Evidence suggests that immunogenicity to mRNA-based SARS-CoV-2 vaccination in immunosuppressed patients may be reduced. This study assessed the response to 2 doses of mRNA-based SARS-CoV-2 vaccine among 133 participants with underlying chronic inflammatory disease, many of whom were receiving glucocorticoids, B-cell depletion therapy, or other immunosuppressant therapy.

Background: Individuals with Chronic Inflammatory Diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the potency of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management. Methods: We conducted a prospective assessment of mRNA-based vaccine immunogenicity in 133 adults with CIDs and 53 immunocompetent controls. Blood from participants over 18 years of age was collected before initial immunization and 1-2 weeks after the second immunization. Serum anti-SARS-CoV-2 spike (S) IgG+ binding, neutralizing antibody titers, and circulating S-specific plasmablasts were quantified to assess the magnitude and quality of the humoral response following vaccination. Results: Compared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 10-fold reduction in humoral responses, respectively (p<0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analysis (P<0.0001, P=0.0023, respectively). Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization. Conclusions: CID patients treated with immunosuppressive therapies exhibit impaired SARS-CoV-2 vaccine-induced immunity, with glucocorticoids and B cell depletion therapy more severely impeding optimal responses.

Background:Patients with autoimmune disease often require immunosuppressive medications that may increase their risk of developing severe illness from COVID-19. The importance of immunization in this population is particularly high. While the studied vaccines show efficacy in the general population, nothing is known regarding the immune response or safety profile in patients with autoimmune disease and those taking immunomodulatory medications.Objectives:To assess the safety profile and degree of adverse events from SARS-CoV-2 vaccines in patients with autoimmune and inflammatory disease.Methods:This study is part of a larger prospective observational study examining the immunogenicity and safety profile of the SARS-CoV-2 vaccine in patients with immune-mediated diseases taking immunomodulatory medications. Adults with an immune-mediated disease scheduled to receive either a Pfizer or Moderna SARS-COV-2 vaccine were enrolled in this study. Subjects participated in 3 study visits (pre-vaccine, dose 1 (D1) and dose 2 (D2)) where blood, for immunologic assays, and clinical data were collected. Assessments of adverse events (AE), including local and systemic symptoms and validated degree of AE severity were solicited within 7 days of receiving each vaccine dose.Results:To date, 70 patients with autoimmune and inflammatory disease have been enrolled. Demographic and clinical characteristics are shown in Table 1. Distribution of current immunomodulatory medications included prednisone 18.6%, conventional synthetic DMARD 55.7%, targeted synthetic DMARD 4.3%, and biologic DMARD 68.5%. Almost all participants experienced an adverse event following vaccination (D1 96%, D2 100%). Following D1 AEs were generally mild (76.5%) whereas following D2 a large portion of patients experienced AEs that were moderate (47.8%) and severe (30.5%). Injection site pain was the most common AE following both doses followed by arthralgias (D1 21.6%, D2 78.2%), fever (D1 21.6%, D2 70%) and fatigue (D1 21.6%, D2 65.2%) (Figure 1).Figure 1.Solicited Local and Systemic Adverse Events. Percentage of participants who had endorsed an adverse event within 7 days of first or second dose of SARS-CoV-2 Vaccine. ‘Other’ symptoms included chills, blurry vision, brain fog and dizziness.Conclusion:Patients with autoimmune and inflammatory disease experience a significant burden of adverse events following SARS-CoV-2 vaccination with both frequency and severity appearing greater than that of the reported results from the vaccine clinical trials. Several of the endorsed AEs such as fever, fatigue and arthralgias can also be commonly seen in rheumatologic diseases, mimicking flares. While SARS-CoV-2 immunization is crucial in patients with autoimmune diseases, this study demonstrates the importance of understanding the AEs experienced by this patient population to better inform patients of possible expected side effects of SARS-CoV-2 vaccination and further management in the future.Table 1.Demographic and Clinical Characteristics of ParticipantsParameter N (%)N=70Age [years], mean (SD)Age group48.3 ± 16.4 < 6553 (75.7) 65+17 (24.3)Gender Female48 (68.6) Male20 (38.5) Other2 (2.9)Race White47 (67.1) Asian14 (20.0) Hispanic8 (11.4) Black1 (1.4) BMI [kg/m2], mean (SD)25.0 ± 5.4Immunologic Diagnosis Rheumatoid Arthritis21 (30.0) Spondyloarthritis*21 (30.0) Systemic Lupus Erythematous8 (11.4) Connective Tissue Disease, Other‡12 (17.1) Vasculitis3 (4.2) Inflammatory Bowel Disease7 (10.0) Autoinflammatory Syndrome5 (7.1) Multiple Sclerosis2 (2.9) IgG4 Related Disease2 (2.9)Disease Duration [years], mean (SD)9.0 ± 5Medications Prednisone13 (18.6)DMARDs Hydroxychloroquine16 (22.9) Methotrexate15 (21.4) Sulfasalazine6 (8.6) Tofacitinib3 (4.3) Azathioprine2 (2.9)Biologics TNF inhibitor33 (47.1) Rituximab7 (10) Abatacept6 (8.6) IL-23 inhibitor2 (2.9)* Spondyloarthritis includes Axial Spondyloarthritis and Psoriatic Arthritis. ‡ Other Connective Tissue Disease includes scleroderma, Sjogren’s syndrome, polymyositis, and UCTD.Disclosure of Interests:Monica Yang: None declared, Patti Katz: None declared, Diana Paez: None declared, Alexander Carvidi: None declared, Mehrdad Matloubian: None declared, Mary Nakamura: None declared, Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, Gilead, GSK, and Novartis, Grant/research support from: Pfizer and UCB

The current SARS-CoV-2 pandemic is a historical event that has come to change the way of life for humanity; where the population is the main subject of cause and solution. Considering the global variation of propagation, each country has taken different positions, decisions and resources where the time for making different decisions has also been an important factor. In Mexico, the SARS CoV-2 situation has been confronted mainly with government decisions and the actions of the population. The successes or failures have impacted various dimensions of society in each of the states that make up the country. In this research, some impacted life dimensions are analyzed: Social, mental, educational, economic and environmental. It is possible to say that the impact of the pandemic were influenced, among other aspects; by the state of health and nutrition associated with the lifestyle in which the population was at the arrival of the pandemic. This impact is also influenced by commercial activities, which are linked to the economic mobility of those who buy and those who sell. Also, other aspects that have influenced the impact of this pandemic; it is possible to highlight the lack of culture on the part of the population in the use of face masks and the non-obligatory use of it by the leaders. This, added to various other factors, have had a great impact on the number of infected cases and deaths in the country; primarily in Mexico City and the State of Mexico. It is worth mentioning that, despite the negative impact due to the pandemic, there are also positive aspects. Finally, it is possible to say that it is necessary for the population to develop more awareness. The population has a definitive role in containing the pandemic and to incorporate the new changes, in its life in order to precisely preserve.

Objective. Little is known regarding the reactogenicity and related SARS-CoV-2 vaccine response in patients with chronic inflammatory disease (CID). Our objective was to characterize the adverse event profile of CID patients following SARS-CoV-2 vaccination and understand the relationship between reactogenicity and immunogenicity of SARS-CoV-2 vaccines.Methods. CID patients and healthy controls eligible to receive messenger RNA (mRNA) SARS-CoV-2 vaccines participated in 3 study visits (pre-vaccine, after dose 1, and after dose 2) in which blood and clinical data were collected. Assessment of adverse events were solicited within 7 days of receiving each dose. Serum anti-SARS-CoV-2 spike IgG ± antibody titers were quantified following vaccination. Statistical analysis was performed utilizing mixed models and tobit regressions, with adjustment for covariates.Results. The present study included 441 participants (322 CID patients and 119 control subjects). Compared to controls, CID patients reported greater symptom severity after dose 1 (P = 0.0001), including more myalgia and fatigue (P < 0.05). For immunogenicity, a higher symptom severity after dose 1 and a higher number of symptoms after dose 2 was associated with higher antibody titers (P ≤ 0.05). Each increase of 1 symptom was associated with a 15.1% increase in antibody titer. Symptom association was strongest with site pain after dose 1 (105%; P = 0.03) and fatigue after dose 2 (113%; P = 0.004).Conclusion. Patients with CID have a distinct reactogenicity profile following SARS-CoV-2 vaccination compared to controls. Furthermore, there is an association between increased reactogenicity and increased vaccine response. This finding may speak to the more variable immunogenicity in CID patients and may be an important indicator of vaccine response to the novel SARS-CoV-2 vaccines.