Background: Individuals with Chronic Inflammatory Diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the potency of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management. Methods: We conducted a prospective assessment of mRNA-based vaccine immunogenicity in 133 adults with CIDs and 53 immunocompetent controls. Blood from participants over 18 years of age was collected before initial immunization and 1-2 weeks after the second immunization. Serum anti-SARS-CoV-2 spike (S) IgG+ binding, neutralizing antibody titers, and circulating S-specific plasmablasts were quantified to assess the magnitude and quality of the humoral response following vaccination. Results: Compared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 10-fold reduction in humoral responses, respectively (p<0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analysis (P<0.0001, P=0.0023, respectively). Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization. Conclusions: CID patients treated with immunosuppressive therapies exhibit impaired SARS-CoV-2 vaccine-induced immunity, with glucocorticoids and B cell depletion therapy more severely impeding optimal responses.

Whispering-Gallery-Mode (WGM) resonators are emerging as an excellent platform to study optical phenomena resulting from enhanced light-matter interactions due to their superior capability to confine photons for extended periods of time. The monolithic fabrication process to achieve ultra-high-Q WGM resonators without the need to align multiple optical components, as needed in traditional design of resonators based on precise arrangement of mirrors, is especially attractive. Here we explain how to process a layer of thin film doped with optical gain medium, which is prepared by wet chemical synthesis, into WGM structures on silicon wafer to achieve arrays of ultra-low threshold on-chip microlasers. We can adjust the dopant species and concentration easily by tailoring the chemical compositions in the precursor solution. Lasing in different spectral windows from visible to infrared was observed in the experiments. In particular, we investigated nanoparticle sensing applications of the on-chip WGM microlasers by taking advantages of the narrow linewidths and the splitting of lasing modes arising from their interactions with nano-scale structures. It has been found that a nanoparticle as small as ten nanometers in radius could split a lasing mode in a WGM resonator into two spectrally separated lasing lines. Subsequently, when these lasing lines are photo-mixed at a photodetector a heterodyne beat note is generated which can be processed to signal the detection of individual nanoparticles. We have demonstrated detection of virions, dielectric and metallic nanoparticles by monitoring the changes in this self-heterodyning beat note of the split lasing modes. The built-in self-heterodyne method achieved in this monolithic WGM microlaser provides an ultrasensitive scheme for detecting and measuring nanoparticles at single particle resolution, with a theoretical detection limit of one nanometer.