Next-generation treatments: Immunotherapy and advanced therapies for COVID-19.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 following prior outbreaks of coronaviruses like SARS and MERS in recent decades, underscoring their high potential of infectivity in humans. Insights from previous outbreaks of SARS and MERS have played a significant role in developing effective strategies to mitigate the global impact of SARS-CoV-2. As of January 7, 2024, there have been 774,075,242 confirmed cases of COVID-19 worldwide. To date, 13.59 billion vaccine doses have been administered, and there have been 7,012,986 documented fatalities (https://www.who.int/) Despite significant progress in addressing the COVID-19 pandemic, the rapid evolution of SARS-CoV-2 challenges human defenses, presenting ongoing global challenges. The emergence of new SARS-CoV-2 lineages, shaped by mutation and recombination processes, has led to successive waves of infections. This scenario reveals the need for next-generation vaccines as a crucial requirement for ensuring ongoing protection against SARS-CoV-2. This demand calls for formulations that trigger a robust adaptive immune response without leading the acute inflammation linked with the infection. Key mutations detected in the Spike protein, a critical target for neutralizing antibodies and vaccine design -specifically within the Receptor Binding Domain region of Omicron variant lineages (B.1.1.529), currently dominant worldwide, have intensified concerns due to their association with immunity evasion from prior vaccinations and infections. As the world deals with this evolving threat, the narrative extends to the realm of emerging variants, each displaying new mutations with implications that remain largely misunderstood. Notably, the JN.1 Omicron lineage is gaining global prevalence, and early findings suggest it stands among the immune-evading variants, a characteristic attributed to its mutation L455S. Moreover, the detrimental consequences of the novel emergence of SARS-CoV-2 lineages bear a particularly critical impact on immunocompromised individuals and older adults. Immunocompromised individuals face challenges such as suboptimal responses to COVID-19 vaccines, rendering them more susceptible to severe disease. Similarly, older adults have an increased risk of severe disease and the presence of comorbid conditions, find themselves at a heightened vulnerability to develop COVID-19 disease. Thus, recognizing these intricate factors is crucial for effectively tailoring public health strategies to protect these vulnerable populations. In this context, this review aims to describe, analyze, and discuss the current progress of the next-generation treatments encompassing immunotherapeutic approaches and advanced therapies emerging as complements that will offer solutions to counter the disadvantages of the existing options. Preliminary outcomes show that these strategies target the virus and address the immunomodulatory responses associated with COVID-19. Furthermore, the capacity to promote tissue repair has been demonstrated, which can be particularly noteworthy for immunocompromised individuals who stand as vulnerable actors in the global landscape of coronavirus infections. The emerging next-generation treatments possess broader potential, offering protection against a wide range of variants and enhancing the ability to counter the impact of the constant evolution of the virus. Furthermore, advanced therapies are projected as potential treatment alternatives for managing Chronic Post-COVID-19 syndromeand addressing its associated long-term complications.

The Multifaceted Role of Annexin A1 in Viral Infections.

Dysregulated inflammatory responses are often correlated with disease severity during viral infections. Annexin A1 (AnxA1) is an endogenous pro-resolving protein that timely regulates inflammation by activating signaling pathways that culminate with the termination of response, clearance of pathogen and restoration of tissue homeostasis. Harnessing the pro-resolution actions of AnxA1 holds promise as a therapeutic strategy to control the severity of the clinical presentation of viral infections. In contrast, AnxA1 signaling might also be hijacked by viruses to promote pathogen survival and replication. Therefore, the role of AnxA1 during viral infections is complex and dynamic. In this review, we provide an in-depth view of the role of AnxA1 during viral infections, from pre-clinical to clinical studies. In addition, this review discusses the therapeutic potential for AnxA1 and AnxA1 mimetics in treating viral infections.

Immunometabolic Signature during Respiratory Viral Infection: A Potential Target for Host-Directed Therapies.

RNA viruses are known to induce a wide variety of respiratory tract illnesses, from simple colds to the latest coronavirus pandemic, causing effects on public health and the economy worldwide. Influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RhV), and coronavirus (CoV) are some of the most notable RNA viruses. Despite efforts, due to the high mutation rate, there are still no effective and scalable treatments that accompany the rapid emergence of new diseases associated with respiratory RNA viruses. Host-directed therapies have been applied to combat RNA virus infections by interfering with host cell factors that enhance the ability of immune cells to respond against those pathogens. The reprogramming of immune cell metabolism has recently emerged as a central mechanism in orchestrated immunity against respiratory viruses. Therefore, understanding the metabolic signature of immune cells during virus infection may be a promising tool for developing host-directed therapies. In this review, we revisit recent findings on the immunometabolic modulation in response to infection and discuss how these metabolic pathways may be used as targets for new therapies to combat illnesses caused by respiratory RNA viruses.