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Introduction The overlap between systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM) is known as Scleromyositis. Most cases of overlap are SSc-polymyositis/dermatomyositis. Anti-Ku, anti-PM/Scl 75, and anti-PM/Scl 100 autoantibodies are associated with this overlap. SARS-CoV-2 infection and vaccines have been associated with these findings based on IIM; however, the data are limited. Our study aimed to evaluate changes in PM-Scl100, PM-Scl75, and anti-Ku antibody positivity before and during the pandemic, in a large sample of Hispanic patients.Material and Methods We conducted a cross-sectional study from July 2016 to December 2021 in the rheumatology department of the university hospital in Monterrey, Mexico, including all Hispanic patients with moderate or strong positivity (>35) in immunoblot panels for inflammatory myopathies using the EUROLINE Autoimmune Inflammatory Myopathies panel. We divided patients into two groups: before COVID-19 (July 2016-February 2019) and during the health emergency (March 2020-December 2021). To compare the prevalence and medians between groups, the Chi-Square Test and Mann-Whitney´s U test were employed, as appropriate; p-value < 0.05 was considered statistically significant. The analysis was with SPSS v. 27. Approved by the institutional ethics committee (RE24-00004).Results A total of 483 panels were performed, with 416 patients (86.12%) having any positivity for at least one autoantibody. Before the COVID-19 health emergency, 256 panels were performed, and during the health emergency, a total of 227. No statistically significant differences were observed in the prevalence of anti-Ku antibodies (p = 0.689), PM-Scl75 (p = 0.475), PM-Scl100 (p = 0.741), and also for the rest of the antibodies in the panel, except: Ro52 and PL-7. During the health emergency, half of the autoantibodies (anti-Ku, PM-Scl75, PM-Scl100, Jo-1, SAE, MDA5, Mi-2b, and NXP2) did not show an increase in signal intensity. Antibodies with significant differences were Ro52, EJ, PL-7, OJ, PL-12, SRP, TIF1-gamma and Mi-2alpha.Conclusions The prevalence and signal intensity of anti-Ku, PM-Scl75, and PM-Scl100 antibodies remained stable before and during the COVID-19 pandemic. These findings suggest that overlap-associated antibodies in SSc and IIM are less susceptible to virus-driven immune perturbation and remain reliable biomarkers across immunologic contexts. By contrast, certain Myositis-Specific Antibodies showed increased intensity during the pandemic, underscoring differential responses among autoantibody systems. Our results provide novel insights into the serologic behavior of systemic sclerosis-related autoantibodies in an underrepresented Hispanic cohort, reinforcing their role in disease stratification and supporting their stability as diagnostic tools, even during periods of global immune disruption.