ABSTRACT
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. Aim(s): The objective of this study was to characterize the interplay between platelets and the dysregulated immune phenotype that drives disease severity. Method(s): 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. Result(s): 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.
ABSTRACT
BACKGROUND: Little is known in distinguishing clinical features and outcomes between coronavirus disease-19 (COVID-19) and influenza (FLU). MATERIALS/METHODS: Retrospective, single-centre study including patients with COVID-19 or FLU pneumonia admitted to the Intensive care Unit (ICU) of Policlinico Umberto I (Rome). Aims were: (1) to assess clinical features and differences of patients with COVID-19 and FLU, (2) to identify clinical and/or laboratory factors associated with FLU or COVID-19 and (3) to evaluate 30-day mortality, bacterial superinfections, thrombotic events and invasive pulmonary aspergillosis (IPA) in patients with FLU versus COVID-19. RESULTS: Overall, 74 patients were included (19, 25.7%, FLU and 55, 74.3%, COVID-19), median age 67 years (58-76). COVID-19 patients were more male (p = 0.013), with a lower percentage of COPD (Chronic Obstructive Pulmonary Disease) and chronic kidney disease (CKD) (p = 0.001 and p = 0.037, respectively) than FLU. SOFA score was higher (p = 0.020) and lymphocytes were significantly lower in FLU than in COVID-19 [395.5 vs 770.0 cells/mmc, p = 0.005]. At multivariable analysis, male sex (OR 6.1, p < 0.002), age > 65 years (OR 2.4, p = 0.024) and lymphocyte count > 725 cells/mmc at ICU admission (OR 5.1, p = 0.024) were significantly associated with COVID-19, whereas CKD and COPD were associated with FLU (OR 0.1 and OR 0.16, p = 0.020 and p < 0.001, respectively). No differences in mortality, bacterial superinfections and thrombotic events were observed, whereas IPA was mostly associated with FLU (31.5% vs 3.6%, p = 0.0029). CONCLUSIONS: In critically ill patients, male sex, age > 65 years and lymphocytes > 725 cells/mmc are related to COVID-19. FLU is associated with a significantly higher risk of IPA than COVID-19.