OC 05.3 - Hypoxia promotes metabolic and functional platelet exhaustion in critically ill COVID-19 patients

Saturday, July 9, 2022

1:30 PM – 1:45 PM

Location: ICC Capital Suite Room 8&9

Presentation Format: In-Person

Co-Author(s)

Ll

Ludovica lombardi

PhD student
Sapienza University of Rome
Rome, Lazio, Italy
FM

Francesca Maiorca

Post-doc
Sapienza University of Rome
Rome, Lazio, Italy
RM

Ramona Marrapodi

Post-doc
Sapienza University of Rome
Roma, Lazio, Italy
NS

Noemi Scafa

undergraduate student
Sapienza University of Rome
Roma, Lazio, Italy
SC

Simone Cesaroni

undergraduate student
Sapienza University of Rome
roma, Lazio, Italy
BC

Bernadette Corica

MD
Sapienza University of Rome
Roma, Lazio, Italy
GR

Giulio F Romiti

MD
Sapienza University of Rome
roma, Lazio, Italy
PP

Patrizia Pasculli

medical resident
Sapienza University of Rome
roma, Lazio, Italy
MC

Maria Rosa Ciardi

full professor
Sapienza University of Rome
Rome, Lazio, Italy
FR

Franco Ruberto

professor
sapienza university of rome
roma, Lazio, Italy
FP

Francesco Pugliese

Full professor
Sapienza university of Rome
Rome, Lazio, Italy
FP

Fabio M. Pulcinelli

Professor
Sapienza University of Rome
Rome, Lazio, Italy
CM

Claudio Mastroianni

full professor
Sapienza University of Rome
Rome, Lazio, Italy
SB

Stefania Basili

MD-PhD
Sapienza University of Rome
roma, Lazio, Italy

Presenting Author(s)

Lucia Stefanini, PhD

Associate Professor
Sapienza University of Rome
Rome, Lazio, Italy

Background: Severe Coronavirus disease 2019 (COVID-19) has been associated with a dysregulated cytokine production, lymphocyte and monocyte exhaustion, and immunothrombotic complications that reduce gas exchange in the lungs and contribute to multiorgan failure.

Aims: The objective of this study was to characterize the interplay between platelets and the dysregulated immune phenotype that drives disease severity.

Methods: To achieve this goal, we performed a high-throughput flow cytometric profiling of the phenotype and interactions of platelets circulating in the blood of Sars-COV2-positive subjects upon hospitalization. Patients were stratified into non-ICU (n=35) and critically ill ICU (n=25) patients and compared to sex- and age-matched Sars-COV2-negative patients (n=15) and healthy volunteers (n=20). All participants gave written informed consent. The study was approved by the Ethics Committee of our institution.

Results: Platelets from ICU patients had dysfunctional mitochondria and a non-adhesive phenotype. Displayed significantly less glycoprotein (GP)Ibalpha and GPVI on the surface and failed to present active integrin alphaIIbbeta3 and P-selectin on the plasma membrane in response to exogenous stimuli. Platelet hypo-responsiveness positively correlated with the Horowitz index (PaO2/FiO2 ratio), a measure of lung function, and with the D-dimer concentration, a surrogate marker of ongoing thrombosis. Exposure of platelets from healthy volunteers to acute hypoxic conditions (1% O2) recapitulated this phenotype in vitro. Despite the low adhesiveness, platelets of ICU patients bound avidly to innate immune cells. Interactions with monocytes and NK cells increased with severity, even though these leukocytes subpopulations were reduced in the circulation of ICU patients. Platelet-T cell aggregates were doubled in non-ICU patients compared to controls but were not detectable among the ICU patients.

Conclusion(s): In summary, platelets from COVID-19 patients who have reduced lung function present features of metabolic and functional exhaustion and bind primarily innate but not adaptive immune cells, thus promoting the dysregulated immune response that drives COVID19 severity.