Background: Weeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called Multisystem Inflammatory Syndrome in Children (MIS-C).Gastrointestinal symptoms are common in MIS-C patients and severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not previously been identified.Methods: Here, we analyzed biospecimens from 100 children: 19 children with MIS-C, 26 with acute COVID-19, and 55 controls. Stool was assessed for SARS-CoV-2 by RT-PCR and plasma was assessed for markers of breakdown of mucosal barrier integrity, including zonulin.Ultrasensitive antigen detection was used to probe for SARS-CoV-2 antigenemia in plasma, and immune responses were characterized. As proof of concept, we treated a MIS-C patient with larazotide, a zonulin antagonist, and monitored impact on antigenemia and clinical response. Results:We showed that in MIS-C, prolonged presence of SARS-CoV-2 in the GI tract leads to release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. The MIS-C patient treated with larazotide displayed a coinciding decrease in plasma SARS-CoV-2 Spike antigen levels, inflammatory markers, and a resultant clinical improvement above that achieved with currently available treatments. Conclusion:These mechanistic data of MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 21 million people worldwide since August 16, 2020. Compared to PCR and serology tests, SARS-CoV-2 antigen assays are underdeveloped, despite their potential to identify active infection and monitor disease progression. Methods We used Single Molecule Array (Simoa) assays to quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of coronavirus disease (COVID-19) patients. We studied plasma from 64 COVID-19 positive patients, 17 COVID-19 negative patients, and 34 pre-pandemic patients. Combined with Simoa anti-SARS-CoV-2 serological assays, we quantified changes in 31 SARS-CoV-2 biomarkers in 272 longitudinal plasma samples obtained for 39 COVID-19 patients. Data were analyzed by hierarchical clustering and were compared to longitudinal RT-PCR test results and clinical outcomes. Results SARS-CoV-2 S1 and N antigens were detectable in 41 out of 64 COVID-19 positive patients. In these patients, full antigen clearance in plasma was observed a mean ± 95%CI of 5 ± 1 days after seroconversion and nasopharyngeal RT-PCR tests reported positive results for 15 ± 5 days after viral antigen clearance. Correlation between patients with high concentrations of S1 antigen and ICU admission (77%) and time to intubation (within one day) was statistically significant. Conclusions The reported SARS-CoV-2 Simoa antigen assay is the first to detect viral antigens in the plasma of COVID-19 positive patients to date. These data show that SARS-CoV-2 viral antigens in the blood are associated with disease progression, such as respiratory failure, in COVID-19 cases with severe disease.

SARS-CoV-2 proteins were measured in longitudinal plasma samples collected from 13 participants who received two doses of mRNA-1273 vaccine. 11 of 13 participants showed detectable levels of SARS-CoV-2 protein as early as day one after first vaccine injection. Clearance of detectable SARS-CoV-2 protein correlated with production of IgG and IgA.

The oxygen, O, in air interferes with the detection of H by palladium (Pd)-based H sensors, including Pd nanowires (NWs), depressing the sensitivity and retarding the response/recovery speed in air-relative to N or Ar. Here, we describe the preparation of H sensors in which a nanofiltration layer consisting of a Zn metal-organic framework (MOF) is assembled onto Pd NWs. Polyhedron particles of Zn-based zeolite imidazole framework (ZIF-8) were synthesized on lithographically patterned Pd NWs, leading to the creation of ZIF-8/Pd NW bilayered H sensors. The ZIF-8 filter has many micropores (0.34 nm for gas diffusion) which allows for the predominant penetration of hydrogen molecules with a kinetic diameter of 0.289 nm, whereas relatively larger gas molecules including oxygen (0.345 nm) and nitrogen (0.364 nm) in air are effectively screened, resulting in superior hydrogen sensing properties. Very importantly, the Pd NWs filtered by ZIF-8 membrane (Pd NWs@ZIF-8) reduced the H response amplitude slightly (ΔR/R = 3.5% to 1% of H versus 5.9% for Pd NWs) and showed 20-fold faster recovery (7 s to 1% of H) and response (10 s to 1% of H) speed compared to that of pristine Pd NWs (164 s for response and 229 s for recovery to 1% of H). These outstanding results, which are mainly attributed to the molecular sieving and acceleration effect of ZIF-8 covered on Pd NWs, rank highest in H sensing speed among room-temperature Pd-based H sensors.