Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals. (preprint)

Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

Sufficient reproduction numbers to prevent recurrent epidemics (preprint)

Current practice in the design and evaluation of epidemic control measures, including vaccination, is largely based on reproduction numbers (RNs), which represent prognostic indexes of long-term disease transmission, both in naive populations (basic RN) and in the presence of prior exposure or interventions (effective RN). A standard control objective is to establish herd immunity, e.g., by immunizing enough susceptible individuals to achieve RN<1. However, attaining this goal is not sufficient to avoid transient outbreaks that, in the short term, might revamp epidemics by coalescence of subthreshold flare-ups. Using reactivity analysis applied to a discrete SIR model with age-of-infection structure, we determine sufficient conditions to prevent transient epidemic dynamics and recurrent, non-periodic outbreaks due to imported cases. These conditions are based on fundamental infection characteristics, namely the average infectiousness clearance rate, the generation time distribution, and the RN. We show that preventing subthreshold epidemicity requires stricter RN thresholds than simply maintaining RN<1. Taking into account a wide spectrum of respiratory viral infections, epidemicity-curbing RN thresholds vary between 0.10 (rubella) and 0.51 (MERS), with a median of 0.26 close to the estimate of 0.24 for the ancestral SARS-CoV-2 virus. The portion of the population that needs to be included in containment efforts to avoid short-term outbreaks is considerably higher than herd immunity thresholds (HITs) based solely on the basic RN (e.g., 93% vs. 72% for ancestral SARS-CoV-2). We also find that subthreshold epidemicity is harder to prevent for pathogens with a longer mean generation time, smaller standard deviation of the generation time distribution, longer duration of infection, and higher RN. Determining sufficient RN thresholds to prevent transient outbreaks is a key challenge in disease ecology, with practical consequences for the design of control measures, as the weaker RN reductions and HITs associated with customary control targets may prove ineffective in preventing potentially recurrent flare-ups. Due to its modest data requirements, our modeling framework may also have important implications for human and non-human diseases caused by emerging pathogens.

Shared genetic architecture and causal relationship between the age at first sex and COVID-19: A large-scale cross-trait analysis (preprint)

COVID-19 is genetically associated with numerous immune disorders, and young age at first intercourse (AFS) may lead to early activation of innate immunity. However, the genetic overlap between COVID-19 and AFS remains undetermined. Here we perform a large-scale cross-trait analysis to investigate their shared genetic etiology and causal relationship. An overall negative genetic correlation between the AFS and three COVID-19 traits was observed. We further identified 186, 221, and 213 shared genetic loci for AFS-COVID-19 infection, hospitalization, and severity, respectively. Among these shared loci, those closest to the genes CADM2, and ARPC1B showed the strongest signals. Our post-GWAS functional analysis revealed that the shared mapped genes were mainly involved in neural genesis and development within several brain structures. Finally, bidirectional Mendelian randomization (MR) results showed that earlier sexual debut may increase the risk of SARS-CoV-2 infection, hospitalization, and severity.

SARS-CoV-2 infection elucidates unique features of pregnancy-specific immunity (preprint)

Pregnancy is a risk factor for increased severity of SARS-CoV-2 and other respiratory infections. The mechanisms underlying this risk have not been well-established, partly due to a limited understanding of how pregnancy shapes immune responses. To gain insight into the role of pregnancy in modulating immune responses at steady state and upon perturbation, we collected peripheral blood mononuclear cells (PBMC), plasma, and stool from 226 women, including 152 pregnant individuals (n = 96 with SARS-CoV-2 infection and n = 56 healthy controls) and 74 non-pregnant women (n = 55 with SARS-CoV-2 and n = 19 healthy controls). We found that SARS-CoV-2 infection was associated with altered T cell responses in pregnant compared to non-pregnant women. Differences included a lower percentage of memory T cells, a distinct clonal expansion of CD4-expressing CD8+ T cells, and the enhanced expression of T cell exhaustion markers, such as programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain-3 (Tim-3), in pregnant women. We identified additional evidence of immune dysfunction in severely and critically ill pregnant women, including a lack of expected elevation in regulatory T cell (Treg) levels, diminished interferon responses, and profound suppression of monocyte function. Consistent with earlier data, we found maternal obesity was also associated with altered immune responses to SARS-CoV-2 infection, including enhanced production of inflammatory cytokines by T cells. Certain gut bacterial species were altered in pregnancy and upon SARS-CoV-2 infection in pregnant individuals compared to non-pregnant women. Shifts in cytokine and chemokine levels were also identified in the sera of pregnant individuals, most notably a robust increase of interleukin-27 (IL-27), a cytokine known to drive T cell exhaustion, in the pregnant uninfected control group compared to all non-pregnant groups. IL-27 levels were also significantly higher in uninfected pregnant controls compared to pregnant SARS-CoV-2-infected individuals. Using two different preclinical mouse models of inflammation-induced fetal demise and respiratory influenza viral infection, we found that enhanced IL-27 protects developing fetuses from maternal inflammation but renders adult female mice vulnerable to viral infection. These combined findings from human and murine studies reveal nuanced pregnancy-associated immune responses, suggesting mechanisms underlying the increased susceptibility of pregnant individuals to viral respiratory infections.

The number of similar epitopes determines the longevity of immunological memory (preprint)

The half-life of specific antibodies against various antigens varies tremendously from a few months to over 10,000 years. The reasons are largely unknown. Through epitope analysis of representative viruses, we found that the longevity of immunological memory may be correlated with the number of epitopes with similar sequences (EWSS) within each virus. Accordingly, a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with 4.5-times higher antibody titers and over 100 months of half-life was developed in a rabbit model. The decay pattern of antibodies against each epitope or the entire SARS-CoV-2 spike protein was roughly correlated with the number of EWSS in immunizationtreatments, –that is, for every additional EWSS, the half-life of the antibody would be doubled. After immunization, proportions of antigen-specific memory B cells (MBC) first increased and then decreased. In the descending phase, the antibody titers were positively correlated with the numbers of MBC. This study also discusses improvement measures for vaccines against other viruses.

Determinants of COVID-19 Disease Severity-Lessons from Primary and Secondary Immune Disorders including Cancer.

At the beginning of the COVID-19 pandemic, patients with primary and secondary immune disorders-including patients suffering from cancer-were generally regarded as a high-risk population in terms of COVID-19 disease severity and mortality. By now, scientific evidence indicates that there is substantial heterogeneity regarding the vulnerability towards COVID-19 in patients with immune disorders. In this review, we aimed to summarize the current knowledge about the effect of coexistent immune disorders on COVID-19 disease severity and vaccination response. In this context, we also regarded cancer as a secondary immune disorder. While patients with hematological malignancies displayed lower seroconversion rates after vaccination in some studies, a majority of cancer patients' risk factors for severe COVID-19 disease were either inherent (such as metastatic or progressive disease) or comparable to the general population (age, male gender and comorbidities such as kidney or liver disease). A deeper understanding is needed to better define patient subgroups at a higher risk for severe COVID-19 disease courses. At the same time, immune disorders as functional disease models offer further insights into the role of specific immune cells and cytokines when orchestrating the immune response towards SARS-CoV-2 infection. Longitudinal serological studies are urgently needed to determine the extent and the duration of SARS-CoV-2 immunity in the general population, as well as immune-compromised and oncological patients.

Roles of Infection in Psoriasis.

Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations. Genetic predisposition, environmental factors, and immune dysfunction all contribute to the pathogenesis of psoriasis with host-microbe interaction governing the progression of this disease. Emerging evidence has indicated that infection is an environmental trigger for psoriasis and plays multiple roles in its maintenance as evidenced by the frequent association between guttate psoriasis onset and acute streptococcal infection. Different infectious factors act on immune cells to produce inflammatory cytokines that can induce or aggravate psoriasis. In addition to bacterial infections, viral and fungal infections have also been shown to be strongly associated with the onset or exacerbation of psoriasis. Intervention of skin microbiota to treat psoriasis has become a hot research topic. In this review, we summarize the effects of different infectious factors (bacteria, viruses, and fungi) on psoriasis, thereby providing insights into the manipulation of pathogens to allow for the identification of improved therapeutic options for the treatment of this condition.

Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee.

We report the updated classification of inborn errors of immunity, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 55 novel monogenic gene defects, and 1 phenocopy due to autoantibodies, that have either been discovered since the previous update (published January 2020) or were characterized earlier but have since been confirmed or expanded in subsequent studies. While variants in additional genes associated with immune diseases have been reported in the literature, this update includes only those that the committee assessed that reached the necessary threshold to represent novel inborn errors of immunity. There are now a total of 485 inborn errors of immunity. These advances in discovering the genetic causes of human immune diseases continue to significantly further our understanding of molecular, cellular, and immunological mechanisms of disease pathogenesis, thereby simultaneously enhancing immunological knowledge and improving patient diagnosis and management. This report is designed to serve as a resource for immunologists and geneticists pursuing the molecular diagnosis of individuals with heritable immunological disorders and for the scientific dissection of cellular and molecular mechanisms underlying monogenic and related human immune diseases.

Emotional, hyperactivity and inattention problems in adolescents with immunocompromising chronic diseases during the COVID-19 pandemic.

OBJECTIVE: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. METHODS: A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). RESULTS: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00‒7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08‒3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12‒4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93‒0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95‒0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16‒0.77; p = 0.026) remained inversely associated with abnormal HI scores. CONCLUSION: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.

The Epidemiological Pattern of Seasonal Influenza in Four Sentinel Sites in Iraq (preprint)

ABSTRACT Introduction: Influenza is an acute viral infection with significant morbidity and mortality. Its occur annually each winter is called seasonal influenza and is preventable through safe vaccine. Aim: To know the epidemiological pattern of patients with seasonal influenza in Iraqi sentinel sites. Methods: A cross- sectional study carried out on records of patients who attended four sentinel sites and registered to have influenza-like illness (ILI) or severe acute respiratory infection (SARI), and laboratory investigated. Results: The total number of cases was 1124, 36.2% of them aged 19-39 years; 53.9% were female; 74.9% lived in urban areas; 64.3% diagnosed as ILI and 35.7% as SARI. 15.9% had diabetes, 12.7% had heart disease, 4.8% had asthma, 3% had a chronic lung disease, and 2% had hematological disease. 94.6% did not get influenza vaccine. About COVID-19 vaccine, 69.4% did not vaccinated, 3.5% get only 1 dose, and 27.1% completed 2 doses. Only the SARI cases needed admission, among them 95.7% were cured. 6.5% were diagnosed as influenza- A virus, 26.1% had COVID-19, and 67.5% were negative. Among those with influenza, 97.3% had H3N2 subtype, and 2.7% had H1N1 pdm09. Conclusions: The percentage of influenza virus in Iraq is relatively small. The age, classification of case (ILI or SARI), having diabetes, heart disease, or immunological disease, and taking COVID-19 vaccine have a significant association with influenza. Recommendations: It’s needed for similar sentinel sites in other health directorates and for rising health education about seasonal influenza and its vaccine.

Optimising the yield from bronchoalveolar lavage on human participants in infectious disease immunology research (preprint)

Bronchoalveolar lavage (BAL) is becoming a common procedure for research into infectious disease immunology. Little is known about the clinical factors which influence the main outcomes of the procedure. In research participants who underwent BAL according to guidelines, the BAL volume yield, and cell yield, concentration, viability, pellet colour and differential count were analysed for association with important participant characteristics such as active tuberculosis (TB) disease, TB exposure, HIV infection and recent SARS-CoV-2 infection. In 337 participants, BAL volume and BAL cell count were correlated in those with active TB disease, and current smokers. The right middle lobe yielded the highest volume. BAL cell and volume yields were lower in older participants, who also had more neutrophils. Current smokers yielded lower volumes and higher numbers of all cell types, and usually had a black pellet. Active TB disease was associated with higher cell yields, and higher proportions of granulocytes, but this declined at the end of treatment. HIV infection was associated with lower cell yields and more bloody pellets, and recent SARS-CoV-2 infection with a higher proportion of lymphocytes. These results allow researchers to optimise their participant and end assay selection for projects involving lung immune cells.

Recruitment of plasma cells to the bone marrow in primary and secondary immune reactions (preprint)

Bone marrow plasma cells (BMPC) emerge as a consequence of immune reactions and are considered the source of antibodies that protect against recurrent infectious diseases throughout life. Despite their importance, it remains unclear if these cells reflect different activation environments or the differentiation/maturation stages of their precursors. Here we track the recruitment of plasma cells, generated in primary and secondary immune reactions to SARS-CoV-2 spike protein vaccines, to the human bone marrow. Trajectories based on single cell transcriptomes and antigen-receptor clonotypes of antibody-secreting cells exiting the immune reaction and of those residing in the bone marrow, allow to follow the evolution of the immune response to these vaccines, leading to sequential colonization of these cells to different compartments (clans) of BMPC, and their establishment as long-lived (memory) plasma cells. In primary immune reactions, both CD19low (clans 1 and 4) and CD19high (clan 0) BMPC are generated. In secondary immune reactions, mostly CD19high BMPC of the largest compartment (clan 0) are generated, resulting from the reactivation of memory B lymphocytes. The latter is also observed in vaccinated convalescent individuals and upon recall vaccination against diphtheria/tetanus/pertussis (DTP). Thus, humoral immunological memory, i.e. serum antibodies secreted by long-lived memory BMPC, is generated already in the primary immune response, more so in the secondary, and it represents the evolution of the immune response.

EAACI statement on the pathogenesis, immunology, and immune-targeted management of the Multisystem Inflammatory Syndrome in Children (MIS-C) or Pediatric Inflammatory Multisystem Syndrome (PIMS). (preprint)

Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). It develops approximately four weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS-C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS-C, diagnosis, treatment, follow-up, and the role of COVID-19 vaccinations. MIS-C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short-term outcome, MIS-C patients should be followed-up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID-19 vaccination is a safe and effective measure to prevent MIS-C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS-C developed by the Immunology Section of the EAACI.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Syndrome: A Common Neuroimmune Ground? (preprint)

A Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology under growing interest now in view of the increasingly recognized post-COVID syndrome as a new entity with similar clinical presentation. We performed the first cross-sectional study of ME/CFS in community population in Russia and then described and compared some clinical and pathophysiological characteristics of ME/CFS and post-COVID syndrome as neuroimmune disorders. Of the cohort of 76 individuals who suggested themselves suffering from ME/CFS 56 subsequently were confirmed as having CFS/ME according to ≥1 of the 4 most commonly used case definition. Of the cohort of 14 individuals with post-COVID-19 syndrome 14 met diagnostic criteria for ME/CFS. The prevalence of clinically expressed and subclinical anxiety and depression in ME / CFS and post-COVID ME/CFS did not differ significantly from that in healthy individuals. Severity of anxiety / depressive symptoms did not correlate with the severity of fatigue neigther in ME / CFS nor in post-COVID ME/CFS, but the positive correlation was found between the severity of fatigue and 20 other symptoms of ME / CFS related to the domains of “post-exertional exhaustion”, “immune dysfunction”, “sleep disturbances”, "dysfunction of the autonomic nervous system", "neurological sensory / motor disorders" and "pain syndromes". Immunological abnormalities were identified in 12/12 patients with ME / CFS according to the results of laboratory testing. The prevalence of postural orthostatic tachycardia assessed by the active standing test was 37.5% in ME / CFS and 75.0% in post-COVID ME/CFS (the latter was higher than in healthy controls, p = 0.02) There was a more pronounced increase in heart rate starting from the 6th minute of the test in post-COVID ME/CFS compared with the control group. Assessment of the functional characteristics of microcirculation by laser doppler flowmetry revealed obvious and very similar changes in ME/CFS and post-COVID ME/CFS compared to the healthy controls. The identified pattern corresponded to the hyperemic form of microcirculation disorders, usually observed in acute inflammatory processes or in deficiency of systemic vasoconstriction influences.

Immunomodulatory Mechanisms of Mesenchymal Stem Cells and Their Potential Clinical Applications.

Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity of self-renewal, homing, and low immunogenicity. These distinct biological characteristics have already shown immense potential in regenerative medicine. MSCs also possess immunomodulatory properties that can maintain immune homeostasis when the immune response is over-activated or under-activated. The secretome of MSCs consists of cytokines, chemokines, signaling molecules, and growth factors, which effectively contribute to the regulation of immune and inflammatory responses. The immunomodulatory effects of MSCs can also be achieved through direct cell contact with microenvironmental factors and immune cells. Furthermore, preconditioned and engineered MSCs can specifically improve the immunomodulation effects in diverse clinical applications. These multifunctional properties of MSCs enable them to be used as a prospective therapeutic strategy to treat immune disorders, including autoimmune diseases and incurable inflammatory diseases. Here we review the recent exploration of immunomodulatory mechanisms of MSCs and briefly discuss the promotion of the genetically engineered MSCs. Additionally, we review the potential clinical applications of MSC-mediated immunomodulation in four types of immune diseases, including systemic lupus erythematosus, Crohn's disease, graft-versus-host disease, and COVID-19.

Severe fatigue as symptom of long COVID is characterized by increased expression of inflammatory genes in monocytes, increased serum pro-inflammatory cytokines, and increased CD8+ T-lymphocytes. A putative dysregulation of the immune-brain axis, the coagulation process, and auto-inflammation to explain the diversity of long COVID symptoms (preprint)

Background. A significant proportion of patients with SARS-CoV-2 infection develops long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immunologic profiling of fatigued and non-fatigued long COVID patients and age and gender matched healthy controls (HCs). Methods. We included 37 long COVID patients with and 36 without severe fatigue and assessed inflammation-related monocyte gene expression, serum levels of inflammatory cytokines, and leukocyte and lymphocyte subsets 3-6 months after hospital discharge, and followed clinical symptoms up to one year. Results. Long COVID with fatigue represented a severe variant with many symptoms (median 9 [IQR 5.0-10.0] symptoms) and signs of cognitive failure (41%) and depression (>24%). Symptoms persisted up to one year follow-up. Fatigued patients showed increased expression of inflammatory genes in monocytes, increased serum IL-6, TNF-, galectin-9, and CXCL10, and increased CD8+ T-lymphocytes compared to HCs. Non-fatigued long COVID patients were arbitrarily divided in those with moderately severe disease (4 [2.5-5.0] symptoms, primarily impaired fitness, n=25) and those with mild disease (1 [1.0-2.0] symptom, n=11). Symptoms in non-fatigued long COVID patients persisted up to one year follow-up. Moderately severe patients showed reduced CD45RO- naive CD4+ T-lymphocytes and CD25+FOXP3+ regulatory CD4+ T-lymphocytes and limited monocyte and serum (galectin-9) inflammation. Mild patients showed monocyte and serum (IL-6, galectin-9) inflammation and decreased CD4+ T-lymphocyte subsets (T-helper 1 cells). Conclusion. Long COVID with fatigue is associated with many concurrent and persistent symptoms up to one year after hospitalization and with clear signs of low grade inflammation and increased CD8+ T-lymphocytes. We showed that long COVID is a clinical and immunologic heterogeneous disorder. Diagnostic tools and personalized therapies combatting the diverse immune abnormalities might be required to alleviate the persisting disabling complaints of the patients.

Autoimmune and autoinflammatory conditions after COVID-19 vaccination. New case reports and updated literature review.

Autoimmunity linked to COVID-19 immunization has been recorded throughout the pandemic. Herein we present six new patients who experienced relapses of previous autoimmune disease (AD) or developed a new autoimmune or autoinflammatory condition following vaccination. In addition, we documented additional cases through a systematic review of the literature up to August 1st, 2022, in which 464 studies (928 cases) were included. The majority of patients (53.6%) were women, with a median age of 48 years (IQR: 34 to 66). The median period between immunization and the start of symptoms was eight days (IQR: 3 to 14). New-onset conditions were observed in 81.5% (n: 756) of the cases. The most common diseases associated with new-onset events following vaccination were immune thrombocytopenia, myocarditis, and Guillain-Barré syndrome. In contrast, immune thrombocytopenia, psoriasis, IgA nephropathy, and systemic lupus erythematosus were the most common illnesses associated with relapsing episodes (18.5%, n: 172). The first dosage was linked with new-onset events (69.8% vs. 59.3%, P = 0.0100), whereas the second dose was related to relapsing disease (29.5% vs. 59.3%, P = 0.0159). New-onset conditions and relapsing diseases were more common in women (51.5% and 62.9%, respectively; P = 0.0081). The groups were evenly balanced in age. No deaths were recorded after the disease relapsed, while 4.7% of patients with new-onset conditions died (P = 0.0013). In conclusion, there may be an association between COVID-19 vaccination and autoimmune and inflammatory diseases. Some ADs seem to be more common than others. Vaccines and SARS-CoV-2 may induce autoimmunity through similar mechanisms. Large, well-controlled studies are warranted to validate this relationship and assess additional variables such as genetic and other environmental factors.

Rates of COVID-19-Associated Hospitalization in Immunocompromised Individuals in Omicron-era: A Population-Based Observational Study Using Surveillance Data in British Columbia, Canada (preprint)

Background: People with immune dysfunction have a higher risk for severe COVID-19 outcomes. Omicron variant is associated with a lower rate of hospitalization but higher vaccine escape. This population-based study quantifies COVID-19 hospitalization rate in the Omicron-dominant era among vaccinated people with immune dysfunction, identified as clinically extremely vulnerable (CEV) population before COVID-19 treatment was widely offered. Methods: All COVID-19 cases were reported to the British Columbia Centre for Disease Control (BCCDC) between January 7, 2022 and March 14, 2022. Case and population hospitalization rates were estimated across CEV status, age groups and vaccination status. Cumulative rates of hospitalizations for the study period were also compared between CEV and non-CEV individuals matched by sex, age group, region, and vaccination characteristics. Findings: A total of 5,591 COVID-19 reported cases and 1,153 hospitalizations among CEV individuals were included. A third vaccine dose with mRNA vaccine offered additional protection against severe illness in CEV individuals. Vaccinated CEV population still had a significantly higher breakthrough hospitalization rate compared with non-CEV individuals. Interpretation: CEV population remains a higher risk group and may benefit from additional booster doses and pharmacotherapy. Funding: BC Centre for Disease Control and Provincial Health Services Authority