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.

Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome.

Background: Long COVID (coronavirus disease 2019) 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. In this report, we propose a model for the pathophysiology of the long COVID presentation based on increased proinflammatory cytokine production that results from the persistence of the SARS-CoV-2 virus or one of its molecular components. Associated with this hyperproduction of inflammatory cytokines is a heightened activity of nuclear factor κ B (NF-κB) and p38 mitogen-activated protein kinase signaling pathways that regulate cytokine production. Objective: The purpose of the present report was to review the causes of long COVID syndrome and suggest ways that can provide a basis for a better understanding of the clinical symptomatology for the of improved diagnostic and therapeutic procedures for the condition. Methods: Extensive research was conducted in medical literature data bases by applying terms such as "long COVID" associated with "persistence of the SARS-CoV-2 virus" "spike protein' "COVID-19" and "biologic therapies." Results and Conclusions: In this model of the long COVID syndrome, the persistence of SARS-CoV-2 is hypothesized to trigger a dysregulated immune system with subsequent heightened release of proinflammatory cytokines that lead to chronic low-grade inflammation and multiorgan symptomatology. The condition seems to have a genetic basis, which predisposes individuals to have a diminished immunologic capacity to completely clear the virus, with residual parts of the virus persisting. This persistence of virus and resultant hyperproduction of proinflammatory cytokines are proposed to form the basis of the syndrome.

COVID-19 vaccines and vaccine hesitancy: Role of the allergist/immunologist in promotion of vaccine acceptance.

Background: Vaccine hesitancy has been defined as a delay in acceptance or refusal of vaccines, despite the availability of vaccine services. In the past, despite an impressive record of vaccine effectiveness in the United States, several factors have contributed to a decreased acceptance of vaccines that has resulted in outbreaks of infectious diseases, e.g., measles. More recently, vaccine hesitancy has spread to coronavirus disease 2019 (COVID-19) vaccines. There are many causes of vaccine hesitancy, such as misinformation, fallacies, and myths, that have contributed to vaccine hesitancy. Objective: The purpose of the present report is to address the many causes of vaccine hesitancy and to suggest ways that the allergist/immunologist can be involved in the promotion of vaccine acceptance. Methods: The current COVID-19 vaccines were reviewed, together with their mechanisms(s) of action and adverse reactions to them. Results: The many causes of vaccine hesitancy include many doubts and concerns related to COVID-19 vaccines as well as a diminished level of confidence and trust by segments of the public in the nation's leaders in government, medical, and business communities, that those groups once enjoyed. Conclusion: Vaccination with COVID-19 vaccines is the only way that COVID-19 will be eliminated or at least controlled today, and vaccine hesitancy is the potential nemesis. The present report describes how the allergist/immunologist not only plays a major role in the delivery of specialized therapy of COVID-19 but also in educating the public with regard to the importance of COVID-19 vaccines, in dispelling misinformation, and in promoting trust for vaccine acceptance but must be informed with the most accurate and current information to do so.

COVID-19 in children: Pathogenesis and current status.

Background: Since its initial description in December 2019 in Wuhan, China, coronavirus disease 2019 (COVID-19) has rapidly progressed into a worldwide pandemic, which has affected millions of lives. Unlike the disease in adults, the vast majority of children with COVID-19 have mild symptoms and are largely spared from severe respiratory disease. However, there are children who have significant respiratory disease, and some may develop a hyperinflammatory response similar to that seen in adults with COVID-19 and in children with Kawasaki disease (KD), which has been termed multisystem inflammatory syndrome in children (MIS-C). Objective: The purpose of this report was to examine the current evidence that supports the etiopathogenesis of COVID-19 in children and the relationship of COVID-19 with KD and MIS-C as a basis for a better understanding of the clinical course, diagnosis, and management of these clinically perplexing conditions. Results: The pathogenesis of COVID-19 is carried out in two distinct but overlapping phases of COVID-19: the first triggered by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and the second by the host immune response. Children with KD have fewer of the previously described COVID-19-associated KD features with less prominent acute respiratory distress syndrome and shock than children with MIS-C. Conclusion: COVID-19 in adults usually includes severe respiratory symptoms and pathology, with a high mortality. It has become apparent that children are infected as easily as adults but are more often asymptomatic and have milder disease because of their immature immune systems. Although children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated MIS-C similar to KD.