BACKGROUND Elevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare with those observed in critically ill patients with acute respiratory distress syndrome (ARDS) or sepsis due to other causes. METHODS We used a Luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1β, IL-1RA, IL-6, IL-8, IL-18, and TNF-α) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis. RESULTS Fifteen hospitalized COVID-19 patients, 9 of whom were critically ill, were compared with critically ill patients with ARDS ( n = 12) or sepsis ( n = 16). There were no statistically significant differences in baseline levels of IL-1β, IL-1RA, IL-6, IL-8, IL-18, and TNF-α between patients with COVID-19 and critically ill controls with ARDS or sepsis. CONCLUSION Levels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted. FUNDING Funding was received from NHLBI K23 HL125663 (AJR); The Bill and Melinda Gates Foundation OPP1113682 (AJR and CAB); Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687 NIH/NIAID U19AI057229-16; Stanford Maternal Child Health Research Institute; and Chan Zuckerberg Biohub (CAB).

Aims To describe the effects of the COVID-19 pandemic on adults with T1D or T2D in the U.S. Methods Participants, recruited from the Taking Control of Your Diabetes Research Registry, were ≥19 years old and diagnosed with either T1D or T2D for ≥12 months. Participants completed an online survey on a HIPAA-protected platform. Results Completed surveys were received from 763 T1Ds and 619 T2Ds. Average T1D age was 53.3 (SD = 15.3); average T2D age was 64.9 (SD = 10.3). Both samples were predominantly female, non-Hispanic white and well-educated. Average self-reported HbA1c was 6.9 (SD = 1.0; 52 mmol/mol) for T1Ds and 7.1 (SD = 1.1; 54 mmol/mol) for T2Ds. About 40% of respondents reported that all of their diabetes healthcare appointments at the time were cancelled or postponed, 40% reported a switch to telehealth appointments and almost half reported lower overall satisfaction with these visits (compared to pre-pandemic). There were widespread increases in general and diabetes-related stress and social isolation, and negative effects on disease management. About 25% reported increases in highs, lows, and glucose variability in both groups. Conclusion There has been a substantive increase in level of diabetes-related and general life stress and social isolation due to the pandemic, with a significant impact on disease management.

Rationale: Elevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare to those observed in critically ill patients with ARDS or sepsis due to other causes.

The widespread presence of autoantibodies in acute infection with SARS-CoV-2 is increasingly recognized, but the prevalence of autoantibodies in non–SARS-CoV-2 infections and critical illness has not yet been reported. We profiled IgG autoantibodies in 267 patients from 5 independent cohorts with non–SARS-CoV-2 viral, bacterial, and noninfectious critical illness. Serum samples were screened using Luminex arrays that included 58 cytokines and 55 autoantigens, many of which are associated with connective tissue diseases (CTDs). Samples positive for anti-cytokine antibodies were tested for receptor blocking activity using cell-based functional assays. Anti-cytokine antibodies were identified in > 50% of patients across all 5 acutely ill cohorts. In critically ill patients, anti-cytokine antibodies were far more common in infected versus uninfected patients. In cell-based functional assays, 11 of 39 samples positive for select anti-cytokine antibodies displayed receptor blocking activity against surface receptors for Type I IFN, GM-CSF, and IL-6. Autoantibodies against CTD-associated autoantigens were also commonly observed, including newly detected antibodies that emerged in longitudinal samples. These findings demonstrate that anti-cytokine and autoantibodies are common across different viral and nonviral infections and range in severity of illness.