Stepwise asynchronous telehealth assessment of patients with suspected axial spondyloarthritis: results from a pilot study.

Patients with axial spondyloarthritis (axSpA) suffer from one of the longest diagnostic delays among all rheumatic diseases. Telemedicine (TM) may reduce this diagnostic delay by providing easy access to care. Diagnostic rheumatology telehealth studies are scarce and largely limited to traditional synchronous approaches such as resource-intensive video and telephone consultations. The aim of this study was to investigate a stepwise asynchronous telemedicine-based diagnostic approach in patients with suspected axSpA. Patients with suspected axSpA completed a fully automated digital symptom assessment using two symptom checkers (SC) (bechterew-check and Ada). Secondly, a hybrid stepwise asynchronous TM approach was investigated. Three physicians and two medical students were given sequential access to SC symptom reports, laboratory and imaging results. After each step, participants had to state if axSpA was present or not (yes/no) and had to rate their perceived decision confidence. Results were compared to the final diagnosis of the treating rheumatologist. 17 (47.2%) of 36 included patients were diagnosed with axSpA. Diagnostic accuracy of bechterew-check, Ada, TM students and TM physicians was 47.2%, 58.3%, 76.4% and 88.9% respectively. Access to imaging results significantly increased sensitivity of TM-physicians (p < 0.05). Mean diagnostic confidence of false axSpA classification was not significantly lower compared to correct axSpA classification for both students and physicians. This study underpins the potential of asynchronous physician-based telemedicine for patients with suspected axSpA. Similarly, the results highlight the need for sufficient information, especially imaging results to ensure a correct diagnosis. Further studies are needed to investigate other rheumatic diseases and telediagnostic approaches.

Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease

ObjectiveTo investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. MethodsEstablished patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. ResultsAlthough healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. ConclusionsIn two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines. KEY MESSAGESO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIThe impact of COVID-19 has been felt across the globe and new hope has arisen with the approval of mRNA vaccines against the SARS-CoV-2. Studies have shown immunogenicity and efficacy rates of over 90% in the immunocompetent adult population. However, there is a lack of knowledge surrounding the response of patients with immune-mediated inflammatory diseases (IMIDs) who may also be on immunomodulatory medications. C_LIO_LIPatients with IMID have been shown to have attenuated immune responses to seasonal influenza vaccination. C_LI What does this study add?O_LIThis study looks at the humoral and cellular immune response to two doses of BNT162b2 mRNA COVID-19 Vaccine in participants with IMID (on immunomodulators) compared with healthy controls. C_LIO_LIIndividuals with IMID on methotrexate demonstrate up to a 62% reduced rate of adequate immunogenicity to the BNT162b2 mRNA vaccination. Those on anti-cytokine or non-methotrexate oral medications demonstrate similar levels of immunogenicity as healthy controls (greater than 90%). C_LIO_LISimilarly, vaccination did not induce an activated CD8+ T cell response in participants on background methotrexate, unlike healthy controls and patients with IMID not receiving methotrexate. C_LI How might this impact of clinical practice or future developments?O_LIThese results suggest that patients on methotrexate may need alternate vaccination strategies such as additional doses of vaccine, dose modification of methotrexate, or even a temporary discontinuation of this drug. Further studies will be required to explore the effect of these approaches on mRNA vaccine immunogenicity. C_LI

Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. Here, we report that low plasma interleukin-3 (IL-3) levels were associated with increased severity and mortality during SARS-CoV-2 infections. IL-3 promoted the recruitment of antiviral circulating plasmacytoid dendritic cells (pDCs) into the airways by stimulating CXCL12 secretion from pulmonary CD123+ epithelial cells. This study identifies IL-3 as a predictive disease marker and potential therapeutic target for SARS-CoV-2 infections.Competing Interest StatementThe authors have declared no competing interest.View Full Text