Abstract
BackgroundLymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity.ObjectiveWe investigated neutrophil subsets and functions in blood and bronchoalveolar lavage (BAL) of COVID-19 patients on the basis of patients’ clinical characteristics.MethodsWe used a multiparametric cytometry profiling based to mature and immature neutrophil markers in 146 critical or severe COVID-19 patients.ResultsThe Discovery study (38 patients, first pandemic wave) showed that 80% of Intensive Care Unit (ICU) patients develop strong myelemia with CD10−CD64+ immature neutrophils (ImNs). Cellular profiling revealed three distinct neutrophil subsets expressing either the lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), the interleukin-3 receptor alpha (CD123), or programmed death-ligand 1 (PD-L1) overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1- or CD123-expressing ImNs is positively correlated with clinical severity, cytokine storm (IL-1β, IL-6, IL-8, TNFα), acute respiratory distress syndrome (ARDS), and thrombosis. BALs of patients with ARDS were highly enriched in LOX-1-expressing ImN subsets and in antimicrobial neutrophil factors. A validation study (118 patients, second pandemic wave) confirmed and strengthened the association of the proportion of ImN subsets with disease severity, invasive ventilation, and death. Only high proportions of LOX-1-expressing ImNs remained strongly associated with a high risk of severe thrombosis independently of the plasma antimicrobial neutrophil factors, suggesting an independent association of ImN markers with their functions.ConclusionLOX-1-expressing ImNs may help identifying COVID-19 patients at high risk of severity and thrombosis complications.
Highlights
Since the first reports of an outbreak of a severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) in China in December 2019 [1, 2], the coronavirus disease (COVID-19) has grown to be a global public health emergency, with cases of COVID-19 around the world reaching 5.5 million and deaths from the disease standing at more than 90 000 as of May 2021
We designed a first discovery study with 38 individuals and analyzed their neutrophil phenotypes, comparing them with those of patients admitted to the ICU (n = 24) or not (n = 14), within the first day following their admission to the ICU or hospitalization units
Neutrophils from ICU patients were organized in the upper left quadrant of the map, whereas those from the non-ICU patients ended up in the upper right quadrant
Summary
Since the first reports of an outbreak of a severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) in China in December 2019 [1, 2], the coronavirus disease (COVID-19) has grown to be a global public health emergency, with cases of COVID-19 around the world reaching 5.5 million and deaths from the disease standing at more than 90 000 as of May 2021 (for up-to-date data, see https://www.who.int/emergencies/diseases/ novel-coronavirus-2019/situation-reports). Some severe cases of COVID-19 progress to acute respiratory distress syndrome (ARDS), which accounts for high mortality related to damage of the alveolar lumen. The cytokine storm is an uncontrollable inflammatory response leading to viral sepsis, ARDS, respiratory failure, shock, organ failure, or death [7, 8]. Lymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity
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