Search Results (46)

Introduction: The emergence of SARS-CoV-2 Omicron subvariants characterized by increased transmissibility and immune escape has raised concerns about the efficacy of current treatments. This systematic review and meta-analysis evaluated pharmacological and non-pharmacological interventions in Omicron-infected non-hospitalized patients, focusing on key clinical outcomes such as hospitalization, respiratory failure, ICU admission, and 30-day mortality. Methods: Searches were performed in MEDLINE, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov (last update: 13 July 2025). Eligible studies reported outcomes on antiviral agents, monoclonal antibodies, adjunctive therapies, or telemedicine. Random-effects meta-analyses were conducted when appropriate, with heterogeneity assessed by I². Publication bias was evaluated via funnel plots and Egger’s test. Subgroup analyses explored sources of heterogeneity. Results: Eighty-eight studies were included. Meta-analyses, comparing treatment vs. no treatment, revealed that nirmatrelvir/ritonavir reduced hospitalization by 52% (RR 0.48, 95% CI 0.36–0.63) and all-cause mortality by 84% (RR 0.16, 95% CI 0.11–0.24). Remdesivir reduced hospitalization by 70% (RR 0.30, 95% CI 0.19–0.47) and respiratory failure by 89% (RR 0.11, 95% CI 0.03–0.44). Sotrovimab decreased hospitalization (RR 0.71, 95% CI 0.54–0.93) and mortality (RR 0.34, 95% CI 0.19–0.61). Molnupiravir modestly reduced hospitalization (RR 0.80, 95% CI 0.70–0.91) and respiratory failure (RR 0.45, 95% CI 0.27–0.77). Conclusions: Nirmatrelvir/ritonavir and remdesivir remain important for reducing severe outcomes, while sotrovimab retains partial efficacy. Rapid access to antivirals remains an important factor in mitigating SARS-CoV-2’s burden. Full article

Remdesivir (RDV) and nirmatrelvir/ritonavir (NMVr) are among the most widely used antivirals in the treatment of COVID-19, aiming to reduce disease severity and progression. Adverse neuropsychiatric effects, such as anxiety, sleep disturbances, and movement disorders, have emerged as significant concerns associated with these treatments. To better understand the safety profiles of RDV and NMVr, this study performs a pharmacovigilance analysis of individual case safety reports (ICSRs) from the EudraVigilance (EV) database. Objectives: This study evaluates the risk of neuropsychiatric adverse events associated with RDV and NMVr. Comparisons with other antiviral drugs, including darunavir, sofosbuvir, ribavirin, tenofovir, ritonavir, and sotrovimab, are also performed to develop a comprehensive understanding of the safety profiles. Methods: A retrospective analysis of ICSRs submitted to EV until 7 July 2024, with data extraction on 12 July 2024, was conducted. Demographic characteristics (age, sex, geographic region, and reporter type) and case severity were included in the descriptive analysis. Disproportionality analysis using reporting odds ratio (ROR) and 95% confidence intervals (CI) was performed to compare adverse drug reaction (ADRs) frequencies across 27 system organ classes (SOCs), with emphasis on “Nervous system disorders” and “Psychiatric disorders. Results: The total number of ICSRs was significantly higher for NMVr (n = 8078) compared to RDV (n = 3934). Nervous system disorders accounted for 3.07% of the total RDV reports and for 17.31% of NMVr reports, while psychiatric disorders represented 0.92% of the total ADRs reported for RDV (n = 60) and 3.61% for NMVr (n = 672). On the other hand, RDV showed a significantly lower frequency of reporting headache compared to NMVr (ROR: 0.1057; 95% CI: 0.0676–0.1653). Conclusions: NMVr presents a higher risk of neuropsychiatric ADRs than RDV, underscoring the need for enhanced monitoring, particularly in patients with preexisting central nervous system (CNS) conditions. These findings contribute to optimizing antiviral safety and informing clinical decision making. Full article

Introduction: High-risk patients with COVID-19 benefit from early treatment to prevent severe outcomes. Sotrovimab, a monoclonal antibody, and oral antivirals such as nirmatrelvir/ritonavir and molnupiravir have been used for early intervention, but their comparative efficacy and safety, particularly during the Omicron-dominant phase, require further evaluation. Methods: A multicenter, retrospective study performed in southern Italy including all adult patients who received early antiviral treatment (sotrovimab or nirmatrelvir/r or molnupiravir) between January 2022 and February 2024 (omicron phase). Demographic, clinical, and treatment-related data were analyzed to assess primary endpoints of 28-day mortality and hospitalization. Logistic regression models identified predictors of key outcomes. Results: A total of 668 high-risk patients treated with sotrovimab (n = 326) or oral antivirals (n = 342: 69 with molnupiravir and 273 with nirmatrelvir/ritonavir) were included. There was no significant difference in 28-day mortality between groups (0.8% sotrovimab vs. 1.8% oral antivirals; p = 0.679). However, patients treated with sotrovimab exhibited a longer median time to SARS-CoV-2 negativization (13 vs. 11 days; p = 0.008) and higher non–COVID-19-related hospitalizations (2.45% vs. 0%; p = 0.003). Multivariable analysis identified cardiovascular or cerebrovascular diseases as the sole significant predictor of prolonged viral positivity (OR 1.585, 95% CI 1.072–2.345; p = 0.021). Additionally, immunocompromised status (OR 16.929, 95% CI 1.835–156.170; p = 0.013) and chronic non-COVID-19 oxygen therapy (OR 10.714, 95% CI 1.623–70.725; p = 0.014) were strongly associated with mortality. Conclusions: Sotrovimab and oral antivirals demonstrated similar efficacy in preventing mortality and hospitalization among high-risk patients. Patient-specific factors, particularly cardiovascular comorbidities and immunosuppression, significantly influenced outcomes and should guide treatment choices. Full article

Despite emerging evidence indicating that molecular SARS-CoV-2 tests performed on saliva have diagnostic sensitivity and specificity comparable to those observed with nasopharyngeal swabs (NPSs), most in vivo follow-up studies on the efficacy of drugs against SARS-CoV-2 have been performed on NPSs, not considering saliva as a possible alternative matrix. For this reason, in this study, we used, in parallel, saliva and NPS samples for the detection of SARS-CoV-2 by real-time RT-PCR in patients receiving Tixagevimab/Cilgavimab, Nirmatrelvir/Ritonavir, or Sotrovimab as a treatment against SARS-CoV-2. Our results showed a good correlation between the NPS and saliva samples for each drug; moreover, comparable changes in the cycle threshold (Ct) levels in saliva and NPSs were observed both 7 days and 30 days after treatment, thus confirming that the saliva represents a good matrix for in vivo follow-up studies verifying the effectiveness of treatments against SARS-CoV-2. Full article

Coronavirus disease-19 (COVID-19) has disproportionately affected certain demographics in England, exacerbating existing health disparities. Effective therapeutics are a critical line of defence against COVID-19, particularly for patients at elevated risk for severe disease. Surveillance systems were established to monitor the usage of COVID-19 therapeutics in hospital and community settings and to inform stewardship. Three antiviral therapies—nirmatrelvir plus ritonavir (Paxlovid^®), remdesivir (Veklury^®), and molnupiravir (Lagevrio^®)—and two neutralising monoclonal antibody therapies (nMAbs)—sotrovimab (Xevudy^®) and casirivimab with imdevimab (Ronapreve^®)—were in use in England between July 2020 and April 2023. This paper aims to illuminate trends in the utilisation of COVID-19 therapeutics treatment in both hospital and community settings, stratified by the Index of Multiple Deprivation (IMD) in England. Chapter 3 of the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) Report 2022 to 2023 also discusses the epidemiological surveillance of these five directly acting antiviral COVID-19 therapeutics’ use in England between 2022 and 2023. Full article

Among the anti-Spike monoclonal antibodies (mAbs), the S-309 derivative sotrovimab was the most successful in having the longest temporal window of clinical use, showing a high degree of resiliency to SARS-CoV-2 evolution interrupted only by the appearance of the BA.2.86* variant of interest (VOI). This success undoubtedly reflects rational selection to target a highly conserved epitope in coronavirus Spike proteins. We review here the efficacy of sotrovimab against different SARS-CoV-2 variants in outpatients and inpatients, discussing both randomized controlled trials and real-world evidence. Although it could not be anticipated at the time of its development and introduction, sotrovimab’s use in immunocompromised individuals who harbor large populations of variant viruses created the conditions for its eventual demise, as antibody selection and viral evolution led to its eventual withdrawal due to inefficacy against later variant lineages. Despite this, based on observational and real-world data, some authorities have continued to promote the use of sotrovimab, but the lack of binding to newer variants strongly argues for the futility of continued use. The story of sotrovimab highlights the power of modern biomedical science to generate novel therapeutics while also providing a cautionary tale for the need to devise strategies to minimize the emergence of resistance to antibody-based therapeutics. Full article

Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection; however, no clinical trial data are available, and combined use of direct-acting antivirals (DAA) and monoclonal antibodies (mAb) has been reported only anecdotally. To assess the cooperative effects of dual drug combinations in vitro, we used a VERO E6 cell-based in vitro system with the ancestral B.1 or the highly divergent BQ.1.1 virus to test pairwise combinations of the licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) and the active metabolite of molnupiravir (EIDD-1931) as well the combination of RDV with four licensed mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested only with the susceptible B.1 virus). According to SynergyFinder 3.0 summary and weighted scores, all the combinations had an additive effect. Within DAA/DAA combinations, paired scores with the B.1 and BQ.1.1 variants were comparable. In the post hoc analysis weighting synergy by concentrations, several cases of highly synergistic scores were detected at specific drug concentrations, both for DAA/DAA and for RDV/mAb combinations. This was supported by in vitro confirmation experiments showing a more than a linear shift of a drug-effective concentration (IC₅₀) at increasing concentrations of the companion drug, although the effect was prominent with DAA/DAA combinations and minimal or null with RDV/mAb combinations. These results support the cooperative effects of dual drug combinations in vitro, which should be further investigated in animal models before introduction into the clinic. Full article

The spread of COVID-19 continues, expressed by periodic wave-like increases in morbidity and mortality. The reason for the periodic increases in morbidity is the emergence and spread of novel genetic variants of SARS-CoV-2. A decrease in the efficacy of monoclonal antibodies (mAbs) has been reported, especially against Omicron subvariants. There have been reports of a decrease in the efficacy of specific antiviral drugs as a result of mutations in the genes of non-structural proteins. This indicates the urgent need for practical healthcare to constantly monitor pathogen variability and its effect on the efficacy of preventive and therapeutic drugs. As part of this study, we report the results of the continuous monitoring of COVID-19 in Moscow using genetic and virological methods. As a result of this monitoring, we determined the dominant genetic variants and identified the variants that are most widespread, not only in Moscow, but also in other countries. A collection of viruses from more than 500 SARS-CoV-2 isolates has been obtained and characterized. The genetic lines XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, representing the greatest concern, were identified among the dominant variants. We studied the in vitro efficacy of mAbs Tixagevimab + Cilgavimab (Evusheld), Sotrovimab, Regdanvimab, Casirivimab + Imdevimab (Ronapreve), and Bebtelovimab, as well as the specific antiviral drugs Remdesivir, Molnupiravir, and Nirmatrelvir, against these genetic lines. At the current stage of the COVID-19 pandemic, the use of mAbs developed against early SARS-CoV-2 variants has little prospect. Specific antiviral drugs retain their activity, but further monitoring is needed to assess the risk of their efficacy being reduced and adjust recommendations for their use. Full article

Prolonged SARS-CoV-2 infections are widely described in immunosuppressed patients, but safe and effective treatment strategies are lacking. We aimed to outline our approach to treating persistent COVID-19 in patients with immunosuppression from different causes. In this case series, we retrospectively enrolled all immunosuppressed patients with persistent SARS-CoV-2 infections treated at our centers between March 2022 and February 2023. Patients received different sequential or combination regimens, including antivirals (remdesivir, nirmatrelvir/ritonavir, or molnupiravir) and/or monoclonal antibodies (mAbs) (tixagevimab/cilgavimab or sotrovimab). The main outcome was a complete virological response (negative SARS-CoV-2 RT-PCR on nasopharyngeal swabs) at the end of treatment. Fifteen patients were included as follows: eleven (11/15; 73%) with hematological disease and four (4/15; 27%) with recently diagnosed HIV/AIDS infection. Six patients (6/15; 40%) received a single antiviral course, four patients (4/15; 27%) received an antiviral and mAbs sequentially, and two patients (13%) received three lines of treatment (a sequence of three antivirals or two antivirals and mAbs). A combination of two antivirals or one antiviral plus mAbs was administered in three cases (3/15, 20%). One patient died while still positive for SARS-CoV-2, while fourteen (14/15; 93%) tested negative within 16 days after the end of treatment. The median time to negativization since the last treatment was 2.5 days. Both sequential and combination regimens used in this study demonstrated high efficacy and safety in the high-risk group of immunosuppressed patients. Full article

(1) Introduction: Since May 2021, sotrovimab has been available in Italy for early treatment of SARS-CoV-2 infection and to prevent disease progression. However, some in vitro studies have questioned its efficacy on Omicron variants. Therefore, we aim to further investigate the efficacy of sotrovimab in real-life settings. (2) Methods: We conducted a retrospective study collecting medical records of people with SARS-CoV-2 infection evaluated in the infectious diseases units of Sassari, Foggia, and Bari, Italy. We included people with SARS-CoV-2 infection treated with sotrovimab and people who did not receive any treatment in 2022. The primary study outcome was to evaluate the efficacy of sotrovimab in reducing disease progression (defined as the necessity of starting oxygen supplementation) and COVID-19-related death. The secondary outcome was to evaluate the safety of sotrovimab. (3) Results: We included 689 people; of them, 341 were treated with sotrovimab, while 348 did not receive any treatment. Overall, we registered 161 (23.4%) disease progressions and 65 (9.4%) deaths, with a significant difference between treated and not-treated people (p < 0.001). In the multivariate logistic regression, increasing age [OR for ten years increasing age 1.23 (95%CI 1.04–1.45)] was associated with a higher risk of disease progression. In addition, cardiovascular disease [OR 1.69 (1.01–2.80), fever [OR 3.88 (95%CI 2.35–6.38)], and dyspnea [OR 7.24 (95%CI 4.17–12.58)] were associated with an increased risk of disease progression. In contrast, vaccination [OR 0.21 (95%CI 0.12–0.37)] and sotrovimab administration [OR 0.05 (95%CI 0.02–0.11)] were associated with a lower risk of developing severe COVID-19. Regarding mortality, people with older age [OR for ten years increasing age 1.36 (95%CI 1.09–1.69)] had a higher risk of death. In addition, in the multivariate analysis, cardiovascular disease lost statistical significance, while people on chemotherapy for haematological cancer [OR 4.07 (95%CI 1.45–11.4)] and those with dyspnea at diagnosis [OR 3.63 (95%CI 2.02–6.50)] had an increased risk of death. In contrast, vaccination [OR 0.37 (95%CI 0.20–0.68)] and sotrovimab treatment [OR 0.16 (95%CI 0.06–0.42)] were associated with lower risk. Only two adverse events were reported; one person complained of diarrhoea a few hours after sotrovimab administration, and one had an allergic reaction with cutaneous rash and itching. (4) Conclusions: Our study showed that sotrovimab treatment was associated with a reduction of the risk of disease progression and death in SARS-CoV-2-infected people, 70% of whom were over 65 years and a with high vaccination rate, with excellent safety. Therefore, our results reinforce the evidence about the efficacy and safety of sotrovimab during the Omicron era in a real-world setting. Full article

Background: Monoclonal antibodies are designed to target specific proteins of COVID-19 and can be used as a treatment for people with mild to moderate infection and at a high risk of severe disease. Casirivimab/imdevimab, sotrovimab, and Bamlanivimab/etesevimab have been authorized for emergency use in the treatment of COVID-19. However, during pregnancy, these drugs have not been extensively studied. Methods: A total of 22 pregnant women with mild to moderate infection were treated with three different monoclonal antibodies, and efficacy and safety were evaluated in the first period and until six months of follow-up. Results: No infusion/allergic reactions occurred. No fatal or adverse events were observed in the pregnant women or fetus. The time of negativization with sotrovimab was shorter in comparison to Imdevimav/casirivimab (p = 0.0187) and Bamlanivimab/etesevimab (p < 0.00001). The time of negativization with sotrovimab was earlier in comparison to Imdevimav/casirivimab (t-value: 2.92; p = 0.0052) in vaccinated patients and similar in comparison to Imdevimav/casirivimab (t-value: 1.48; p = 0.08). In unvaccinated patients, sotrovimab was faster to achieve negativization in comparison to Bamlanivimab/etesevimab (t-value: 10.75; p < 0.0005). Conclusions: Pregnant COVID-19 patients receiving sotrovimab obtained better clinical outcomes. Pregnancy or neonatal complications were not observed after monoclonal treatment, confirming the safety and tolerability of these drugs in pregnant women. Full article

Background Sotrovimab, a monoclonal antibody against SARS-CoV-2, is used as a pre-exposition prophylaxis (PrEP) against COVID-19, but monitoring strategies using routine test systems have not been defined. Methods Twenty kidney transplant recipients without antibodies after vaccination received 500 mg Sotrovimab. Antibody levels were quantified over eight weeks using live-virus neutralization (BA1 and BA2), antibody binding assays (TrimericS, Elecsys, QuantiVAC) and surrogate virus neutralization tests (sVNTs; TECOmedical, cPass and NeutraLISA). Results Sotrovimab neutralized both Omicron subvariants (BA1 NT titer 90 (+−50) > BA2 NT titer 33 (+−15) one hour post infusion). Sotrovimab was measurable on all used immunoassays, although a prior 1:100 dilution was necessary for Elecsys due to a presumed prozone effect. The best correlation with live-virus neutralization titers was found for QuantiVAC and TrimericS, with a respective R² of 0.65/0.59 and 0.76/0.57 against BA1/BA2. Elecsys showed an R² of 0.56/0.54 for BA1/BA2, respectively. sVNT values increased after infusion but had only a poor correlation with live-virus neutralization titers (TECOmedical and cPass) or did not reach positivity thresholds (NeutraLISA). Conclusion Antibody measurements by the used immunoassays showed differences in antibody levels and only a limited correlation with neutralization capacity. We do not recommend sVNTs for monitoring SARS-CoV-2 neutralization by Sotrovimab. Full article

Sotrovimab, an antibody active against severe acute respiratory syndrome coronavirus 2 that neutralizes antibodies, reduced the risk of COVID-19-related hospitalization or death in studies conducted before the emergence of the Omicron variant. The objective of this study is to evaluate the clinical efficacy of sotrovimab in patients with mild to moderate COVID-19 Omicron BA.1 and BA.2 subvariant infections using a propensity score matching method. The propensity score-matched cohort study population was derived from patients who received sotrovimab. We derived a comparator group from an age- and sex-matched population who were recuperating in a medical facility after COVID-19 infection or from elderly person entrance facilities during the same period who were eligible for but did not receive sotrovimab treatment. In total, 642 patients in the BA.1 subvariant group and 202 in the BA.2 subvariant group and matched individuals were analyzed. The outcome was the requirement for oxygen therapy. In the treatment group, 26 patients with the BA.1 subvariant and 8 patients with the BA.2 subvariant received oxygen therapy. The administration of oxygen therapy was significantly lower in the treatment group than in the control group (BA.1 subvariant group, 4.0% vs. 8.7%, p = 0.0008; BA.2 subvariant group, 4.0% vs. 9.9%, p = 0.0296). All these patients were admitted to our hospitals and received additional therapy and then recovered. No deaths were observed in either group. Our results demonstrate that the sotrovimab antibody treatment may be associated with a reduction in the requirement for oxygen therapy among high-risk patients with mild to moderate COVID-19 Omicron BA.1 and BA.2 subvariants. Full article

Objectives: Monoclonal antibodies (mAbs) have proven to be a valuable tool against COVID-19, mostly among subjects with risk factors for progression to severe illness. Tixagevimab/cilgavimab (TIX/CIL), a combination of two Fc-modified human monoclonal antibodies, has been recently approved to be employed as early treatment. Methods: Two groups of immunocompromised patients exposed to different early treatments (i.e., TIX/CIL vs. other mAbs [casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab]) were compared in terms of clinical outcomes (hospitalisation and mortality within 14 days from administration) and time to the negativity of nasal swabs. We used either Pearson’s chi-square or Fisher’s exact test for categorical variables, whereas the Wilcoxon rank–sum test was employed for continuous ones. Kaplan–Meier curves were produced to compare the time to nasopharyngeal swab negativity. Results: Early treatment with TIX/CIL was administered to 19 immunocompromised patients, while 89 patients received other mAbs. Most of them were solid organ transplant recipients or suffering from hematologic or solid malignancies. Overall, no significant difference was observed between the two groups regarding clinical outcomes. In the TIX/CIL group, one patient (1/19, 5.3%), who was admitted to the emergency room within the first 14 days from treatment and was hospitalised due to COVID-19 progression, died. Regarding the time to nasal swab negativity, no significant difference (p = 0.088) emerged. Conclusions: Early treatment of SARS-CoV-2 infection with TIX/CIL showed favourable outcomes in a small group of immunocompromised patients, reporting no significant difference compared to similar patients treated with other mAbs. Full article

Since the COVID-19 outbreak began, an association between COVID-19 and thrombotic diseases has been underlined. Although this association is more frequent with venous thromboembolism, ischaemic stroke has also been reported as a thrombotic complication in several cohorts of affected patients. Furthermore, the association between ischaemic stroke and COVID-19 has been considered a risk factor for early mortality. On the other hand, after the successful vaccination campaign, the incidence and the virulence of SARS-CoV-2 decreased, though it has been observed that COVID-19 may induce a severe infection in specific cohorts of frail subjects. For this reason, different drugs have been introduced of an antiviral action in order to improve the disease outcome of frail patients. In this field, with the arrival of a neutralizing monoclonal antibody against SARS-CoV-2, in particular, sotrovimab, a further chance to treat high-risk patients with mild-to-moderate COVID-19 arrived, achieving a concrete reduction in the risk of disease progression. We here report our clinical experience of an ischaemic stroke occurring a few minutes after the administration of sotrovimab for the treatment of moderate COVID-19 in a frail patient with chronic lymphocytic leukaemia. Other causes of ischaemic stroke were ruled out, and in order to evaluate the probability of a rare side effect, the Naranjo probability scale has also been utilized. In conclusion, among several side effects that have been described during the treatment of COVID-19 with sotrovimab, ischaemic stroke was not reported. Therefore, we here report a rare case of ischaemic stroke with early clinical manifestation after the administration of sotrovimab for the treatment of moderate COVID-19 in an immunocompromised patient for the first time. Full article