Addressing global health disparities in the management of RSV infection in infants and children: Strategies for preventing bronchiolitis and post-bronchiolitis recurrent wheezing.

Background: The topic of equitable access to health care and its impact on exacerbating worldwide inequities in child health not only strikes at the heart of our health-care delivery systems but also deeply resonates with our collective social consciences. Nowhere is this better seen on a global scale than in the burden of illness caused by respiratory syncytial virus (RSV) infection, which extracts the most severe morbidity and mortality in infants and children in low- and middle-income countries (LMIC). This report addresses global health disparities that exist in the management of RSV infection in infants and children, and offers strategies for preventing bronchiolitis and postbronchiolitis recurrent wheezing in LMICs. Methods: A systematic literature review was conducted across the PubMed data bases of RSV infection and the socioeconomic impact of bronchiolitis and postbronchiolitis recurrent wheezing in LMICs. Results: The results of the present study address the many issues that deal with the question if prevention of RSV bronchiolitis can mitigate recurrent wheezing episodes and links RSV risks, downstream effects, prevention, malnutrition, and socioeconomic restraints of developing countries with a call for possible global action. Conclusion: The present study stresses the importance of considering the linkage between malnutrition and disease susceptibility because of the known relationships between undernutrition and greater vulnerability to infectious diseases, including RSV infection. These complex interactions between infectious disease and undernutrition also raise issues on the longer-term sequelae of postbronchiolitis recurrent wheezing. This prompts a discussion on whether industrialized countries should prioritize the provision of newly developed monoclonal antibodies and RSV vaccines to LMICs or whether vital nutritional needs should be a first focus. The resolution of these issues will require research and greater international discourse.

The Long Road of Long COVID: Specific Considerations for the Allergist/Immunologist.

Long COVID (coronavirus disease 2019) syndrome, also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a new disorder that can develop after an acute infection with the SARS-CoV-2 virus. The condition is characterized by multiorgan system involvement with a wide range of symptoms that can vary in severity from mild to debilitating. Some of the common symptoms associated with long COVID syndrome include cardiovascular issues such as heart palpitations and chest pain; thrombotic events (eg, blood clotting disorders); metabolic problems (eg, type 2 diabetes); dysautonomia; paroxysmal orthostatic tachycardia syndrome; myalgic encephalomyelitis/chronic fatigue syndrome; reactivation of the Epstein-Barr virus; the presence of autoantibodies; chronic spontaneous urticaria (hives); and connective tissue diseases. Whereas long COVID syndrome can affect individuals from various backgrounds, certain populations may be at higher risk such as individuals of Hispanic and Latino heritage, as well as those with low socioeconomic status, although approximately one-third of affected patients have no known risk factors or preexisting conditions. Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. Whereas vaccination has been the most significant intervention able to decrease the severity of acute SARS-Cov2 infection and curtail deaths, limited data are available related to its modulating effect on long COVID necessitating the need for further investigation. Furthermore, several inflammatory pathways have been proposed for the pathogenesis of long COVID that are the targets for ongoing clinical studies evaluating novel pharmacological agents. The purpose of the present report is to review the many factors associated with long COVID with a focus on those aspects that have relevance to the allergist-immunologist.

The PANDAS/PANS disorders. Is it time for more allergist-immunologists to get involved?

Background: The pediatric autoimmune neurologic disorders associated with streptococcal infections (PANDAS) comprise a group of patients who, after infection with group A ß-hemolytic streptococci (GAS), exhibit a spectrum of neuropsychiatric symptoms that include obsessive thoughts, compulsive behaviors, tics, hyperactivity, inattention, and mild choreiform movements. More recently, a group of patients with a symptom complex similar to PANDAS without evidence of streptococcal etiology was given the acronym pediatric acute-onset neuropsychiatric syndrome (PANS). Despite more than several decades of study and increasing numbers of patients being identified with PANDAS and PANS, there are ongoing controversies, which range from disagreements about specific pathogenetic mechanisms to whether these entities actually exist. Objective: The purpose of this report was to examine the current body of evidence that deals with the relationship(s) of immunologic host responses to infection and putative immunologic mechanisms involved in the pathogenesis of these disorders, to evaluate the effectiveness of anti-inflammatory and immunomodulatory therapies with intravenous immunoglobulin (IVIG), and to consider the extent to which allergist/immunologists might be involved in their management. Methods: An extensive literature review was conducted in medical literature data bases by applying terms such as PANDAS, PAN, autoimmune encephalitis, neuroinflammation, and autoimmune obsessive-compulsive disorders. Results: PANDAS and its later iterative form, PANS, continue to challenge clinicians, patients, and their families. Although the precise reason why these disorders develop remains unknown, both are considered to have an autoimmune basis related to the production of antibodies directed at antigens of the putative causative infectious disease agents that are cross-reactive with antigenic epitopes on selected brain nuclei, which lead to the neuroinflammatory sequelae responsible for the neuropsychiatric symptoms of these conditions, a phenomenon referred to as molecular mimicry. Conclusion: The PANDAS/PANS disorders are a continuing burden for growing numbers of patients, health-care providers, and the global health-care systems, and are a particular challenge for the allergist/immunologist who is increasingly being called upon for their management. Because of the importance of immunologic factors in the pathogenesis and treatment of these conditions with anti-inflammatory and immune-modulating treatments, the allergist/immunologist is well poised to offer consultative care.

The 80th anniversary of Annals of Allergy, Asthma & Immunology (1943-2023).

The year 2023 marks the 80th year of publication of Annals of Allergy, Asthma & Immunology. To celebrate this important milestone, we look back on the history of the journal from its inception to the present day. This special article explores the rationale and people involved in creating the journal and highlights major advances in Annals history. Our celebration of Annals' 80th year of publication concludes with a glimpse into the potential future of Annals.

The third pandemic: The respiratory syncytial virus landscape and specific considerations for the allergist/immunologist.

Background: Since its initial identification in 1956, respiratory syncytial virus (RSV) has been the second most common cause of mortality in infants <6 months of age and a major cause of morbidity and mortality associated with lower respiratory tract infection (LRTI) in older adults (ages >60 years) worldwide. Of particular interest to the allergist/immunologist is a growing body of evidence that suggests an association between LRTI caused by RSV in infants with later-life development of asthma, wheezing, or impaired lung function in adults. Efforts to develop a RSV vaccine have been thwarted for >70 years by the occurrence of enhanced respiratory disease (ERD), an adverse RSV vaccine reaction, in the 1960s, in which more-severe illness occurred on natural infection after vaccination of infants who were RSV naive and with a formalin-inactivated RSV vaccine. Recent advances in knowledge of the structural biology of the RSV surface fusion glycoprotein, however, have revolutionized RSV vaccine development for preventive interventions and have offered, at last, the hope of an effective and safe vaccine for the prevention of RSV disease. Objective: The purpose of this report was to examine the current evidence that supports the epidemiology, disease manifestations, molecular biology, treatments, and new vaccine development of RSV vaccines. Results: The host-immune response to RSV infection is carried out by two distinct but overlapping universes of mucosal and systemic immune systems in which a balanced set of B- and T-cell responses are involved in protective immunity that includes the mucosal immune system in which immunoglobulin A (IgA) prevails and the systemic immune system in which IgG neutralizing antibody predominates. The key to developing an effective vaccine is now thought to be linked to the availability of a stabilized prefusion F protein in the immunizing vaccine, which can perform a dual function of a balanced mucosal and/or systemic immune response as well as an effective antibody specifically directed to critical epitopes on the requisite prefusion F protein. Conclusion: The unfortunate manifestation of RSV ERD that occurred in the 1960s has led to a better understanding of the structural biology of the RSV surface fusion glycoprotein and has provided a basis for the development of more effective and safer RSV vaccines and monoclonal antibody preparations for immunoprophylaxis of the dread effects of RSV disease. There are now a large number of clinical trials in progress that are evaluating these products, which include recombinant vector, subunit, particle-based, live-attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. This article gives an overview of the many aspects of RSV disease and development of virus (RSV) vaccines of particular interest to the allergist/immunologist.

Monkeypox viral infection and disease: A challenge for the allergist-immunologist.

Background: Human monkeypox is a zoonosis caused by the monkeypox virus, an orthopoxvirus and close relative of variola virus, the causative agent of smallpox. The disease was first reported in central Africa in 1970, where it continues to be endemic and has historically affected some of the poorest and most marginalized communities in the world. The condition has recently attracted global attention due to >14,000 cases, including five deaths, reported by the World Health Organization, and a total of 5189 confirmed monkeypox cases in the United States reported by the Centers for Disease Control and Prevention as of July 29, 2022. On July 23, 2022, the World Health Organization declared the current monkeypox outbreak a Public Health Emergency of International Concern. Objective: The purpose of the present report was to review the epidemiology of monkeypox viral infection; its clinical manifestations; and current recommendations for diagnosis, treatment, and use of vaccines for prevention of the disease, with a focus on those aspects that have particular relevance to the allergist/immunologist. Results: Monkeypox was discovered in the early 1970s and, for years, has been well described by researchers in west and central Africa, where the disease has been present for decades. Although this outbreak thus far has mostly affected men who have sex with men, it is possible that the disease could become endemic and could begin spreading in settings where there is close physical contact, which is how the virus is transmitted. Conclusion: Monkeypox is a different viral infection from the coronavirus. Unlike the coronavirus, which is an extremely contagious respiratory pathogen, monkeypox is primarily transmitted through body fluids and/or prolonged skin-to-skin contact. Although the control of monkeypox will require renewed efforts and resources, we have learned much from the past and have the tools to stop this virus from becoming yet another serious illness with which Americans have to contend. The allergist/immunologist can play a significant role.

The mitochondrial complex I proteins of Candida albicans moderate phagocytosis and the production of pro-inflammatory cytokines in murine macrophages and dendritic cells.

Loss of respiratory functions impairs Candida albicans colonization of host tissues and virulence in a murine model of candidiasis. Furthermore, it is known that respiratory inhibitors decrease mannan synthesis and glucan exposure and thereby promotes phagocytosis. To understand the impact of respiratory proteins of C. albicans on host innate immunity, we characterized cell wall defects in three mitochondrial complex I (CI) null mutants (nuo1Δ, nuo2Δ and ndh51Δ) and in one CI regulator mutant (goa1Δ), and we studied the corresponding effects of these mutants on phagocytosis, neutrophil killing and cytokine production by dendritic cells (DCs). We find that reductions of phosphopeptidomannan (PPM) in goa1Δ, nuo1Δ and phospholipomannan (PLM) in nuo2Δ lead to reductions of IL-2, IL-4, and IL-10 but increase of TNF-α in infected DCs. While PPM loss is a consequence of a reduced phospho-Cek1/2 MAPK that failed to promote phagocytosis and IL-22 production in goa1Δ and nuo1Δ, a 30% glucan reduction and a defective Mek1 MAPK response in ndh51Δ lead to only minor changes in phagocytosis and cytokine production. Glucan exposure and PLM abundance seem to remain sufficient to opsonize neutrophil killing perhaps via humoral immunity. The diversity of immune phenotypes in these mutants possessing divergent cell wall defects is further supported by their transcriptional profiles in each infected murine macrophage scenario. Since metabolic processes, oxidative stress-induced senescence, and apoptosis are differently affected in these scenarios, we speculate that during the early stages of infection, host immune cells coordinate their bioactivities based upon a mixture of signals generated during host-fungi interactions.

The long COVID syndrome: A conundrum for the allergist/immunologist.

Background: The long coronavirus disease 2019 (COVID-19) syndrome includes a group of patients who, after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit lingering mild-to-moderate symptoms and develop medical complications that can have lasting health problems. Objective: The purpose of this report was to examine the current body of evidence that deals with the relationship of COVID-19 infection with the long COVID syndrome to define the possible immunologic mechanisms involved in the pathogenesis of long COVID and to describe potential strategies for the diagnosis and clinical management of the condition. Methods: Extensive research was conducted in medical literature data bases by applying terms such as long COVID, post-COVID-19 condition, pathogenesis of long COVID, management of the long COVID syndrome. Results: The post-COVID conditions, a more recent and less anxiety-inducing term for the patient than long COVID or "long haul," is an umbrella term for a wide range of physical and mental health symptoms similar to those seen in patients with the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), experienced by some patients and are present ≥ 4 weeks after SARS-CoV-2 infection. Although the precise reason why long COVID develops is unknown, one of the major causes is thought to be related to chronic inflammation with overproduction of inflammatory cytokines responsible for the symptoms of the disorder. Conclusion: Long COVID is a growing burden for millions of patients, health-care providers, and global health-care systems, and is a particular challenge for the allergist/immunologist. Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. The allergist/immunologist can assist the total health-care team's efforts in providing a comprehensive and coordinated approach to the management of these patients by promoting comprehensive vaccination and rehabilitation and social services that focus on improving physical, mental, and social well-being, and by establishing partnerships with specialists and other health-care professionals who can provide behavioral, lifestyle, and integrative approaches that may have much to offer in helping patients cope with their symptoms.

Salivary and serum IgA and IgG responses to SARS-CoV-2-spike protein following SARS-CoV-2 infection and after immunization with COVID-19 vaccines.

Background: Secretory immunoglobulin A (sIgA) plays an important role in antiviral protective immunity. Although salivary testing has been used for many viral infections, including severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS), its use has not yet been well established with the SARS coronavirus 2 (SARS-CoV-2). Quantification of salivary IgA and IgG antibodies can elucidate mucosal and systemic immune responses after natural infection or vaccination. Here, we report the development and validation of a rapid enzyme-linked immunosorbent assay (ELISA) for anti-SARS-CoV-2 salivary IgA and serum IgG antibodies, and present quantitative results for immunized subjects both prior to or following COVID-19 infections. Objective: Total and serum SARS-CoV-2 spike-specific IgG responses were compared with salivary spike-specific IgA and IgG responses in samples obtained from patients recently infected with SARS-CoV-2 and from subjects recently immunized with COVID-19 vaccines. Methods: A total of 52 paired saliva and serum samples were collected from 26 study participants: 7 subjects after COVID-19 infection and 19 subjects who were uninfected. The ELISA results from these samples were compared with five prepandemic control serum samples. Total IgG and SARS-CoV-2 spike-specific IgG in the serum samples from the subjects who were infected and vaccinated were also measured in a commercial laboratory with an enzyme immunoassay. Results: A wide variation in antibody responses was seen in salivary and serum samples measured by both methods. Three groups of serum total and IgG spike-specific SARS-CoV-2 antibody responses were observed: (1) low, (2) intermediate, and (3) high antibody responders. A correlational analysis of salivary IgA (sIgA) responses with serum IgG concentrations showed a statistical correlation in the low and intermediate antibody responder groups but not in the high group (which we believe was a result of saturation). Conclusion: These preliminary findings suggest measuring salivary and serum IgG and IgA merit further investigation as markers of current or recent SARS-CoV-2 infections.

Measurements of Treg Cell Induction by Candida albicans DNA Using Flow Cytometry.

Microbiota and their metabolites in the human gut regulate a variety of immune cells including regulatory T cells (Treg cells) and cytokine production. The T helper 17 (Th17)/Treg ratio biomarker (Th17/Treg), for example, has been linked to the development and progression of certain inflammatory diseases, insulin resistance, and systemic lupus erythematosus (SLE). Candida albicans is an opportunistic fungal pathogen that also colonizes the gut. T cell reactivity through T helper cells play critical roles in fungal clearance by the host through the secretion of proinflammatory cytokines. While these cytokines are mainly produced by the Th1 and Th17 subsets of T cells, another subset of T cells, the Treg cells, are also induced by antigenic ligands from pathogens that inhibit the responses of other effector T cells during the inflammation. The antigenic ligands for Treg induction have been found to include microbial cell wall polysaccharides (PSA), metabolites like short chain fatty acids (SCFA), or even microbial DNA.