Search Results (61)

Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article

Background/Objectives: Despite significant advancements in vaccine development and distribution, the optimal timing and integration of COVID-19 vaccination in Canada remain crucial to public health. As the SARS-CoV-2 virus continues to evolve, determining effective timing strategies for booster doses is necessary to sustain immunity, especially in high-risk populations. This systematic review aims to critically evaluate the timing and co-administration strategies of COVID-19 vaccines in Canada, comparing them with approaches in other G7 nations. Methods: The review seeks to identify best practices to inform national vaccination policies, with a particular focus on synchronizing COVID-19 and seasonal influenza vaccinations. We systematically searched Scopus, PubMed, Medline, and Web of Science (17 August 2021 to 7 July 2024) using the PECOS framework. Two independent reviewers screened titles/abstracts, extracted key data on immunogenicity, efficacy, and safety, and performed a narrative synthesis on timing and co-administration outcomes. Results: Evidence summarized across G7 countries reveals that most nations are converging on annual or flexible booster schedules tailored to high-risk groups, often aligning COVID-19 vaccination with influenza campaigns. Countries like Canada, the UK, and the US have integrated these efforts, while others maintain more independent or heterogeneous approaches. In addition, timely booster doses, whether administered annually or more frequently in high-risk settings, consistently reduce infection rates and hospitalizations. Conclusions: These findings collectively support the continued evolution of COVID-19 vaccination programs toward integrated, seasonally aligned strategies. Future public health efforts can build on these lessons not only to sustain protection against SARS-CoV-2 but also to strengthen preparedness for other respiratory infections. Full article

Introduction: Highly pathogenic avian influenza (HPAI) H5N1, a zoonotic virus primarily affecting birds, has shown increasing cross-species transmission, including to domestic animals such as cats. Recent reports of cat infections, often associated with contact with infected birds or the consumption of raw milk from H5N1-positive cattle, raise concerns about their role in viral adaptation and zoonotic transmission. Objective: To assess the global prevalence and characteristics of H5N1 infections in cats (Felis catus) through a systematic review and meta-analysis. Methods: Following PRISMA guidelines, we conducted a systematic search across PubMed, Scopus, and Web of Science up to 1 March 2025. Observational studies reporting the prevalence or seroprevalence of H5N1 in cats (Felis catus) were included. Data extraction and quality assessment were performed independently by four reviewers. Meta-analyses were conducted using a random-effects model, and heterogeneity was assessed via I² statistics. Results: Twenty-one studies met the inclusion criteria, of which eight were included in the meta-analysis (n = 3586 cats). The pooled global prevalence of Felis catus infections due to H5N1 influenza was 0.7% (95%CI: 0.3–1.1%), with high heterogeneity (I² = 86.5%). The prevalence varied by the diagnostic method, region, cat type, and time. Domestic cats and those in Africa had higher infection rates (20.0% and 32.0%, respectively). Case reports (n = 35) revealed a high mortality (74%), predominantly from clade 2.3.4.4b, with neurological and respiratory manifestations. Conclusions: Although the overall prevalence is low, H5N1 infection in cats is increasing, particularly in clade 2.3.4.4b. Their close contact with humans and other animals highlights the need for enhanced surveillance, diagnostics, and One Health strategies to mitigate zoonotic risks. Full article

Respiratory viruses are widespread in the community, affecting both the upper and lower respiratory tract. This review provides an updated synthesis of the epidemiology, pathophysiology, clinical impact, and management of severe respiratory viral infections in critically ill patients, with a focus on immunocompetent adults. The clinical presentation is typically nonspecific, making etiological diagnosis challenging. This limitation has been mitigated by the advent of molecular diagnostics—particularly multiplex PCR (mPCR)—which has not only improved pathogen identification at the bedside but also significantly reshaped our understanding of the epidemiology of respiratory viral infections. Routine mPCR testing has revealed that respiratory viruses are implicated in 30–40% of community-acquired pneumonia hospitalizations and are a frequent trigger of acute decompensations in patients with chronic comorbidities. While some viruses follow seasonal patterns, others circulate year-round. Influenza viruses and Pneumoviridae, including respiratory syncytial virus and human metapneumovirus, remain the principal viral pathogens associated with severe outcomes, particularly acute respiratory failure and mortality. Bacterial co-infections are also common and substantially increase both morbidity and mortality. Despite the growing contribution of respiratory viruses to the burden of critical illness, effective antiviral therapies remain limited. Neuraminidase inhibitors remain the cornerstone of treatment for severe influenza, whereas therapeutic options for other respiratory viruses are largely lacking. Optimizing early diagnosis, refining antiviral strategies, and systematically addressing bacterial co-infections are critical to improving outcomes in patients with severe viral pneumonia. Full article

Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern—both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections. Full article

Background: West Nile Virus [WNV] is a mosquito-borne flavivirus. It has spread globally, causing asymptomatic to severe neurological diseases in humans, with an increased risk in older adults and those with underlying conditions. This review examines WNV’s impact on pregnancy, focusing on maternal and neonatal symptoms and risks. Methods: This systematic review included primary studies from “PUBMED” and “SCOPUS” databases, as well as Google and Google Scholar, conducted in July 2024 using the appropriate keywords. This review adhered to PRISMA guidelines and utilized the Newcastle–Ottawa scale for bias assessment. Results: Seven primary studies were included in the systematic review. Fever was the predominating symptom, including neurological manifestations, respiratory symptoms, myalgia, weakness, nausea, vomiting, and rashes. Delivery, in most cases, progressed without any complications, while no infection was noted. Most of the neonates had a normal Apgar score, and their developmental functions did not seem to be affected. Even though, antibodies against WNV were detected in breast milk, no association with transmission to the neonate was observed. Conclusions: WNV infection is mostly associated with favorable outcomes during pregnancy. However, larger cohorts are needed to confirm our conclusions. Prompt diagnosis and public health surveillance are pivotal to eliminate disease transmission. Full article

Bovine respiratory syncytial virus (BRSV) is an economically important pathogen of cattle and contributes to the bovine respiratory disease complex (BRDC). Despite individual studies investigating BRSV prevalence, risk factors, and detection methodologies, a systematic review and meta-analysis have been lacking. The aim of the current study was to conduct a systematic review and meta-analysis to determine the prevalence and detection rate of BRSV and identify associated risk factors. Additionally, the study aimed to explore the variability in BRSV prevalence based on different detection methods and associated risk factors. Adhering to PRISMA guidelines, data from three databases—Web of Science, PubMed, and Scopus—were systematically retrieved, screened and extracted. Out of 2790 initial studies, 110 met the inclusion criteria. The study found that prevalence and detection rates varied based on the detection methods used (antibody, antigen, and nucleic acid), study populations, production systems, and geographic locations. Findings were reported as a pooled proportion. The pooled proportion, hereafter referred to as prevalence or detection rate, was determined by calculating the ratio of cattle that tested positive for BRSV to the total number of cattle tested. Key findings include a pooled prevalence of 0.62 for antibody-based methods, 0.05 for antigen-based methods, and 0.09 (adjusted to 0.03) for nucleic acid-based methods. Detection rates in BRDC cases also varied, with antibody methods showing a rate of 0.34, antigen methods 0.16, and nucleic acid methods 0.13. The certainty of evidence of the meta-analysis results, assessed using GRADE, was moderate for antibody detection methods and low for antigen and nucleic acid methods. The study identified significant risk factors and trends affecting BRSV prevalence, such as geographical location, herd size, age, and co-infections. The results of the current study showed the complexity of understanding BRSV prevalence in different settings. The variability in BRSV prevalence based on detection methods and associated risk factors, such as geographic location and herd size, highlights the need for tailored approaches to detect and manage BRSV accurately. Full article

Respiratory Syncytial Virus (RSV) is responsible for a considerable burden of respiratory disease among children and older adults. Several prophylactic strategies have recently been introduced. We review the available evidence on the interplay between RSV infection and HIV, looking at the specific role of RSV prophylactic strategies in individuals affected by or exposed to HIV. We conducted a systematic review on the association between HIV infection and RSV incidence and severity. We searched in PubMed/MEDLINE for clinical epidemiological studies covering outcomes such as RSV-associated illness, severity, and mortality in individuals affected by or exposed to HIV. A total of 36 studies met the inclusion criteria and were included, the majority conducted in sub-Saharan Africa. There was no compelling evidence suggesting a higher incidence of RSV illness among HIV-infected people. A higher risk of severe disease was consistent among both HIV-positive and HIV-exposed but uninfected (HEU) children. Case fatality rates were also higher for these groups. Evidence on a differing risk among adults was scarce. HIV-positive pregnant women should be given priority for recently approved RSV vaccination, for protection of their newborns. HIV-infected and HEU infants should be considered risk groups for nirsevimab prophylaxis in their first year of life and possibly beyond. Full article

The most discussed infectious disease is coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Many research endeavors have focused on the effects of the virus on reproductive organs, as these have also been shown to carry the receptors to which the virus attaches. The results of assisted reproductive technology (ART) have been significantly affected by the pandemic, with some in vitro fertilization (IVF) centers being closed due to the risk of further spread of the disease. According to World Health Organization statistics, 17.5% of adults worldwide suffered from fertility problems in 2023; in other words, one in six people in the world have reproductive health problems. As infertility is a growing problem in the modern world and new developments in assisted reproduction are always a topic of profound interest, it is important to understand the impact of SARS-CoV-2 on reproductive health. This systematic review aimed to examine studies describing patients undergoing ART procedures with a COVID-19-positive history and to shed light on the recent evidence on the safety of COVID-19 vaccination in the ART context. A meta-analysis was conducted to confirm the results of the systematic review. The results showed a significant difference in clinical pregnancy rates between the vaccinated and unvaccinated groups and an increased miscarriage rate in those with a COVID-19-positive history. However, no significant difference in clinical pregnancy and birth rates was found in participants with a previous COVID-19 infection. The results show that further studies and research are needed, even though the spread and impact of the virus have decreased. Evidence-based information for individuals and couples undergoing infertility treatment is vital to enable informed decision-making. Full article

An increasing base of evidence suggests that respiratory syncytial virus (RSV) infections may be associated with neurological complications. In accord with the PRISMA statement, we performed a systematic review and meta-analysis on the occurrence of encephalitis and encephalopathy associated with documented RSV infections. PubMed, Embase, and Scopus databases were searched for eligible observational studies published up to 10 April 2024. Raw data included the occurrence of RSV infections among cases of encephalitis and/or encephalopathy and cases of encephalitis and/or encephalopathy among series of RSV infections. Data were pooled in a random effects model. Case reports were also collected, and their data pooled as a cumulative series. Heterogeneity was assessed using the I² measure, while reporting bias was assessed by means of funnel plots and regression analysis. A total of 15 studies for a total of 7719 RSV infections and 1631 cases of encephalitis were analyzed. Moreover, 27 case reports and case series were retrieved, for a total of 84 individual cases of encephalitis/encephalopathy occurring during a documented RSV infection. A pooled prevalence of 2.20 cases of encephalitis/encephalopathy per 100 RSV cases (I² = 99%) was calculated, while a prevalence of RSV infections among cases of encephalitis/encephalopathy was estimated to 3.53 per 100 cases for studies on respiratory specimens (I² = 48%) and 0.37 per cases on central nervous system (CNS) specimens (I² = 0%). Detection of RSV within the CNS was relatively rare (17.86% of pooled case reports), being associated with male gender (adjusted odds ratio [aOR] 5.021, 95% confidence interval [95%CI] 1.104 to 22.831) and recovery with long-term sequelae (aOR 5.699, 95%CI 1.152; 28.183). Case fatality ratio was estimated to be 0.43 per 100 cases on observational studies and 10.71% in case reports, a difference likely due to publication bias. In summary, RSV represented a not frequent but notable cause of encephalitis/encephalopathy in adults and children. The paucity of available studies not only recommends a cautious appraisal of our results but stresses the clinical significance of future studies on incident cases of encephalitis and/or encephalopathy. Full article

The epidemiology of different respiratory viral infections is believed to be affected by prior viral infections in addition to seasonal effects. This PROSPERO-registered systematic review identified 7388 studies, of which six met our criteria to answer the question specifically. The purpose of this review was to compare the prevalence of sequential viral infections in those with previously documented positive versus negative swabs. The pooled prevalence of sequential viral infections over varying periods from 30–1000 days of follow-up was higher following a negative respiratory viral swab at 0.15 than following a positive swab at 0.08, indicating the potential protective effects of prior respiratory viral infections. However, significant heterogeneity and publication biases were noted. There is some evidence, albeit of low quality, of a possible protective effect of an initial viral infection against subsequent infections by a different virus, which is possibly due to broad, nonspecific innate immunity. Future prospective studies are needed to validate our findings. Full article

A systematic review with a meta-analysis was performed to gather available evidence on the effectiveness of monoclonal antibody nirsevimab in the prevention of lower respiratory tract diseases (LRTDs) due to respiratory syncytial virus (RSV) in children and newborns (CRD42024540669). Studies reporting on real-world experience and randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) until 1 May 2024. Our analysis included five RCTs, seven real-world reports, and one official report from the health authorities. Due to the cross-reporting of RCTs and the inclusion of multiple series in a single study, the meta-analysis was performed on 45,238 infants from 19 series. The meta-analysis documented a pooled immunization efficacy of 88.40% (95% confidence interval (95% CI) from 84.70 to 91.21) on the occurrence of hospital admission due to RSV, with moderate heterogeneity (I² 24.3%, 95% CI 0.0 to 56.6). Immunization efficacy decreased with the overall length of the observation time (Spearman’s r = −0.546, p = 0.016), and the risk of breakthrough infections was substantially greater in studies with observation times ≥150 days compared to studies lasting <150 days (risk ratio 2.170, 95% CI 1.860 to 2.532). However, the effect of observation time in meta-regression analysis was conflicting (β = 0.001, 95% CI −0.001 to 0.002; p = 0.092). In conclusion, the delivery of nirsevimab was quite effective in preventing hospital admissions due to LRTDs. However, further analyses of the whole RSV season are required before tailoring specific public health interventions. Full article

N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important etiological factors of lower respiratory tract infections, and exposure to air pollution appears to be additionally associated with higher RSV incidence and disease severity. We aimed to systematically review the existing literature to determine which molecular mechanisms mediate the effects of NAC in an RSV infection and air pollution, and to identify the knowledge gaps in this field. A search for original studies was carried out in three databases and a calibrated extraction grid was used to extract data on the NAC treatment (dose, timing), the air pollutant type, and the most significant mechanisms. We identified only 28 studies conducted in human cellular models (n = 18), animal models (n = 7), and mixed models (n = 3). NAC treatment improves the barrier function of the epithelium damaged by RSV and air pollution, and reduces the epithelial permeability, protecting against viral entry. NAC may also block RSV-activated phosphorylation of the epidermal growth factor receptor (EGFR), which promotes endocytosis and facilitates cell entry. EGFR also enhances the release of a mucin gene, MUC5AC, which increases mucus viscosity and causes goblet cell metaplasia; the effects are abrogated by NAC. NAC blocks virus release from the infected cells, attenuates the cigarette smoke-induced shift from necrosis to apoptosis, and reverses the block in IFN-γ-induced antiviral gene expression caused by the inhibited Stat1 phosphorylation. Increased synthesis of pro-inflammatory cytokines and chemokines is induced by both RSV and air pollutants and is mediated by the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that are activated in response to oxidative stress. MCP-1 (monocyte chemoattractant protein-1) and RANTES (regulated upon activation, expressed and secreted by normal T cells) partially mediate airway hyperresponsiveness (AHR), and therapeutic (but not preventive) NAC administration reduces the inflammatory response and has been shown to reduce ozone-induced AHR. Oxidative stress-induced DNA damage and cellular senescence, observed during RSV infection and exposure to air pollution, can be partially reversed by NAC administration, while data on the emphysema formation are disputed. The review identified potential common molecular mechanisms of interest that are affected by NAC and may alleviate both the RSV infection and the effects of air pollution. Data are limited and gaps in knowledge include the optimal timing or dosage of NAC administration, therefore future studies should clarify these uncertainties and verify its practical use. Full article

Respiratory diseases, including respiratory syncytial virus (RSV) infections, are common reasons for seeking healthcare among refugees and asylum seekers. A systematic review with meta-analysis was designed to appraise all the available evidence on RSV infections among individuals in refugee camps. Three medical databases (PubMed, Embase, and Scopus) as well as the preprint repository medRxiv.org were searched for eligible observational studies, and the collected cases were pooled in a random-effects meta-analysis model. Heterogeneity was assessed using the I² statistics. Funnel plots and a regression analysis were calculated for analyzing reporting bias. Eventually, six studies were retrieved from three areas (Bangladesh, Thailand, and Kenya), with pooled estimates of 129.704 cases per 1000 samples (95% CI 66.393 to 237.986) for RSV compared to 110.287 per 1000 people for influenza A (95% CI 73.186 to 162.889), 136.398 cases per 1000 people (95% CI 84.510 to 212.741) for human adenovirus (HAdV), 69.553 per 1000 people (95% CI 49.802 to 96.343) for parainfluenzavirus (PIFV), and 60.338 per 1000 people (95% CI 31.933 to 111.109) for human metapneumovirus (hMPV). Using influenza A as a reference group, the risk for a positive specimen was greater for RSV (relative risk [RR] 1.514, 95% CI 1.396 to 1.641) and HAdV (RR 1.984, 95% CI 1.834 to 2.146) and lower for influenza B (RR 0.276, 95% CI: 0.239 to 0.319), PIFV (RR: 0.889, 95% CI 0.806 to 0.981), and hMPV (RR 0.594, 95% CI 0.534 to 0.662). In summary, high rates of RSV infections were documented among individuals sheltered in refugee camps, stressing the importance of specifically designed preventive strategies. Full article

Human Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infections. Usually associated with infants and children, an increasing amount of evidence suggests that RSV can cause substantial morbidity and mortality in immunocompromised individuals, including recipients of bone marrow transplantation (BMT). The present systematic review was therefore designed in accordance with the PRISMA guidelines to collect available evidence about RSV infections in BMT recipients. Three medical databases (PubMed, Embase, and MedRxiv) were therefore searched for eligible observational studies published up to 30 September 2023 and collected cases were pooled in a random-effects model. Heterogeneity was assessed using I² statistics. Reporting bias was assessed by means of funnel plots and regression analysis. Overall, 30 studies were retrieved, including 20,067 BMT cases and 821 RSV infection episodes. Of them, 351 were lower respiratory tract infections, and a total of 78 RSV-related deaths were collected. A pooled attack rate of 5.40% (95% confidence interval [95%CI] 3.81 to 7.60) was identified, with a corresponding incidence rate of 14.77 cases per 1000 person-years (95%CI 9.43 to 20.11), and a case fatality ratio (CFR) of 7.28% (95%CI 4.94 to 10.60). Attack rates were higher in adults (8.49%, 95%CI 5.16 to 13.67) than in children (4.79%, 95%CI 3.05 to 7.45), with similar CFR (5.99%, 95%CI 2.31 to 14.63 vs. 5.85%, 95%CI 3.35 to 10.02). By assuming RSV attack rates as a reference group, influenza (RR 0.518; 95%CI 0.446 to 0.601), adenovirus (RR 0.679, 95%CI 0.553 to 0.830), and human metapneumovirus (RR 0.536, 95%CI 0.438 to 0.655) were associated with a substantially reduced risk for developing corresponding respiratory infection. Despite the heterogeneous settings and the uneven proportion of adult and pediatric cases, our study has identified high attack rates and a substantial CFR of RSV in recipients of BMT, stressing the importance of specifically tailored preventive strategies and the need for effective treatment options. Full article