Rhinoviruses (RVs) and respiratory enteroviruses (EVs) are leading causes of upper respiratory tract infections and among the most frequent infectious agents in humans worldwide. Both are classified in the Enterovirus genus within the Picornaviridae family and they have been assigned to seven distinct species, RV-A, B, C and EV-A, B, C, D. As viral infections of public health significance, they represent an important financial burden on health systems worldwide. However, the lack of efficient antiviral treatment or vaccines against these highly prevalent pathogens prevents an effective management of RV-related diseases. Current advances in molecular diagnostic techniques have revealed the presence of RV in the lower respiratory tract and its role in lower airway diseases is increasingly reported. In addition to an established etiological role in the common cold, these viruses demonstrate an unexpected capacity to spread to other body sites under certain conditions. Some of these viruses have received particular attention recently, such as EV-D68 that caused a large outbreak of respiratory illness in 2014, respiratory EVs from species C, or viruses within the newly-discovered RV-C species. This review provides an update of the latest findings on clinical and fundamental aspects of RV and respiratory EV, including a summary of basic knowledge of their biology.

Growth differentiation factor 15 (GDF-15) is a transforming growth factor (TGF)-β superfamily cytokine that plays a central role in metabolism regulation. Produced in response to mitochondrial stress, tissue damage or hypoxia, this cytokine has emerged as one of the strongest predictors of disease severity during inflammatory conditions, cancers and infections. Reports suggest that GDF-15 plays a tissue protective role via sympathetic and metabolic adaptation in the context of mitochondrial damage, although the exact mechanisms involved remain uncertain. In this review, we discuss the emergence of GDF-15 as a distinctive marker of viral infection severity, especially in the context of COVID-19. We will critically review the role of GDF-15 as an inflammation-induced mediator of disease tolerance, through metabolic and immune reprogramming. Finally, we discuss potential mechanisms of GDF-15 elevation during COVID-19 cytokine storm and its limitations. Altogether, this cytokine seems to be involved in disease tolerance to viral infections including SARS-CoV-2, paving the way for novel therapeutic interventions.

The intestinal epithelial layer serves as a physical and functional barrier between the microbiota in the lumen and immunologically active submucosa. Th17 T-cell function protects the gut epithelium from aggression from microbes and their by-products. Loss of barrier function has been associated with enhanced translocation of microbial products which act as endotoxins, leading to local and systemic immune activation. Whereas the inflammatory role of LPS produced by Gram-negative bacteria has been extensively studied, the role of fungal products such as β-D-glucan remains only partially understood. As HIV infection is characterized by impaired gut Th17 function and increased gut permeability, we critically review mechanisms of immune activation related to fungal translocation in this viral infection. Additionally, we discuss markers of fungal translocation for diagnosis and monitoring of experimental treatment responses. Targeting gut barrier dysfunction and reducing fungal translocation are emerging strategies for the prevention and treatment of HIV-associated inflammation and may prove useful in other inflammatory chronic diseases.

In patients with Kaposi’s sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects.

Letermovir prophylaxis in allogeneic hematopoietic cell transplant recipients significantly reduces the incidence of clinically significant cytomegalovirus infection. However, breakthrough infections still occur despite adequate prophylaxis. In the present retrospective cohort study, we identified clinically relevant predictive factors for clinically significant CMV breakthrough infection during letermovir prophylaxis. Low‐grade CMV replication (21–149 IU/ml), both at the time of letermovir initiation or during prophylaxis, was a significant risk factor for breakthrough clinically significant CMV infection. In addition, development of acute gastrointestinal graft‐versus‐host disease was significantly associated with breakthrough infection. Altogether these findings could call clinicians' attention to closer CMV monitoring and allow for prompt preemptive treatment initiation.