Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19

Abstract

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.

Anti-IL5 Drugs in COVID-19 Patients: Role of Eosinophils in SARS-CoV-2-Induced Immunopathology

“…Conversely, IL-4 did not diverge between the two groups (Lucas et al, 2020). The last result is confirmed by another observational study (Mann et al, 2020). Nevertheless, IL-4, IL-5, and IL-13 displayed a trend toward an increase in the clinical scenario of severe COVID-19, and a reason for the interest is the importance of IL-5 to predict mortality, with a predictive value of around 0.73 (Lucas et al, 2020).…”

Management of hospitalised adults with coronavirus disease 2019 (COVID-19): a European Respiratory Society living guideline

“…Summary of evidence: It is clear that excessive inflammation and a dysregulated immune response play an important role in the progression of severe COVID-19, and therefore there is a strong scientific rationale for the use of anti-inflammatory treatments, particularly in patients with the most severe disease [ 20 , 21 , 44 , 45 ]. We reviewed data for 6 randomised trials and one existing meta-analysis [ 31 , 46 – 49 ].…”

Physical phenotype of blood cells is altered in COVID-19

“…In inflammatory disease, monocytes can contribute to the immune response either directly or via differentiation into dendritic cells or macrophages. Therefore it is not surprising that altered monocyte phenotype and function is characteristic for COVID-19 patients (1). Examination of monocytes with RT-DC revealed a significant change in monocyte size ( p < .0001, χ 2 = 30.6, ε 2 = 0.57) triggered by the appearance of larger monocytes during COVID-19 (Figure 4 A-D).…”

“…Peripheral blood is a key body fluid analyzed during the diagnostic routine, including infectious disease diagnostics. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to the clinical syndrome coronavirus disease 2019 (COVID-19), which is accompanied by changes in numbers and phenotypes of blood cells (1). Typically, various immune cells such as T-lymphocytes, monocytes and macrophages get activated and contribute to the so-called hyper-inflammatory response (2).…”