Omicron variant dominance and anti-SARS-CoV-2 vaccination are key determinants for a milder course of COVID-19 in patients with systemic autoimmune rheumatic diseases
Authors: Papagoras Charalampos , Zioga Nikoleta , Papadopoulos Vasileios , Gerolymatou Nafsika , Kalavri Eleni , Bounos Christos , Simopoulou Theodora , Fragoulis George E. , Panopoulos Stylianos , Fragiadaki Kalliopi , Evangelatos Gerasimos , Bournia Vasiliki-Kalliopi , Arida Aikaterini , Karamanakos Anastasios , Pappa Maria , Kravvariti Evrydiki , Deftereou Kleopatra , Kougkas Nikolaos , Zampeli Evangelia , Kataxaki Evangelia , Melissaropoulos Konstantinos , Barouta Georgia , Panagiotopoulos Alexandros , Koutsianas Christos , Liossis Stamatis-Nick , Georgiou Panagiotis , Dimitroulas Theodoros , Tektonidou Maria G. , Bogdanos Dimitrios P. , Elezoglou Antonia , Voulgari Paraskevi V. , Sfikakis Petros P. , Vassilopoulos Dimitrios 
Published: September 2023

Abstract
Introduction
This study aimed to determine whether the introduction of anti-SARS-CoV-2 vaccines and the dominance of the omicron variant had a significant impact on the outcome of COVID-19 in patients with systemic autoimmune rheumatic diseases (SAIRDs).

Methods
Using data entered to the Greek Rheumatology Society COVID-19 registry, we investigated the incidence of hospitalization and death due to COVID-19, during the successive periods of the pandemic according to the prevalent strain (wild-type, Alpha, Delta, Omicron) in vaccinated and unvaccinated patients. Variables independently associated with hospitalization and death were explored using multivariate regression analyses, while Kaplan–Meier curves were used to depict survival data.

Results
From August 2020 until June 30, 2022, 456 cases (70.2% females) of COVID-19 with a mean age (± SD) of 51.4 ± 14.0 years were reported. In unvaccinated patients, the proportions of hospitalization and death were 24.5% and 4%, compared to 12.5% and 0.8% in the vaccinated group (p < 0.001 for both comparisons). The rates of hospitalization for the wild-type, Alpha, Delta, and Omicron periods were 24.7%, 31.3%, 25.9%, and 8.1% respectively (p < 0.0001), while the case fatality rates were 2.7%, 4%, 7%, and 0%, respectively (p = 0.001). Using multivariable regression analysis, factors independently associated with hospitalization were infection by a non-Omicron variant, being non-vaccinated, exposure to rituximab, older age, and respiratory and cardiovascular disease. Independent predictors for death were contracting COVID-19 during the Alpha or Delta period, pulmonary disease, and older age, while being vaccinated was protective.

Conclusions
In this 2-year analysis, the rates of hospitalization and death among patients with SAIRDs have declined significantly. Vaccination and the dominance of the Omicron variant appear to be the major determinants for this shift.

Key points• During the late phase of the pandemic, the proportion of severe COVID-19 cases, defined as requiring hospitalization or resulting in death, in patients with systemic autoimmune rheumatic diseases has declined.• Anti-SARS-CoV-2 vaccination and the dominance of the Omicron strain are the key factors that have independently contributed to this shift.