Monocyte HLA‐DR Measurement by Flow Cytometry in COVID‐19 Patients: An Interim Review

Abstract

Several months after the sudden emergence of SARS‐CoV‐2 and COVID‐19, the understanding of the appropriate host immune response to a virus totally unknown of human immune surveillance is still of major importance. By international definition, COVID‐19 falls in the scope of septic syndromes (organ dysfunction due to dysregulated host response to an infection) in which immunosuppression is a significant driver of mortality. Sepsis‐induced immunosuppression is mostly defined and monitored by the measurement of decreased expression of HLA‐DR molecules on circulating monocytes (mHLA‐DR). In this interim review, we summarize the first mHLA‐DR results in COVID‐19 patients. In critically ill patients, results homogenously indicate a decreased mHLA‐DR expression, which, along with profound lymphopenia and other functional alterations, is indicative of a status of immunosuppression. © 2020 International Society for Advancement of Cytometry

HLA, Immune Response, and Susceptibility to COVID-19

“…In a study conducted by Benlyamani et al. in critically ill patients, results indicate downregulation of HLA-DR molecules in circulating monocytes, which, based on profound lymphopenia and other functional differences, create immunosuppressed conditions for host response ( 33 ).…”

COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment – A narrative review

“…Another investigation identified advanced age, male gender, underlying comorbidities, including hypertension, diabetes, obesity, chronic obstructive lung disease, cardiac, hepatic and/or renal disease, malignancy, immunodeficiency, and pregnancy as key risk factors for the progression of COVID-19 to severe, i.e., critical disease [ 27 ]. In particular, the presence of any iatrogenic and/or “acquired” immunosuppression (as in injury-associated immunosuppression [ 28 ]) may be important in the context of disease progression [ [29] , [30] , [31] , [32] , [33] , [34] ] and we could recently demonstrate that e.g., cellular immunosuppression of first in line key immune cells can be observed in severe, but not in nonsevere cases [ 35 ].…”

“…In CARDS, however, a classic “cytokine storm” (when compared with bacterial septic shock) is typically not observed [ 55 ] and cytokine levels (including IL-6) are mostly only moderately increased [ 56 ]. However, comparable to severe bacterial infections that lead to critical illness [ 28 , 57 , 58 ], persistent deactivation of key immune cells can be observed in severe COVID-19 as evidenced by e.g., reduced surface expression of the monocytic human leukocyte antigen-DR (mHLA-DR) [ [33] , [34] , [35] ]. This immunosuppression of key immune cells may be important, and it seems tempting to speculate that “injury-associated immunosuppression” might contribute to increased viral replication and overall disease progression [ 35 ].…”

“…Although more data are needed, individuals are all exposed to and infected by the same virus and it appears that individuals with low to mild symptoms mount an effective immune response, while patients with severe symptoms may have a dysfunctional immune reaction, which could promote disease exacerbation and uncontrolled virus replication/expansion [ 29 , [33] , [34] , [35] ]. Potential genetic factors involved in the development of immune response in COVID-19 were proposed and investigated.…”

Potential role for interferon gamma in the treatment of recurrent ventilator-acquired pneumonia in patients with COVID-19: a hypothesis

“…Monocyte deactivation, as assessed by decreased monocytic HLA-DR (mHLA-DR) expression, has been associated with increased risks of intensive care unit (ICU)-acquired infections in various conditions including bacterial sepsis, acute respiratory distress syndrome or trauma [3]. In patients with COVID-19-related pneumonia, decreased mHLA-DR expression is associated with the development of severe respiratory failure, and presumably may contribute to pronounced susceptibility to bacterial superinfections [4,5].…”