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The COVID-19 pandemic has affected more than 10 million people worldwide with mortality exceeding3 half a million patients. Risk factors associated with severe disease and mortality include advanced age,4 hypertension, diabetes, and obesity.1 Clear mechanistic understanding of how these comorbidities5 converge to enable severe infection is lacking. Notably each of these risk factors pathologically disrupts6 the lipidome and this disruption may be a unifying feature of severe COVID-19.1-7 Here we provide the first in depth interrogation of lipidomic changes, including structural-lipids as well as the eicosanoids and docosanoids lipid mediators (LMs), that mark COVID-19 disease severity. Our data reveal that progression from moderate to severe disease is marked by a loss of specific immune regulatory LMs and increased pro-inflammatory species. Given the important immune regulatory role of LMs, these data provide mechanistic insight into the immune balance in COVID-19 and potential targets for therapy with currently approved pharmaceuticals.8

A growing body of evidence indicates sex differences in the clinical outcomes of coronavirus disease 2019 (COVID-19)1-4. However, whether immune responses against SARS-CoV-2 differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown. In this study, we examined sex differences in viral loads, SARS-CoV-2-specific antibody titers, plasma cytokines, as well as blood cell phenotyping in COVID-19 patients. By focusing our analysis on patients with mild to moderate disease who had not received immunomodulatory medications, our results revealed that male patients had higher plasma levels of innate immune cytokines and chemokines including IL-8, IL-18, and CCL5, along with more robust induction of non-classical monocytes. In contrast, female patients mounted significantly more robust T cell activation than male patients during SARS-CoV-2 infection, which was sustained in old age. Importantly, we found that a poor T cell response negatively correlated with patients’ age and was predictive of worse disease outcome in male patients, but not in female patients. Conversely, higher innate immune cytokines in female patients associated with worse disease progression, but not in male patients. These findings reveal a possible explanation underlying observed sex biases in COVID-19, and provide important basis for the development of sex-based approach to the treatment and care of men and women with COVID-19.

Rationale and Objective Acute kidney injury (AKI) is common in patients with COVID-19 and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. We investigated the association between urinary biomarkers with adverse kidney outcomes among patients hospitalized with COVID-19. Study Design Prospective cohort study. Setting and Participants Patients hospitalized with COVID-19 (n=153) at 2 academic medical centers between April and June 2020. Exposures 19 urinary biomarkers of injury, inflammation, and repair. Outcomes Composite of KDIGO stage 3 AKI, requirement for dialysis, or death within 60 days of hospital admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings. Analytic Approach Time-varying Cox proportional hazards regression to associate biomarker level with composite outcome. Results Out of 153 patients, 24 (15.7%) experienced the primary outcome. Two-fold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR: 1.34; 95% CI: 1.14-1.57), monocyte chemoattractant protein (MCP-1) (HR: 1.42; 95% CI: 1.09-1.84), and kidney injury molecule-1 (KIM-1) (HR: 2.03; 95% CI: 1.38-2.99) were associated with highest risk of sustaining primary composite outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR 0.61; 95% CI: 0.47-0.79). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. The degree of kidney injury by biomarker level in COVID-19 was comparable to other settings of clinical AKI. There was evidence of subclinical AKI in COVID-19 patients based on elevated injury biomarker level in patients without clinical AKI defined by serum creatinine. Limitations Small sample size with low number of composite outcome events. Conclusion Urinary biomarkers are associated with adverse kidney outcomes in patients hospitalized with COVID-19 and may provide valuable information to monitor kidney disease progression and recovery., Graphical abstract