Xuan Liu

The poor prognosis observed in elderly individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains a serious clinical burden and the underlying mechanism is unclear, which necessities detailed investigation of disease characteristics and research for efficient countermeasures. To simulate lethal coronavirus disease 2019 (COVID‐19) in senescent human patients, 80‐week‐old male hamsters are intranasally inoculated with different doses of SARS‐CoV‐2 Omicron BA.5 variant. Exposure to a low dose of the Omicron BA.5 variant results in early activation of the innate immune response, followed by rapid viral clearance and minimal lung damage. However, a high dose of BA.5 results in impaired interferon signaling, cytokine storm, uncontrolled viral replication, and severe lung injury. To decrease viral load and reverse the deterioration of COVID‐19, a new bio‐mimic decoy called CoVR‐MV is used as a preventive or therapeutic agent. Administration of CoVR‐MV as a preventive or therapeutic intervention in the early stages of infection can effectively suppress viral load, regulate the immune response, and rescue animals from death and critical illness. These findings underscore the risk associated with SARS‐CoV‐2 Omicron BA.5 exposure in senescent hamsters and highlight the importance of early intervention to prevent disease progression.

Studies have reported variable effects of sex hormones on serious diseases. Severe disease and mortality rates in COVID‐19 show marked gender differences that may be related to sex hormones. Sex hormones regulate the expression of the viral receptors ACE2 and TMPRSS2, which affect the extent of viral infection and consequently cause variable outcomes. In addition, sex hormones have complex regulatory mechanisms that affect the immune response to viruses. These hormones also affect metabolism, leading to visceral obesity and severe disease can result from complications such as thrombosis. This review presents the latest researches on the regulatory functions of hormones in viral receptors, immune responses, complications as well as their role in COVID‐19 progression. It also discusses the therapeutic possibilities of these hormones by reviewing the recent findings of clinical and assay studies.

Emerging and re‐emerging viral pandemics have emerged as a major public health concern. Highly pathogenic coronaviruses, which cause severe respiratory disease, threaten human health and socioeconomic development. Great efforts are being devoted to the development of safe and efficacious therapeutic agents and preventive vaccines to combat them. Nevertheless, the highly mutated virus poses a challenge to drug development and vaccine efficacy, and the use of common immunomodulatory agents lacks specificity. Benefiting from the burgeoning intersection of biological engineering and biotechnology, membrane‐derived vesicles have shown superior potential as therapeutics due to their biocompatibility, design flexibility, remarkable bionics, and inherent interaction with phagocytes. The interactions between membrane‐derived vesicles, viruses, and the immune system have emerged as a new and promising topic. This review provides insight into considerations for developing innovative antiviral strategies and vaccines against SARS‐CoV‐2. First, membrane‐derived vesicles may provide potential biomimetic decoys with a high affinity for viruses to block virus‐receptor interactions for early interruption of infection. Second, membrane‐derived vesicles could help achieve a balanced interplay between the virus and the host's innate immunity. Finally, membrane‐derived vesicles have revealed numerous possibilities for their employment as vaccines.

Studies report variable effects of sex hormones on serious diseases. Severe disease and mortality rates in COVID-19 show marked gender differences that may be related to sex hormones. Sex hormones regulate the expression of the viral receptors ACE2 and TMPRSS2, which affect the extent of viral infection and consequently cause variable outcomes. In addition, sex hormones have complex regulatory mechanisms that affect the immune response to viruses. These hormones also affect metabolism through obesity, and severe disease can result from complications such as thrombosis. This review presents the latest research on the regulatory functions of hormones in viral receptors, immune responses, complications as well as their role in COVID-19 progression. It also discusses the therapeutical possibilities of these hormones by reviewing the recent findings of clinical and assay studies.

Vaccination is the most cost-effective means in the fight against infectious diseases. Various kinds of vaccines have been developed since the outbreak of COVID-19, some of which have been approved for clinical application. Though vaccines available achieved partial success in protecting vaccinated subjects from infection or hospitalization, numerous efforts are still needed to end the global pandemic, especially in the case of emerging new variants. Safe and efficient vaccines are the key elements to stop the pandemic from attacking the world now; novel and evolving vaccine technologies are urged in the course of fighting (re)-emerging infectious diseases. Advances in biotechnology offered the progress of vaccinology in the past few years, and lots of innovative approaches have been applied to the vaccine design during the ongoing pandemic. In this review, we summarize the state-of-the-art vaccine strategies involved in controlling the transmission of SARS-CoV-2 and its variants. In addition, challenges and future directions for rational vaccine design are discussed.

The rational design of tumor microenvironment (TME)‐activated nanomedicine is driving a new direction in tumor immunology. Furthermore, the novel therapeutic mode of ultrasound‐triggered sonodynamic therapy (SDT) has been proven to specifically activate the immune response. Herein, a well‐defined covalent organic framework (COF) with sonosensitive properties is synthesized through experimental and theoretical verification, followed by the efficient loading of the toll‐like receptor agonist (Poly(I:C)) and in situ growth of paramagnetic transitional metallic oxide of manganese bioxide (MnO₂). The MnO₂‐Poly(I:C)@COF shell can reverse the reductive TME by consuming glutathione (GSH) to release Mn²⁺, simultaneously generating marked magnetic resonance imaging signals for real‐time guidance. Importantly, the MnO₂ acts as an enzyme‐like nano‐catalyst to promote TME‐overexpressed hydrogen peroxide (H₂O₂) and produce oxygen, facilitating SDT‐induced reactive oxygen species production, and inducing immunogenic cell death, thereby boosting immune engine and triggering abundant neoantigen exposure. With the powerful assistance of immunological agents Mn²⁺ and Poly(I:C), the triggered immune engine is amplified by refueling the engine (stepping on the accelerator) to reduce the immunosuppressive state. Overall, this study improves the synthesis of multifunctional COF and expands its application. The developed nano‐sonosensitizer system provides a paradigm to enhance SDT‐based high‐performance multifunctional sonosensitizers, and this SDT‐mediated strong tumor‐suppressive efficiency and activated immune effect represent a promising combinatorial therapeutic strategy for cancer therapy.