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

The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations

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

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

Prevalence and death rate of COVID-19 in systemic autoimmune diseases in the first three pandemic waves. Relationship to disease subgroups and ongoing therapies

Objective: Autoimmune systemic diseases (ASD) represent a predisposing condition to COVID-19. Our prospective, observational multicenter telephone survey study aimed to investigate the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients. Methods: The study included 3,918 ASD pts (815 M, 3103 F; mean age 59 +/- 12SD years) consecutively recruited between March 2020 and May 2021 at the 36 referral centers of COVID-19 and ASD Italian Study Group. The possible development of COVID-19 was recorded by means of a telephone survey using a standardized symptom assessment questionnaire. Results: ASD patients showed a significantly higher prevalence of COVID-19 (8.37% vs. 6.49%; p<0.0001) but a death rate statistically comparable to the Italian general population (3.65% vs. 2.95%). Among the 328 ASD patients developing COVID-19, 17% needed hospitalization, while mild-moderate manifestations were observed in 83% of cases. Moreover, 12/57 hospitalized patients died due to severe interstitial pneumonia and/or cardiovascular events; systemic sclerosis (SSc) patients showed a significantly higher COVID-19-related death rate compared to the general population (6.29% vs. 2.95%; p=0.018). Major adverse prognostic factors to develop COVID-19 were: older age, male gender, SSc, pre-existing ASD-related interstitial lung involvement, and long-term steroid treatment. Of note, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs. 46.99%; p=0.000), as well as the SSc patients treated with low dose aspirin (with 5.57% vs. without 27.84%; p=0.000). Conclusion: During the first three pandemic waves, ASD patients showed a death rate comparable to the general population despite the significantly higher prevalence of COVID-19. A significantly increased COVID-19-related mortality was recorded in only SSc patients' subgroup, possibly favored by preexisting lung fibrosis. Moreover, ongoing long-term treatment with csDMARDs in ASD might usefully contribute to the generally positive outcomes of this frail patients' population

Prevalence and death rate of COVID-19 in systemic autoimmune diseases in the first three pandemic waves. Relationship to disease subgroups and ongoing therapies

none84noAutoimmune systemic diseases (ASD) represent a predisposing condition to COVID-19. Our prospective, observational multicenter telephone survey study aimed to investigate the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients.Ferri, Clodoveo; Raimondo, Vincenzo; Gragnani, Laura; Giuggioli, Dilia; Dagna, Lorenzo; Tavoni, Antonio; Ursini, Francesco; L'Andolina, Massimo; Caso, Francesco; Ruscitti, Piero; Caminiti, Maurizio; Foti, Rosario; Riccieri, Valeria; Guiducci, Serena; Pellegrini, Roberta; Zanatta, Elisabetta; Varcasia, Giuseppe; Olivo, Domenico; Gigliotti, Pietro; Cuomo, Giovanna; Murdaca, Giuseppe; Cecchetti, Riccardo; De Angelis, Rossella; Romeo, Nicoletta; Ingegnoli, Francesca; Cozzi, Franco; Codullo, Veronica; Cavazzana, Ilaria; Colaci, Michele; Abignano, Giuseppina; De Santis, Maria; Lubrano, Ennio; Fusaro, Enrico; Spinella, Amelia; Lumetti, Federica; De Luca, Giacomo; Bellando-Randone, Silvia; Visalli, Elisa; Bosco, Ylenia Dal; Amato, Giorgio; Giannini, Daiana; Bilia, Silvia; Masini, Francesco; Pellegrino, Greta; Pigatto, Erika; Generali, Elena; Mariano, Giuseppa Pagano; Pettiti, Giorgio; Zanframundo, Giovanni; Brittelli, Raffaele; Aiello, Vincenzo; Caminiti, Rodolfo; Scorpiniti, Daniela; Ferrari, Tommaso; Campochiaro, Corrado; Brusi, Veronica; Fredi, Micaela; Moschetti, Liala; Cacciapaglia, Fabio; Paparo, Sabrina Rosaria; Ragusa, Francesca; Mazzi, Valeria; Elia, Giusy; Ferrari, Silvia Martina; Di Cola, Ilenia; Vadacca, Marta; Lorusso, Sebastiano; Monti, Monica; Lorini, Serena; Aprile, Maria Letizia; Tasso, Marco; Miccoli, Mario; Bosello, Silvia; D'Angelo, Salvatore; Doria, Andrea; Franceschini, Franco; Meliconi, Riccardo; Matucci-Cerinic, Marco; Iannone, Florenzo; Giacomelli, Roberto; Salvarani, Carlo; Zignego, Anna Linda; Fallahi, Poupak; Antonelli, AlessandroFerri, Clodoveo; Raimondo, Vincenzo; Gragnani, Laura; Giuggioli, Dilia; Dagna, Lorenzo; Tavoni, Antonio; Ursini, Francesco; L'Andolina, Massimo; Caso, Francesco; Ruscitti, Piero; Caminiti, Maurizio; Foti, Rosario; Riccieri, Valeria; Guiducci, Serena; Pellegrini, Roberta; Zanatta, Elisabetta; Varcasia, Giuseppe; Olivo, Domenico; Gigliotti, Pietro; Cuomo, Giovanna; Murdaca, Giuseppe; Cecchetti, Riccardo; De Angelis, Rossella; Romeo, Nicoletta; Ingegnoli, Francesca; Cozzi, Franco; Codullo, Veronica; Cavazzana, Ilaria; Colaci, Michele; Abignano, Giuseppina; De Santis, Maria; Lubrano, Ennio; Fusaro, Enrico; Spinella, Amelia; Lumetti, Federica; De Luca, Giacomo; Bellando-Randone, Silvia; Visalli, Elisa; Bosco, Ylenia Dal; Amato, Giorgio; Giannini, Daiana; Bilia, Silvia; Masini, Francesco; Pellegrino, Greta; Pigatto, Erika; Generali, Elena; Mariano, Giuseppa Pagano; Pettiti, Giorgio; Zanframundo, Giovanni; Brittelli, Raffaele; Aiello, Vincenzo; Caminiti, Rodolfo; Scorpiniti, Daniela; Ferrari, Tommaso; Campochiaro, Corrado; Brusi, Veronica; Fredi, Micaela; Moschetti, Liala; Cacciapaglia, Fabio; Paparo, Sabrina Rosaria; Ragusa, Francesca; Mazzi, Valeria; Elia, Giusy; Ferrari, Silvia Martina; Di Cola, Ilenia; Vadacca, Marta; Lorusso, Sebastiano; Monti, Monica; Lorini, Serena; Aprile, Maria Letizia; Tasso, Marco; Miccoli, Mario; Bosello, Silvia; D'Angelo, Salvatore; Doria, Andrea; Franceschini, Franco; Meliconi, Riccardo; Matucci-Cerinic, Marco; Iannone, Florenzo; Giacomelli, Roberto; Salvarani, Carlo; Zignego, Anna Linda; Fallahi, Poupak; Antonelli, Alessandr