Psychological Fragility in an Italian Cohort of Systemic Sclerosis Patients During COVID-19 Pandemic Category: Short Communication.

Objective: This work aims to evaluate the prevalence of anxiety and COVID-19-related fear in systemic sclerosis (SSc) patients during the second and third waves of the SARS-CoV-2 pandemic in Italy and their possible associated factors. Methods: A cohort study was carried out on 114 SSc patients referred to our Scleroderma Clinic, matched for sex and age. Twenty-eight of them had missed scheduled examinations during the October 2020-March 2021 period and 86 has attended regular outpatient visits during the same period. Both groups were administered (by telephone for cases and in-person for controls) the Generalized Anxiety Disorder Scale-7 (GAD-7) questionnaire and the validated on SSc patients COVID-19 Fears Questionnaire for Chronic Medical Conditions (COVID-19 Fears). Concurrent factors related to higher scores were investigated in patients who did not have an outpatient follow-up. Results: The missing group had significantly more patients scoring ≥8 on the GAD-7 questionnaire [22 (78.6%) vs 16 (18.6%), p < 0.0001] and significantly higher scores on the COVID-19 Fears questionnaire (median [quartiles] 31.5 [26.25;37.25] vs 20 [13.75;28], p < 0.0001) than the attending group. Multivariate analysis performed on the missing patients group showed a significant association of the lack of work and ongoing therapy for anxiety/depression with GAD-7 (p = 0.0275 and p = 0.0188) and COVID-19 Fears score (p = 0.0016 and p = 0.0099). Conclusion: Anxiety disorder and COVID-19-related fear were greater in SSc patients who missed regular follow-ups and are associated with a lack of work activity. These findings aim to identify a subgroup deserving attention regarding risk factors for missed periodic controls.

Autophagy Hijacking in PBMC From COVID-19 Patients Results in Lymphopenia.

Autophagy is a homeostatic process responsible for the self-digestion of intracellular components and antimicrobial defense by inducing the degradation of pathogens into autophagolysosomes. Recent findings suggest an involvement of this process in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the role of autophagy in the immunological mechanisms of coronavirus disease 2019 (COVID-19) pathogenesis remains largely unexplored. This study reveals the presence of autophagy defects in peripheral immune cells from COVID-19 patients. The impairment of the autophagy process resulted in a higher percentage of lymphocytes undergoing apoptosis in COVID-19 patients. Moreover, the inverse correlation between autophagy markers levels and peripheral lymphocyte counts in COVID-19 patients confirms how a defect in autophagy might contribute to lymphopenia, causing a reduction in the activation of viral defense. These results provided intriguing data that could help in understanding the cellular underlying mechanisms in COVID-19 infection, especially in severe forms.

Prevalence and Death Rate of COVID-19 in Autoimmune Systemic Diseases in the First Three Pandemic Waves. Relationship with 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.

Lack of cross-reactivity between rheumatoid factor IgM and anti-S1 receptor binding domain of SARS-CoV-2 IgM: a case-control study.

OBJECTIVES: Since the onset of the COVID-19 outbreak, concern has been raised about reliability of SARS-CoV-2 serological tests in people with serum positivity for rheumatoid factor (RF), due to its ability to interfere during tests carried out with immunoassay techniques, leading to false positive results. The aim of this study was to analyse, on sera from RF seropositive rheumatoid arthritis (RA) patients, the interference between RF IgM and anti-S1 RBD IgM. METHODS: The study was conducted on consecutive patients affected by RF seropositive RA and, as control group, COVID-19 patients with SARS-CoV-2 pneumonia hospitalised at Sapienza University of Rome from April 2020 and April 2021. Serum samples from COVID-19 patients during their hospitalisation were collected, while RA subjects' samples were harvested prior to the onset of the COVID-19 pandemic. All samples were tested for RF IgM using nephelometry and ELIA, and for anti-S1 RBD IgM by ELISA. RESULTS: Forty RF seropositive RA and 42 COVID-19 patients were enrolled. In all RA patients, both nephelometric assay and ELIA showed RF IgM positivity, while only one patient of the control group tested positive for RF IgM by nephelometric assay and ELIA. IgM directed to S1 RBD were not detected in sera of RA patients, while all COVID-19 patients presented anti-S1 RBD IgM (median anti-S1 RBD IgM COVID-19 vs. RA: 368.5 IU/mL, IQR 654 IU/mL vs. 18.45 IU/mL, IQR 20 IU/mL; p<0.0001). CONCLUSIONS: This study confirmed the lack of cross-reactivity between RF and anti-S1 RBD IgM, offering to clinicians a valuable tool for a better management of RA patients undergoing SARSCoV-2 serological tests.

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

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: This study aims 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. METHODS: 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 the 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 the absence of a swab testing). RESULTS: A significantly higher prevalence of definite plus highly suspected Covid-19 compared to the 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 a 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.

COVID-19 and systemic sclerosis: analysis of lifestyle changes during the SARS-CoV-2 pandemic in an Italian single-center cohort.

The outbreak of SARS-CoV-2 has changed the habits and lives of people worldwide. Patients affected by systemic sclerosis (SSc) experienced constant fear because of their immunocompromised status. The aim of this study was to investigate the prevalence of SARS-CoV-2 infection and to analyze the lifestyle changes in a single-center cohort of SSc patients and if these changes were more severe than in the general population. During the Italian lockdown, we supplied two surveys to our 184 SSc patients. In the first one, filled by 110 patients, we asked if SARS-CoV-2 had infected them or if they experienced signs and symptoms consistent with COVID-19. The second survey, performed by 79 SSc patients and 63 healthy subjects, included questions about the lifestyle adopted during this specific period. Among our patients, COVID-19 was diagnosed only in one case, while three other subjects reported signs and symptoms suggestive for the disease. Regarding the second survey, our patients greatly changed their lifestyle during the pandemic, adopting more restrictive isolation measures, because of their awareness of frailty. To date, we do not dispose of enough data to speculate about the risk of COVID-19 among immunocompromised patients, although in our SSc patients their frailty seems to have been their shelter. Pending more accurate epidemiological studies, it is essential to share as much data as possible to better understand the impact of COVID-19 on SSc patients' health. Key points • The lifestyle adopted by SSc patients during the first months of COVID-19 pandemic was characterized by more stringent isolation rules than general population. • The prudential behavior of patients with SSc during Italian lockdown should be considered as a possible bias when analyzing the risk of SARS-CoV-2 disease in these subjects, as well as a protective factor against infection.