Nocebo-Prone Behaviour in Patients with Autoimmune Rheumatic Diseases during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic is associated with emotional distress and significant disruptions in health-care services. These are key players in the development of nocebo phenomena. We aimed to investigate nocebo-prone behaviour in patients with autoimmune rheumatic diseases (ARD) amid the COVID-19 pandemic-associated lockdown. METHODS: Consecutive patients were telephone-interviewed during the COVID-19 pandemic in Greece. Clinical and socioeconomic characteristics (eg, level of education) were recorded. For nocebo behaviour, a four-item validated questionnaire (Q-No, cut-off score>15), was used. Results were compared with pre-COVID-19 Q-No scores collected from patients followed-up in our department. RESULTS: Nocebo behaviour was detected in 51/500 (10.2%) individuals. In patients with nocebo behaviour, use of anti-hypertensives was less common (17.6% vs 31.8%, p=0.04), but a higher level of education was more common (58.8% vs 35.9%, p=0.002), compared with patients with Q-No score ≤15; the latter retained statistical significance in multivariate regression analysis (p=0.009, OR [95%CI]: 2.29, [1.23-4.25]). Total Q-No scores were higher in the COVID-19-period compared to the pre-COVID-19 era [median (range); 12 (4-20) vs 11 (4-20), p=0.02]. Among 78 patients with available Q-No questionnaires in the pre-COVID-19 era, 11 (14.1%) displayed nocebo behaviour, which increased to 16 (20.5%) amid the COVID-19 pandemic. Interim development of nocebo behaviour was also associated with higher educational level (p=0.049, OR: 3.65, 95%CI: 1.005-13.268). CONCLUSION: A considerable proportion of ARD patients manifested nocebo-prone behaviour during the COVID-19 pandemic, which was more common among those with high educational level.

Oxidative stress and endogenous DNA damage in blood mononuclear cells may predict anti-SARS-CoV-2 antibody titers after vaccination in older adults.

Immune senescence in the elderly has been associated with chronic oxidative stress and DNA damage accumulation. Herein we tested the hypothesis that increased endogenous DNA damage and oxidative stress in peripheral blood mononuclear cells of older adults associate with diminished humoral immune response to SARS-CoV-2 vaccination. Increased oxidative stress and DNA double-strand breaks (DSBs) were detected in 9 non-immunocompromised individuals aged 80-96 years compared to 11 adults aged 27-44 years, before, as well as on days 1 and 14 after the first dose, and on day 14 after the second dose of the BNT162B2-mRNA vaccine (all p < 0.05). SARS-CoV-2 vaccination induced a resolvable increase in oxidative stress and DNA damage, but individual DSB-repair efficiency was unaffected by vaccination irrespective of age, confirming vaccination safety. Individual titers of anti-Spike-Receptor Binding Domain (S-RBD)-IgG antibodies, and the neutralizing capacity of circulating anti-SARS-CoV-2 antibodies, measured on day 14 after the second dose in all participants, correlated inversely with the corresponding pre-vaccination endogenous oxidative stress and DSB levels (all p < 0.05). In particular, a strong inverse correlation of individual pre-vaccination DSB levels with both the respective anti-S-RBD-IgG antibodies titers (r = -0.867) and neutralizing capacity of circulating anti-SARS-CoV-2 antibodies (r = -0.983) among the 9 older adults was evident. These findings suggest that humoral responses to SARS-CoV-2 vaccination may be weaker when immune cells are under oxidative and/or genomic stress. Whether such measurements may serve as biomarkers of vaccine efficacy in older adults warrants further studies.

Nocebo-Prone Behavior Associated with SARS-CoV-2 Vaccine Hesitancy in Healthcare Workers.

Among healthcare workers (HCWs), SARS-CoV-2 vaccine hesitancy may be linked to a higher susceptibility to nocebo effects, i.e., adverse events (AEs) experienced after medical treatments due to negative expectations. To investigate this hypothesis a cross-sectional survey was performed with a self-completed questionnaire that included a tool (Q-No) for the identification of nocebo-prone individuals. A total of 1309 HCWs (67.2% women; 43.4% physicians; 28.4% nurses; 11.5% administrative staff; 16.6% other personnel) completed the questionnaires, among whom 237 (18.1%) had declined vaccination. Q-No scores were ≥15 in 325 participants (24.8%) suggesting nocebo-prone behavior. In a multivariate logistic regression model with Q-No score, age, gender, and occupation as independent variables, estimated odds ratios (ORs) of vaccination were 0.43 (i.e., less likely, p < 0.001) in participants with Q-No score ≥ 15 vs. Q-No score < 15, 0.58 in females vs. males (p = 0.013), and 4.7 (i.e., more likely) in physicians vs. other HCWs (p < 0.001), independent of age, which was not significantly associated with OR of vaccination. At least one adverse effect (AE) was reported by 67.5% of vaccinees, mostly local pain and flu-like symptoms. In a multivariate logistic regression model, with Q-No score, age, gender, and occupation as independent variables, estimated ORs of AE reporting were 2.0 in females vs. males (p < 0.001) and 1.47 in physicians vs. other HCWs (p = 0.017) independently of age and Q-No score, which were not significantly associated with OR of AE. These findings suggest that nocebo-prone behavior in HCWs is associated with SARS-CoV-2 vaccination hesitancy indicating a potential benefit of a campaign focused on nocebo-prone people.

Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases.

OBJECTIVE: Τo report outcomes of breakthrough COVID-19 in comparison with COVID-19 in unvaccinated patients with systemic rheumatic diseases (SRDs). METHODS: Patients with SRD with COVID-19 (vaccinated and unvaccinated) were included by their rheumatologists in a registry operated by the Greek Rheumatology Society in a voluntarily basis. Type, date and doses of SARS-CoV-2 vaccines were recorded, and demographics, type of SRD, concurrent treatment, comorbidities and COVID-19 outcomes (hospitalisation, need for oxygen supplementation and death) were compared between vaccinated and unvaccinated patients. RESULTS: Between 1 March 2020 and 31 August 2021, 195 patients with SRD with COVID-19 were included; 147 unvaccinated and 48 vaccinated with at least one dose of a SARS-CoV-2 vaccine (Pfizer n=38 or AstraZeneca n=10). Among vaccinated patients, 29 developed breakthrough COVID-19 >14 days after the second vaccine dose (fully vaccinated), while 19 between the first and <14 days after the second vaccine dose (partially vaccinated). Despite no differences in demographics, SRD type, treatment or comorbidities between unvaccinated and vaccinated patients, hospitalisation and mortality rates were higher in unvaccinated (29.3% and 4.1%, respectively) compared with partially vaccinated (21% and 0%) or fully vaccinated (10.3% and 0%) patients. CONCLUSIONS: Vaccinated patients with SRD with breakthrough COVID-19 have better outcomes compared with unvaccinated counterparts with similar disease/treatment characteristics.

Increased influenza vaccination rates in patients with autoimmune rheumatic diseases during the Covid-19 pandemic: a cross-sectional study.

To assess non-compliance and potential changes in seasonal flu vaccination coverage before and during the Covid-19 pandemic in patients with autoimmune rheumatic diseases (ARDs). Consecutive patients with ARDs followed-up in 2 tertiary hospitals were telephone-interviewed (December 12-30, 2020) regarding seasonal flu vaccination during the 2019/20 and 2020/21 time periods. Self-reported disease flares that occurred after flu vaccination, as well as reasons for non-vaccination were recorded. One thousand fifteen patients were included. The rate of flu vaccination increased from 76% before to 83% during the COVID-19 pandemic (p = 0.0001). The rate of self-reported disease flares was < 1% among vaccinated patients. Reasons for not vaccination in both periods, respectively, included: 'was not recommended by their rheumatologists' (35.0vs.12.2%, p < 0.0001), 'did not feel that they would have any benefit' (36.9 vs. 32.6%), felt unsafe to do so (27.5 vs. 30.2%), or other reasons (18.9 vs. 23.8%). By multivariate analysis, age [OR = 1.03 (95% CI 1.02-1.04)] vs. [1.04 (95% CI 1.02-1.05)] and treatment with biologics [OR = 1.66 (95% CI 1.22-2.24) vs. [1.68 (95% CI 1.19-2.38)] were independent factors associated with vaccination in both periods. These findings, although are temporally encouraging, emphasize the need for continuous campaigns aiming at increasing patients' and physicians' awareness about the benefits of vaccination.