Immunomodulator therapies in pandemics: lessons from COVID-19 and a blueprint for future outbreaks

Background/Objectives: The COVID-19 pandemic resulted in 675 million cases and 6.9 million deaths by 2022. Despite substantial declines in case fatalities following widespread vaccination campaigns, the threat of future coronavirus outbreaks remains a concern. Current treatments for COVID-19 have been repurposed from existing therapies for other infectious and non-infectious diseases. Emerging evidence suggests a role for genetic factors in both susceptibility to SARS-CoV-2 infection and response to treatment. However, comprehensive studies correlating clinical outcomes with genetic variants are lacking. The main aim of our study is the identification of host genetic biomarkers that predict the clinical outcome of COVID-19 pharmacological treatments. Methods: In this study, we present findings from GWAS and candidate gene and pathway enrichment analyses leveraging diverse patient samples from the Spanish Coalition to Unlock Research of Host Genetics on COVID-19 (SCOURGE), representing patients treated with immunomodulators (n = 849), corticoids (n = 2202), and the combined cohort of both treatments (n = 2487) who developed different outcomes. We assessed various phenotypes as indicators of treatment response, including survival at 90 days, admission to the intensive care unit (ICU), radiological affectation, and type of ventilation. Results: We identified significant polymorphisms in 16 genes from the GWAS and candidate gene studies (TLR1, TLR6, TLR10, CYP2C19, ACE2, UGT1A1, IL-1α, ZMAT3, TLR4, MIR924HG, IFNG-AS1, ABCG1, RBFOX1, ABCB11, TLR5, and ANK3) that may modulate the response to corticoid and immunomodulator therapies in COVID-19 patients. Enrichment analyses revealed overrepresentation of genes involved in the innate immune system, drug ADME, viral infection, and the programmed cell death pathways associated with the response phenotypes. Conclusions: Our study provides an initial framework for understanding the genetic determinants of treatment response in COVID-19 patients, offering insights that could inform precision medicine approaches for future epidemics.

Influenza infection, SARS, MERS and COVID-19: Cytokine storm – The common denominator and the lessons to be learned

Seroconversion and indolent course of COVID-19 in patients with multiple sclerosis treated with fingolimod and teriflunomide

ABSTRACTIntroduction: Seasonal influenza epidemics and periodic pandemics are important causes of morbidity and mortality. Influenza transmits predominantly by respiratory droplets and fomites but opportunistic airborne transmission may occur in the hospital setting due to overcrowding, poor compliance with infection control measures, and performance of aerosol-generating procedures.Areas covered: This article reviews the risk factors of nosocomial influenza outbreaks and discusses clinical, diagnostic, and treatment aspects of seasonal and avian influenza to facilitate hospital preparations for future influenza outbreaks. Literature search was conducted through PubMed of relevant peer-reviewed full papers in English journals with inclusion of relevant publications by the WHO and US CDC.Expert opinion: Accurate and rapid identification of an influenza outbreak is important to facilitate patient care and prevent nosocomial transmission. Timely treatment with a neuraminidase inhibitor (NAI) for adults hospitalized with severe influenza is associated with lower mortality and better clinical outcomes. Baloxavir, a polymerase endonuclease inhibitor, offers a new treatment alternative and its role in combination with NAI for treatment of severe influenza is being investigated. High-dose systemic corticosteroids are associated with worse outcomes in patients with severe influenza. It is important to develop more effective antiviral and immuno-modulating therapies for the treatment of influenza infections.

Mosquito-borne viruses (MBVs) are a major global health threat, causing significant morbidity and mortality. MBVs belong to several distinct viral families, each with unique characteristics. The primary families include Flaviviridae (e.g., Dengue, Zika, West Nile, Yellow Fever, Japanese Encephalitis), transmitted predominantly by Aedes and Culex mosquitoes; Togaviridae, which consists of the genus Alphavirus (e.g., Chikungunya, Eastern and Western Equine Encephalitis viruses), also transmitted by Aedes and Culex; Bunyaviridae (recently reorganized), containing viruses like Rift Valley Fever and Oropouche virus, transmitted by mosquitoes and sometimes sandflies; and Reoviridae, which includes the genus Orbivirus (e.g., West Nile and Bluetongue viruses), primarily affecting animals and transmitted by mosquitoes and sandflies. Despite extensive research, effective antiviral treatments for MBVs remain scarce, and current therapies mainly provide symptomatic relief and supportive care. This review examines the viral components and cellular and immune factors involved in the life cycle of MBVs. It also highlights recent advances in antiviral strategies targeting host factors such as lipid metabolism, ion channels, and proteasomes, as well as viral targets like NS2B-NS3 proteases and nonstructural proteins. Additionally, it explores immunomodulatory therapies to enhance antiviral responses and emphasizes the potential of drug repurposing, bioinformatics, artificial intelligence, and deep learning in identifying novel antiviral candidates. Continued research is crucial in mitigating MBVs’ impact and preventing future outbreaks.