Multi-dimensional and longitudinal systems profiling reveals predictive pattern of severe COVID-19

Abstract

COVID-19 is a respiratory tract infection that can affect multiple organ systems. Predicting the severity and clinical outcome of individual patients is a major unmet clinical need that remains challenging due to intra- and inter-patient variability. Here, we longitudinally profiled and integrated more than 150 clinical, laboratory and immunological parameters of 173 patients with mild to fatal COVID-19. Using systems biology, we detected progressive dysregulation of multiple parameters indicative of organ damage that correlated with disease severity, particularly affecting kidneys, hepatobiliary system, and immune landscape. By performing unsupervised clustering and trajectory analysis, we identified T and B cell depletion as early indicators of a complicated disease course. In addition, markers of hepatobiliary damage emerged as robust predictor of lethal outcome in critically ill patients. This allowed us to propose a novel clinical CO VID-19 S everi T y (COST) score that distinguishes complicated disease trajectories and predicts lethal outcome in critically ill patients.

The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19

“…Due to their functional role in pain perception, anxiety, depression, and inflammatory symptoms 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 they are well compatible with the spectrum of symptoms in PASC. While the plasma levels of all three cytokines are highly elevated in acute COVID-19, 37 , 74 , 75 IL-6 in particular represents a key inflammatory driver of SARS-CoV-2-dependent immune pathogenesis as highlighted by its suitability as marker for severity and survival of COVID-19 76 , 77 and the benefit of IL-6-directed treatment in hospitalized patients when combined with corticosteroids as found by the REMAP-CAP 78 and RECOVERY 79 trials. It should be noted that IL-6 plasma levels in COVID-19 are lower as compared with other conditions like sepsis, acute respiratory distress syndrome (ARDS), or chimeric antigen receptor T cell-associated cytokine release syndrome (CAR-T CRS).…”

Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease

“…The quality and breadth of CD4+ and CD8+ T cell response plays a key role in COVID-19 resolution and modulation of disease severity. B and T cell depletion are early indicators of severe disease development and along with markers of liver damage, act as predictors of mortality in severe COVID-19 patients [ 194 ]. Regulatory T-cells on the other hand control immune system homeostasis and self-tolerance by negative regulation of effector functions, activation, and proliferation of immune cells [ 195 ].…”

Longitudinally monitored immune biomarkers predict the timing of COVID-19 outcomes

“…Unlike admission clinical and laboratory values, longitudinal information mirroring the evolution of disease during hospitalization might be better suited to predict disease outcome far downstream [28]. Studies on longitudinal data have mostly focused on trajectory profiling, unraveling valuable time-dependent associations between biomarkers and disease severity [29][30][31][32][33]. However, integration of longitudinal clinical data within a machine learning framework has rarely been reported [28,34].…”