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Summary: Adjuvants, as the name indicates, are adjoined material aimed to assist in functioning as when added to vaccines they are meant to boost the effect and strongly stimulate the immune system. The response of the immune system can be unpredictable, and the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was developed to address possible adverse reactions of an autoimmune and inflammatory type that may be caused by adjuvants. While ASIA, as a syndrome, was coined and defined in 2011; reports describing patients with vague and nonspecific clinical symptoms following vaccinations appeared much earlier. In other words, ASIA came to define, arrange, and unite the variety of symptoms, related to autoimmunity, caused not by the vaccine itself, rather by the adjuvant part of the vaccine such as aluminum, among others. Accordingly, the introduction of ASIA enabled better understanding, proper diagnosis, and early treatment of the disorder. Furthermore, ASIA was shown to be associated with almost all body systems and various rheumatic and autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, and systemic sclerosis. In addition, the correlation between COVID-19 and ASIA was noticed during the pandemic. In this review, we summarized the reported effects of adjuvants and medical literature before and after ASIA was defined, the several ways ASIA can manifest and impact different systems of the body, and the incidences of ASIA during the COVID-19 pandemic. It is important to clarify, that vaccines are among, if not the, most effective means of fighting infectious diseases however, we believe that vaccines manufacturing is not above criticism, particularly when it comes to added substances possessing a risk of side effects. Adjuvants such as aluminum, mineral oils, and silicone are added to vaccines in order to trigger a stronger immune response. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was introduced in 2011 to address nonspecific symptoms and disorders appearing following vaccinations, which in fact were reported by many papers before the introduction of the syndrome. During the pandemic of COVID-19, a correlation between ASIA, COVID-19, and COVID-19 vaccines has been reported. [ABSTRACT FROM AUTHOR]

Summary: The factors responsible for the spectrum of coronavirus 19 (COVID‐19) disease severity and the genesis and nature of protective immunity against COVID‐19 remain elusive. Multiple studies have investigated the immune responses to COVID‐19 in various populations, including those without evidence of COVID‐19 infection. Information regarding innate and adaptive immune responses to the novel severe respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has evolved rapidly. Data are accumulating defining disease phenotypes that aid in rational and informed development of new therapeutic approaches for the treatment of patients infected with SARS‐CoV‐2 and the development of novel vaccines. In this paper, data on important innate immune responses are summarized, including cytokines, specifically interleukin (IL)‐6 and complement, and potential treatments are explored. Adaptive immune responses and derivative therapeutics such as monoclonal antibodies directed at spike proteins are also examined. Finally, data on real‐time assessments of adaptive immune responses are explored, which include CD4+/CD8+ T cells, natural killer (NK) T cells, memory B cells and T follicular cells with specificities for COVID‐19 peptides in infected and normal individuals. Data of two novel vaccines have been released, both showing > 95% efficacy in preventing SARS‐CoV‐2 infection. Analysis of humoral and cellular responses to the vaccines will determine the robustness and durability of protection. In addition, long‐term assessment of SARS‐CoV‐2 memory B and T cell‐mediated immune responses in patients recovering from an infection or those with cross‐reactive immunological memory will help to define risk for future SARS‐CoV infections. Finally, patients recovering from SARS‐CoV‐2 infection may experience prolonged immune activation probably due to T cell exhaustion. This will be an important new frontier for study. This review summarizes published data on the relevant innate and adaptive immune responses to SARS‐CoV‐2. Data characterizing innate and adaptive immune responses have rapidly led to informed therapeutic interventions, including vaccine development and recognition of dysfunctional immune responses that are likely responsible for post‐COVID‐19 autoimmunity. [ABSTRACT FROM AUTHOR]

Summary: The occurrence of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) has been reported since the coronavirus disease 2019 (COVID-19) vaccination, but whether there is a causal relationship or coincidence remains to be verified. We combined the term COVID-19 vaccination with each word of AAV to search for case reports and case series published in PubMed, EMBASE, and Web of Science databases before 13 March 2023. A total of 56 patients who developed AAV after COVID-19 vaccination were identified from 44 research centers. Of the 56 subjects, 43 (76.7%) were vaccinated with the mRNA vaccine, followed by the adenovirus vaccine (14.3%) and inactivated vaccine (9.0%) (P = 0.015). Compared with relapsed AAV, new-onset AAV patients had at least two other diseases previously (P < 0.001). Twenty-five (44.6%) patients presented symptoms after the first injection, and the medium onset time was 12 (1–77) days, while Twenty-eight (50.0%) patients developed symptoms after the second dose, and their medium period was 14 (1–60) days. Forty-four (78.5%) patients achieved remission after immunosuppressive agents, plasma exchange, and hemodialysis. One (1.8%) patient died from progressive respiratory failure and nine (16.1%) did not recover, leaving five patients permanently dependent on hemodialysis. Pathogenic ANCA may be activated by enhanced immune response and epitope spreading after COVID-19 vaccination and induced the occurrence of AAV, especially in genetically susceptible populations. The occurrence of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) has been reported since the coronavirus disease 2019 (COVID-19) vaccination, but whether there is a causal relationship or coincidence remains to be verified. This paper explores the occurrence of AAV, especially in genetically susceptible populations. [ABSTRACT FROM AUTHOR]

Understanding the T-cell response to SARS-CoV-2 is key in patients who lack antibody production. We demonstrate the applicability of a functional assay to measure the T-cell response in a cohort of patients with immunodeficiency. T-cell responses to COVID are now linked to improved outcomes. This paper demonstrates a method to robustly test responses for routine diagnostic use in healthy controls and those unable to make a detectable antibody response due to underlying immune deficiency (primary or acquired). [ABSTRACT FROM AUTHOR]

T cells play key protective but also pathogenic roles in COVID-19. We studied the expression of long non-coding RNAs (lncRNAs) in COVID-19 T-cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highest MALAT1 expression, amongst CD4+ and CD8+ T-cells populations, respectively. We then identified gene signatures that covaried with MALAT1 in single T cells. A significantly higher number of transcripts correlated negatively with MALAT1 than those that correlated. Enriched functional annotations of the MALAT1- anti-correlating gene signature included processes associated with T-cell activation such as cell division, oxidative phosphorylation, and response to cytokine. The MALAT1 anti-correlating gene signature shared by both CD4+ and CD8+ T-cells marked dividing T cells in both the lung and blood of COVID-19 patients. Focussing on the tissue, we used an independent patient cohort of post-mortem COVID-19 lung samples and demonstrated that MALAT1 suppression was indeed a marker of MKI67+ proliferating CD8+ T cells. Our results reveal MALAT1 suppression and its associated gene signature are a hallmark of human proliferating T cells. T cells play important roles in the body's response to COVID-19. We found gene signatures anti-correlating to MALAT1 expression as a marker of proliferating CD4+ Th1 and CD8+ exhausted sub-populations. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a rare side-effect of COVID-19 vaccines. To (a) provide direct advice and reassurance to certain persons with a history of anaphylaxis/complex allergy, in addition to that available in national guidelines, and (b) to provide a medically supervised vaccination, a specialist regional vaccine allergy clinic was established. The main objective was to determine if risk stratification through history can lead to safe COVID-19 vaccination for maximum population coverage. A focused history was taken to establish contraindications to giving COVID-19 vaccines. People who reported a high-risk allergy history were given a vaccine not containing the excipient thought to have directly caused previous anaphylaxis. All vaccines were monitored for 30 min after administration. A total of 206 people were vaccinated between 6 July 2021 and 31 August 2021; Comirnaty (Pfizer-BioNTech) (n = 34), and Janssen (n = 172). In total, 78% were women. Ninety-two people (45%) reported a high-risk allergy history. There were no cases of anaphylaxis. Three people developed urticaria and one of these also developed transient tachycardia. One vaccinee developed a pseudoseizure. Two of 208 people (<1%) referred during this time declined vaccination based on personal preference, despite the assessment of low clinical risk. In our experience, all vaccines with high-risk allergy histories were administered Pfizer BioNTech or Janssen Covid-19 vaccines uneventfully following screening based on allergy-focussed history. Our data support that drug allergy is not associated with a higher risk of vaccine-related anaphylaxis but may act to guide the administration of alternate vaccines to people with polyethylene glycol/polysorbate 80/trometamol allergies or anaphylaxis after the first dose. Individuals with complex allergy histories have experienced COVID-19 vaccine delay and there have been many reports of both immediate and delayed reactions to prior COVID-19 vaccination doses. The study demonstrates a successful strategy for vaccinating the majority of people with documented allergy history, showing those deemed high-risk can be vaccinated safely following screening based on an allergy-focussed history, without need for allergy investigation (e.g. skin prick testing) prior to vaccination. The results of this study act as reassurance of vaccine safety and can be used to guide future community vaccination management of persons reporting drug/food allergy history. [ABSTRACT FROM AUTHOR]

During the last 2 years and a half, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, causing about 6 million deaths. Clinical manifestations are highly variable, ranging from entirely asymptomatic infection to multiorgan failure and death. The outcome in immunocompromised patients is still a matter of debate, and so are the optimal strategies to prevent or treat the infection in these high-risk populations. [ABSTRACT FROM AUTHOR]

Summary: Coronavirus 19 (COVID‐19) has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand the prevalence of autoantibodies associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS‐CoV‐2, suffering from COVID‐19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on the intensive therapy unit (ITU) for non‐COVID reasons. We demonstrate a higher frequency of autoantibodies in the COVID‐19 ITU group compared with non‐COVID‐19 ITU disease control patients and that autoantibodies were also found in the serum 3–5 months post‐COVID‐19 infection. Non‐COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID‐19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies. Our results demonstrate that respiratory viral infection with SARS‐CoV‐2 is associated with the detection of a limited profile of tissue‐specific autoantibodies, detectable using routine clinical immunology assays. Further studies are required to determine whether these autoantibodies are specific to SARS‐CoV‐2 or a phenomenon arising from severe viral infections and to determine the clinical significance of these autoantibodies. [ABSTRACT FROM AUTHOR]

Summary: Background: The impact of countries' bacillus Calmette–Guérin (BCG) vaccination policies on the course of coronavirus disease (COVID‐19) outbreak is a curiosity. In this study, the relationship between BCG vaccination status and severity of COVID‐19 pneumonia and the factors affecting disease severity were investigated. Methods: A retrospective cross‐sectional study was conducted between March and June 2020 in patients diagnosed with COVID‐19 pneumonia, confirmed by severe acute respiratory syndrome coronavirus‐2 polymerase chain reaction positivity in a nasopharyngeal sample and pulmonary infiltrates in computed chest tomography, in a state hospital in Istanbul, Turkey. Socio‐demographic features, body mass index, smoking status, concomitant diseases, income rates and BCG vaccination status of subjects were analyzed. Result: The study population comprised 123 adults with COVID‐19 pneumonia [mean age = 49·7 years, standard deviation = 13·3 years; 82 (66·7%) male]. While the rate of cases vaccinated with BCG is lower (68·5 versus 88·2%, P = 0·026), mean age (54·0 ± 11·5 years versus 38·3 ± 10·7 years; P < 0·001), diabetes (32·6 versus 5·9%, P = 0·002) and low income (84·3 versus 52·9%, P < 0·001) are higher in patients with severe disease compared to those with mild disease. According to multivariate analysis increasing age [odds ratio (OR) = 1·119; 95% confidence interval (CI) = 1·062–1·178, P < 0·001] and low income (OR = 3·209; 95% CI = 1·008–10·222, P = 0·049) are associated with severe disease in COVID‐19 pneumonia. Conclusion: This study reveals that BCG vaccination is not associated with disease severity in COVID‐19 pneumonia. Age and low income are the main determinants of severe COVID‐19 pneumonia. [ABSTRACT FROM AUTHOR]

Summary: Innate immune sensing of viral molecular patterns is essential for development of antiviral responses. Like many viruses, SARS‐CoV‐2 has evolved strategies to circumvent innate immune detection, including low cytosine–phosphate–guanosine (CpG) levels in the genome, glycosylation to shield essential elements including the receptor‐binding domain, RNA shielding and generation of viral proteins that actively impede anti‐viral interferon responses. Together these strategies allow widespread infection and increased viral load. Despite the efforts of immune subversion, SARS‐CoV‐2 infection activates innate immune pathways inducing a robust type I/III interferon response, production of proinflammatory cytokines and recruitment of neutrophils and myeloid cells. This may induce hyperinflammation or, alternatively, effectively recruit adaptive immune responses that help clear the infection and prevent reinfection. The dysregulation of the renin–angiotensin system due to down‐regulation of angiotensin‐converting enzyme 2, the receptor for SARS‐CoV‐2, together with the activation of type I/III interferon response, and inflammasome response converge to promote free radical production and oxidative stress. This exacerbates tissue damage in the respiratory system, but also leads to widespread activation of coagulation pathways leading to thrombosis. Here, we review the current knowledge of the role of the innate immune response following SARS‐CoV‐2 infection, much of which is based on the knowledge from SARS‐CoV and other coronaviruses. Understanding how the virus subverts the initial immune response and how an aberrant innate immune response contributes to the respiratory and vascular damage in COVID‐19 may help to explain factors that contribute to the variety of clinical manifestations and outcome of SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Summary: Since the emergence of COVID‐19, caused by the SARS‐CoV‐2 virus at the end of 2019, there has been an explosion of vaccine development. By 24 September 2020, a staggering number of vaccines (more than 200) had started preclinical development, of which 43 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socializing. Importantly, to effectively control the COVID‐19 pandemic, production needs to be scaled‐up from a small number of preclinical doses to enough filled vials to immunize the world's population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS‐CoV‐2 and the potential for vaccine‐induced immunopathology. We describe the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising preclinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began we are at a point where preclinical and early clinical data are being generated for the vaccines; an overview of this important area will help our understanding of the next phases. [ABSTRACT FROM AUTHOR]