Prevalence and Death Rate of COVID-19 in Autoimmune Systemic Diseases in the
First Three Pandemic Waves. Relationship with Disease Subgroups and Ongoing
Therapies
Authors: 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 Alessandro 
Published: June 2022

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.

Method:
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.