Platelets and renal failure in the SARS-CoV-2 syndrome

Abstract

The coronavirus disease 19 (COVID-19) is a highly transmittable viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes metallocarboxyl peptidase angiotensin receptor (ACE) 2 to gain entry into human cells. Activation of several proteases facilitates the interaction of viral spike proteins (S1) and ACE2 receptor. This leads to cleavage of host ACE2 receptors. ACE2 activity counterbalances the angiotensin II effect, its loss may lead to elevated angiotensin II levels with modulation of platelet function, size and activity. COVID-19 disease encompasses a spectrum of systemic involvement far beyond respiratory failure alone. Several features of this disease, including the etiology of acute kidney injury (AKI) and the hypercoagulable state, remain poorly understood. Here, we show that there is a high incidence of AKI (81%) in the critically ill adults with COVID-19 in the setting of elevated D-dimer, elevated ferritin, C reactive protein (CRP) and lactate dehydrogenase (LDH) levels. Strikingly, there were unique features of platelets in these patients, including larger, more granular platelets and a higher mean platelet volume (MPV). There was a significant correlation between measured D-dimer levels and MVP; but a negative correlation between MPV and glomerular filtration rates (GFR) in critically ill cohort. Our data suggest that activated platelets may play a role in renal failure and possibly hypercoagulability status in COVID19 patients.

Platelets in the perspective of COVID-19; pathophysiology of thrombocytopenia and its implication as prognostic and therapeutic opportunity

“… [54] 81 M: 60 49 USA This study found increased IPF (greater than7) in COVID-19-infected subjects who had evidence of elevated D-dimers and AKI. [53] Increased P-selectin level Non-severe: 20 Severe: 34 M: 69 M: 59 65 62 Ireland Circulating levels of soluble P-selectin increased in COVID-19 patients compared to the control cohorts and intriguingly, could differentiate between non-severe and severe COVID-19 cohorts. [5] Non-severe: 71 Severe: 44 M: 48 M: 64 54.92 59 Canada Platelet activation, assessed by surface expression of P-selectin and CD63, was evident in patients with severe COVID-19 and strongly correlated with levels of D-dimers.…”

“… [52] 81 M: 60 49 USA There was a significant correlation between D-dimer levels and MVP; but a negative correlation between MPV and GFR in critically ill cohort. [53] IPF 47 M: 56 59.6 Israel Patients with COVID-19 have increased IPF compared to stable patients with cardiovascular risk factors, suggesting that the enhanced platelet turnover may have a role in the development of thrombotic events in COVID-19 patients. [27] 982 M: 71 68 Europa IPF tended to increase with disease severity.…”

Pathophysiology of COVID-19-associated acute kidney injury

“…SARS-CoV-2 has furthermore been shown to bind to platelets via ACE2, leading to platelet activation and immunothrombosis 64 – 66 . Thus, platelet activation may represent a potential player in the pathophysiology of COVID-19 AKI 67 , 68 . Circulating prothrombotic autoantibodies that target phospholipids and phospholipid-binding proteins have also been reported 69 .…”

Mean Platelet Volume Predicts Severe COVID-19 Illness

“…A total number of 18 studies were finally included in our analysis, with 3,433 COVID-19 patients, 780 (22.7%) with severe illness (►Table 1). [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] All except two were crosssectional studies, with the majority from China (7; 39%), and used heterogeneous combination of clinical endpoints for defining severity of COVID-19 (44% included respiratory failure and/or intensive care unit admission, 33% death, and 6% acute kidney failure or thrombosis; ►Table 1).…”