oral therapeutic options for a long term suppressive antibiotic therapy. The prosthesis was retained, and the patient received ten outpatient sequential doses of 1200 mg of oritavancin during 28 weeks, based on therapeutic drug monitoring (TDM) as a guide for correct timing of administration of each dose. During oritavancin administration, the patient achieved clinical cure, with disappearance of the pain and regaining pre-infection joint mobility, with no side effects reported and no further surgery or hospitalization needed. The treatment is ongoing as a long-lasting suppressive antimicrobial therapy. Oritavancin could represent an excellent solution for treating PJI caused by MR organism, especially in patients who need a long-term suppressive therapy.