Impaired immunogenicity to COVID-19 vaccines in autoimmune systemic diseases. High prevalence of non-response in different patients’ subgroups

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53–1203) vs 825 (451–1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals

POS1246 COVID-19 IN ITALIAN PATIENTS WITH RHEUMATIC AUTOIMMUNE SYSTEMIC DISEASES: RESULTS OF A NATIONWIDE SURVEY STUDY

Background: SARS-CoV-2 infection poses a serious challenge for patients with rheumatic autoimmune systemic diseases (ASD), characterized by marked immune-system dysregulation and frequent visceral organ involvement. Objectives: To evaluate the impact of Covid-19 pandemic in a large series of Italian patients with ASD. Methods: Our multicenter telephone survey (8-week period, March-April 2020) included a large series of 2,994 patients (584 M, 2,410 F, mean age 58.9±13.4SD years) with ASD followed at 34 tertiary referral centers of 14 regions of northern, central, and southern Italian macro areas, characterized by different prevalence of SARS-CoV-2 infection. According to currently used criteria, Covid-19 was classified as definite Covid-19 (signs or symptoms of Covid-19 confirmed by positive oral/nasopharyngeal swabs at PCR testing) or highly suspected Covid-19 (signs or symptoms highly

COVID-19 and systemic sclerosis: clinicopathological implications from Italian nationwide survey study

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COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity

Purpose: Mixed cryoglobulinemia syndrome (MCs) is a rare immunoproliferative systemic disorder with cutaneous and multiple organ involvement. Our multicenter survey study aimed to investigate the prevalence and outcome of COVID-19 and the safety and immunogenicity of COVID-19 vaccines in a large MCs series. Methods: The survey included 430 unselected MCs patients (130 M, 300 F; mean age 70 ± 10.96 years) consecutively collected at 11 Italian referral centers. Disease classification, clinico-serological assessment, COVID-19 tests, and vaccination immunogenicity were carried out according to current methodologies. Results: A significantly higher prevalence of COVID-19 was found in MCs patients compared to Italian general population (11.9% vs 8.0%, p < 0.005), and the use of immunomodulators was associated to a higher risk to get infected (p = 0.0166). Moreover, higher mortality rate was recorded in MCs with COVID-19 compared to those without (p < 0.01). Patients’ older age (≥ 60 years) correlated with worse COVID-19 outcomes. The 87% of patients underwent vaccination and 50% a booster dose. Of note, vaccine-related disease flares/worsening were significantly less frequent than those associated to COVID-19 (p = 0.0012). Impaired vaccination immunogenicity was observed in MCs patients compared to controls either after the first vaccination (p = 0.0039) and also after the booster dose (p = 0.05). Finally, some immunomodulators, namely, rituximab and glucocorticoids, hampered the vaccine-induced immunogenicity (p = 0.029). Conclusions: The present survey revealed an increased prevalence and morbidity of COVID-19 in MCs patients, as well an impaired immunogenicity even after booster vaccination with high rate of no response. Therefore, MCs can be included among frail populations at high risk of infection and severe COVID-19 manifestations, suggesting the need of a close monitoring and specific preventive/therapeutical measures during the ongoing pandemic

Absent or suboptimal response to booster dose of COVID-19 vaccine in patients with autoimmune systemic diseases

Autoimmune systemic diseases (ASD) show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed at evaluating the seroconversion elicited by COVID-19 vaccine over the entire vaccination cycle including the booster dose. Among 478 unselected ASD patients originally evaluated at the end of the first vaccination cycle (time 1), 344 individuals were re-evaluated after a 6-month period (time 2), and 244 after the booster vaccine dose (time 3). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was assessed by measuring serum IgG-neutralizing antibody (NAb) on samples obtained at the three time points in both patients and 502 age-matched controls. In the 244 ASD group that received booster vaccine and monitored over the entire follow-up, the mean serum NAb levels (time 1, 2, and 3: 696.8 ± 52.68, 370.8 ± 41.92, and 1527 ± 74.16SD BAU/mL, respectively; p &lt; 0.0001) were constantly lower compared to controls (p &lt; 0.0001), but they significantly increased after the booster dose compared to the first two measurements (p &lt; 0.0001). The percentage of patients with absent/suboptimal response to vaccine significantly decreased after the booster dose compared to the first and second evaluations (time 1, 2, and 3: from 28.2% to 46.3%, and to 7.8%, respectively; p &lt; 0.0001). Of note, the percentage of patients with absent/suboptimal response after the booster dose was significantly higher compared to controls (19/244, 7.8% vs 1/502, 0.2%; p &lt; 0.0001). Similarly, treatment with immune-modifiers increased the percentage of patients exhibiting absent/suboptimal response (16/122, 13.1% vs 3/122, 2.46%; p = 0.0031). Overall, the above findings indicate the usefulness of booster vaccine administration in ASD patients. Moreover, the persistence of a significantly higher percentage of individuals without effective seroconversion (7.8%), even after the booster dose, warrants for careful monitoring of NAb levels in all ASD patients to identify those with increased risk of infection. In this particularly frail patients' setting, tailored vaccination and/or therapeutic strategy are highly advisable

Impaired immunogenicity to COVID-19 vaccines in autoimmune systemic diseases. High prevalence of non-response in different patients’ subgroups

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53–1203) vs 825 (451–1542) BAU/mL, p &lt; 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p &lt; 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p &lt; 0.0001), or rituximab (p &lt; 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals

COVID-19 and systemic sclerosis: clinicopathological implications from Italian nationwide survey study

none70nononeFerri C.; Giuggioli D.; Raimondo V.; Dagna L.; Riccieri V.; Zanatta E.; Guiducci S.; Tavoni A.; Foti R.; Cuomo G.; De Angelis R.; Cozzi F.; Murdaca G.; Cavazzana I.; Romeo N.; Codullo V.; Ingegnoli F.; Pellegrini R.; Varcasia G.; Rossa A.D.; De Santis M.; Abignano G.; Colaci M.; Caminiti M.; L'Andolina M.; Lubrano E.; Spinella A.; Lumetti F.; De Luca G.; Bellando-Randone S.; Visalli E.; Bilia S.; Giannini D.; Masini F.; Pellegrino G.; Pigatto E.; Generali E.; Dall'Ara F.; Mariano G.P.; Barsotti S.; Pettiti G.; Zanframundo G.; Brittelli R.; Aiello V.; Scorpiniti D.; Ferrari T.; Caminiti R.; Campochiaro C.; D'Angelo S.; Iannone F.; Matucci-Cerinic M.; Doria A.; Miccoli M.; Fallahi P.; Antonelli A.; Della Rossa A.; Pagano Mariano G.; Cecchetti R.; Gigliotti P.; Olivo D.; Ursini F.; Brusi V.; Meliconi R.; Scarpa R.; Fusaro E.; Zignego A.L.; Paparo S.R.; Ragusa F.; Elia G.; Ferrari S.M.Ferri, C.; Giuggioli, D.; Raimondo, V.; Dagna, L.; Riccieri, V.; Zanatta, E.; Guiducci, S.; Tavoni, A.; Foti, R.; Cuomo, G.; De Angelis, R.; Cozzi, F.; Murdaca, G.; Cavazzana, I.; Romeo, N.; Codullo, V.; Ingegnoli, F.; Pellegrini, R.; Varcasia, G.; Rossa, A. D.; De Santis, M.; Abignano, G.; Colaci, M.; Caminiti, M.; L'Andolina, M.; Lubrano, E.; Spinella, A.; Lumetti, F.; De Luca, G.; Bellando-Randone, S.; Visalli, E.; Bilia, S.; Giannini, D.; Masini, F.; Pellegrino, G.; Pigatto, E.; Generali, E.; Dall'Ara, F.; Mariano, G. P.; Barsotti, S.; Pettiti, G.; Zanframundo, G.; Brittelli, R.; Aiello, V.; Scorpiniti, D.; Ferrari, T.; Caminiti, R.; Campochiaro, C.; D'Angelo, S.; Iannone, F.; Matucci-Cerinic, M.; Doria, A.; Miccoli, M.; Fallahi, P.; Antonelli, A.; Della Rossa, A.; Pagano Mariano, G.; Cecchetti, R.; Gigliotti, P.; Olivo, D.; Ursini, F.; Brusi, V.; Meliconi, R.; Scarpa, R.; Fusaro, E.; Zignego, A. L.; Paparo, S. R.; Ragusa, F.; Elia, G.; Ferrari, S. M

Impact of COVID-19 and vaccination campaign on 1,755 systemic sclerosis patients during first three years of pandemic. Possible risks for individuals with impaired immunoreactivity to vaccine, ongoing immunomodulating treatments, and disease-related lung involvement during the next pandemic phase

Introduction: The impact of COVID-19 pandemic represents a serious challenge for 'frail' patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic. Patients and method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines. Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evaluated by comparing the COVID-19-related death rate recorded during pre- and post-vaccination pandemic periods, revealed a quite stable outcome in SSc patients (death rate from 2.54 % to 1.76 %; p = ns), despite the significant drop of mortality observed in the Italian general population (from 2.95 % to 0.29 %; p < 0.0001). Conclusions: An increased COVID-19 prevalence and mortality rate was recorded in SSc patients; moreover, the efficacy of vaccines in term of improved outcomes was less evident in SSc compared to Italian general population. This discrepancy might be explained by concomitant adverse prognostic factors: increased rate of non-responders to vaccine in SSc series, low percentage of individuals with four or more doses of vaccine, ongoing immunomodulating treatments, disease-related interstitial lung disease, and/or reduced preventive measures in the second half of pandemic. A careful monitoring of response to COVID-19 vaccines together with adequate preventive/therapeutical strategies are highly recommendable in the near course of pandemic in this frail patients' population

Covid-19 And Rheumatic Autoimmune Systemic Diseases: Role of Pre-Existing Lung Involvement and Ongoing Treatments

85noAbstract Background: The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations. Objective: To investigate the prevalence of symptomatic Covid-19 and its correlations with both organ involvement and ongoing treatments in a large series of Italian ASD patients during the first wave of pandemic. Method: Our multicenter telephone 6-week survey included 3,029 unselected ASD patients enrolled at 36 tertiary referral centers of northern, central, and southern Italian macro-areas with different diffusion of pandemic. Symptomatic SARS-CoV-2 infection was classified as definite Covid-19 (presence of symptoms plus positive oral/nasopharyngeal swabs) or highly suspected Covid-19 (highly suggestive symptoms, in absence of a swab testing). Results: A significantly higher prevalence of definite plus highly suspected Covid-19 compared to Italian general population was detected in the whole ASD series (p=.000), as well as in patients from the three macro-areas (p=.000 in all). Statistically higher prevalence of Covid-19 was also found in connective tissue diseases compared to chronic arthritis subgroup (p=.000) and in ASD patients with pre-existing interstitial lung involvement (p=.000). Patients treated with either conventional disease modifying anti-rheumatic drugs (DMARDs) and/or biological DMARDs showed a significantly lower prevalence of Covid-19 (p=.000 in both). Finally, scleroderma patients undergoing low-dose aspirin showed significantly lower rate of Covid-19 compared to those without (p=0.003). Conclusion: The higher prevalence of Covid-19 in ASD patients along with the significant correlations with important clinical features and therapeutic regimens suggests the need to develop targeted prevention/management strategies during the current pandemic wave.nonenoneFerri C, Giuggioli D, Raimondo V, L'Andolina M, Dagna L, Tavoni A, Caso F, Ursini F, Piero R, Caminiti M, Foti R, Riccieri V, Guiducci S, Pellegrini R, Zanatta E, Varcasia G, Olivo D, Gigliotti P, Cuomo G, Murdaca G, Cecchetti R, De Angelis R, Romeo N, Ingegnoli F, Cozzi F, Codullo V, Cavazzana I, Colaci M, Abignano G, De Santis M, Lubrano E, Fusaro E, Rossa AD, Spinella A, Lumetti F, De Luca G, Bellando-Randone S, Visalli E, Dal Bosco Y, Amato G, Giannini D, Bilia S, Masini F, Pellegrino G, Pigatto E, Generali E, Mariano GP, Pettiti G, Zanframundo G, Brittelli R, Aiello V, Caminiti R, Scorpiniti D, Ferrari T, Campochiaro C, Brusi V, Fredi M, Moschetti L, Cacciapaglia F, Gragnani L, Monti M, Lorini S, Paparo SR, Ragusa F, Mazzi V, Elia G, Ferrari SM, Di Cola I, Vadacca M, Lorusso S, Barsotti S, Aprile ML, Marco T, Miccoli M, Bosello S, Matucci-Cerinic M, D'Angelo S, Doria A, Franceschini F, Meliconi R, Iannone F, Giacomelli R, Zignego AL, Varcasia P, Antonelli A.Ferri, C; Giuggioli, D; Raimondo, V; L'Andolina, M; Dagna, L; Tavoni, A; Caso, F; Ursini, F; Piero, R; Caminiti, M; Foti, R; Riccieri, V; Guiducci, S; Pellegrini, R; Zanatta, E; Varcasia, G; Olivo, D; Gigliotti, P; Cuomo, G; Murdaca, G; Cecchetti, R; De Angelis, R; Romeo, N; Ingegnoli, F; Cozzi, F; Codullo, V; Cavazzana, I; Colaci, M; Abignano, G; De Santis, M; Lubrano, E; Fusaro, E; Rossa, Ad; Spinella, A; Lumetti, F; De Luca, G; Bellando-Randone, S; Visalli, E; Dal Bosco, Y; Amato, G; Giannini, D; Bilia, S; Masini, F; Pellegrino, G; Pigatto, E; Generali, E; Mariano, Gp; Pettiti, G; Zanframundo, G; Brittelli, R; Aiello, V; Caminiti, R; Scorpiniti, D; Ferrari, T; Campochiaro, C; Brusi, V; Fredi, M; Moschetti, L; Cacciapaglia, F; Gragnani, L; Monti, M; Lorini, S; Paparo, Sr; Ragusa, F; Mazzi, V; Elia, G; Ferrari, Sm; Di Cola, I; Vadacca, M; Lorusso, S; Barsotti, S; Aprile, Ml; Marco, T; Miccoli, M; Bosello, S; Matucci-Cerinic, M; D'Angelo, S; Doria, A; Franceschini, F; Meliconi, R; Iannone, F; Giacomelli, R; Zignego, Al; Varcasia, P; Antonelli, A