Abstract
Cytokine storm–mediated organ injury continues to dominate current thinking as the primary mechanism for coronavirus disease 2019 (COVID-19). Although there is an initial hyper-inflammatory phase, mounting evidence suggests that virus-induced defective host immunity may be the real cause of death in many patients.1,2 COVID-19 has been called a serial lymphocyte killer because profound and protracted lymphopenia is a near uniform finding among patients with severe COVID-19 and correlates with morbidity and mortality.1,3 Autopsies demonstrate a devastating depletion of lymphocytes in the spleen and other organs.2 CD4, CD8, and natural killer cells, which play important antiviral roles, are depleted and have reduced function, leading to immune collapse.1 Clinical and pathological findings in patients with COVID-19 indicate that immunosuppression is a critical determinant of outcomes. Secondary hospital-acquired infections occur in 50% of patients who die.1 Cell inclusion bodies, consistent with viral persistence, have been found in lungs, kidneys, and other organs.1,2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific quantitative polymerase chain reaction has revealed viral load in the lungs of most patients at autopsy, consistent with an inability to eliminate the pathogen.1,2 Collectively, these studies indicate that impaired immune competence is an important pathogenic mechanism in COVID-19. Interleukin 7 (IL-7) is a pleiotropic cytokine essential for lymphocyte survival and expansion.4,5 Administration of IL-7 invariably increases circulating and tissue lymphocytes and has been administered to more than 450 patients with an excellent safety profile.4,5 IL-7 is currently in multiple randomized clinical trials for oncologic and infectious disorders, and a trial in the United Kingdom is evaluating its use among patients with severe COVID-19. Importantly, IL-7 has documented efficacy as an antiviral agent.4,5 IL-7 therapy has been shown to restore lymphocyte counts and functional activity, leading to decreased viral load and clinical improvement in several life-threating viral infections.4,5 It has been shown to increase CD4 and CD8 T-cells 3-fold, to improve T-cell activation, to not increase proinflammatory cytokines, and to be well tolerated in patients with bacterial sepsis.6 Thus, a compelling scientific rationale exists for examining whether IL-7 is associated with restored host protective immunity in patients with COVID-19 and immunosuppression and improve outcomes.1
Highlights
Cytokine storm–mediated organ injury continues to dominate current thinking as the primary mechanism for coronavirus disease 2019 (COVID-19)
Interleukin 7 (IL-7) was approved by the Ethics Committee of St Luc University Hospital (Brussels, Belgium) for compassionate use in 12 critically ill patients with COVID-19 and severe lymphopenia who had 2 consecutive absolute lymphocyte counts of less than 700/μL
No observed treatment-associated adverse effects were noted, and IL-7 was well tolerated without inducing changes in temperature, blood pressure, or PaO2:FiO2 ratio (Figure)
Summary
Cytokine storm–mediated organ injury continues to dominate current thinking as the primary mechanism for coronavirus disease 2019 (COVID-19). COVID-19 has been called a serial lymphocyte killer because profound and protracted lymphopenia is a near uniform finding among patients with severe COVID-19 and correlates with morbidity and mortality.[1,3] Autopsies demonstrate a devastating depletion of lymphocytes in the spleen and other organs.[2] CD4, CD8, and natural killer cells, which play important antiviral roles, are depleted and have reduced function, leading to immune collapse.[1]. Secondary hospital-acquired infections occur in 50% of patients who die.[1] Cell inclusion bodies, consistent with viral persistence, have been found in lungs, kidneys, and other organs.[1,2] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific quantitative polymerase chain reaction has revealed viral load in the lungs of most patients at autopsy, consistent with an inability to eliminate the pathogen.[1,2] Collectively, these studies indicate that impaired immune competence is an important pathogenic mechanism in COVID-19
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