ABSTRACT
OBJECTIVE: The aim of the study was to determine the association between platelet indices and disease severity, and outcomes of the patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a secondary hospital. PATIENTS AND METHODS: 722 hospitalized patients who had positive rRT-PCR for SARS-CoV-2 and/or typical findings of COVID-19 at chest computed tomography (CT) were enrolled in this study. Initial platelet count (PLT) and indices, including mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), MPV/PCT, MPV/PLT, PDW/PLT, PDW/PCT on admission and the third day of hospitalization, and their relationship with disease severity and outcomes were evaluated retrospectively. RESULTS: The mean age of the patients was 57.2±15.6 years (range: 16-94) and male/female ratio was 1.22. 81.9% of the patients had moderate and 11.8% had severe disease. 1.8% of the patients had thrombocytopenia at admission. The patients transferred to the intensive care unit (ICU) had significantly lower baseline lymphocyte counts, PLT, PCT, and 3rd day lymphocyte counts when compared with the patients in wards. ICU patients also had higher baseline CRP, LDH, ferritin, MPV/PCT, MPV/PLT, PDW/PLT, PDW/PCT ratios, and 3rd day PDW, CRP, LDH, and ferritin levels than the patients in wards. Mortality was associated with lower baseline lymphocyte counts, PLT, PCT, 3rd day lymphocyte counts and PCT. Higher baseline CRP, LDH, ferritin, MPV/PCT, PDW/PLT, PDW/PCT and 3rd day CRP, LDH, ferritin, procalcitonin, PDW, MPV/PCT, PDW/PLT, and PDW/PCT ratios were also associated with poor prognosis. CONCLUSIONS: Platelet count and ratios were significantly associated with mortality in patients with COVID-19.
Subject(s)
Blood Platelets/cytology , COVID-19/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Area Under Curve , COVID-19/mortality , COVID-19/virology , Female , Humans , Intensive Care Units , Male , Middle Aged , Platelet Count , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Survival Analysis , Young AdultABSTRACT
Of the two known apical isoforms of the Na(+)/H(+) exchanger (NHE) family, only the NHE3 gene is regulated by glucocorticoids. The aim of these studies was to investigate the mechanisms underlying the effects of methylprednisolone (MP) on expression of NHE3 in the proximal and distal small intestine of suckling and adult rats. Immunoblots showed that the glucocorticoid responsiveness in the proximal small intestine was greatest in suckling animals (NHE3/beta-actin: 0.43 +/- 0.09 control vs. 1.57 +/- 0.15 MP; P < 0. 001), and responsiveness decreased with age with no effect in adults (0.56 +/- 0.14 vs. 0.64 +/- 0.17). Distal small intestine was responsive only in adult rats (0.49 +/- 0.13 vs. 1.65 +/- 0.09; P < 0.001). This pattern was confirmed at the mRNA level and by (22)Na(+) uptake. Western blot and [(3)H]dexamethasone mesylate binding showed that the responsiveness of NHE3 to glucocorticoids is directly related to the expression of glucocorticoid receptor (GR) in the small intestine. These studies suggest that loss and gain of glucocorticoid responsiveness in the proximal and distal small intestine, respectively, are related to age- and segment-dependent expression of GR.
Subject(s)
Aging/metabolism , Glucocorticoids/pharmacology , Intestine, Small/metabolism , Methylprednisolone/pharmacology , Sodium-Hydrogen Exchangers/metabolism , Animals , Animals, Suckling/metabolism , Blotting, Northern , Blotting, Western , Child, Preschool , Dexamethasone/analogs & derivatives , Dexamethasone/metabolism , Humans , Male , Microvilli/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Glucocorticoid/metabolism , Sodium-Hydrogen Exchanger 3 , Sodium-Hydrogen Exchangers/genetics , Tissue DistributionABSTRACT
The effects of chronic administration of methylprednisolone (MP) were studied on the ontogeny of the renal type II Na-P(i) transporter (NaPi-2). Immunoblot analysis showed that MP did not alter the expression of NaPi-2 protein levels in suckling and weanling rats; however, there was an approximately 50% decrease in adolescent and adult rats. There was no change in Na-dependent P(i) uptake in brush-border membrane vesicles in suckling rats, but there was an almost twofold decrease in adolescent rats induced by MP treatment. MP administration did not alter mRNA levels in suckling or adolescent rats. Dual injections with the glucocorticoid receptor blocker RU-486 (mifepristone) and MP did not reverse the downregulation of NaPi-2 immunoreactive protein levels in adolescent rats. To control for RU-486 antagonism efficiency, Na/H exchanger isoform 3 (NHE3) protein levels were also assayed after injection with RU-486 and MP. As expected, NHE3 protein levels increased after MP injection; however, the increase was blocked in adolescent rats by RU-486. We conclude that there is an age-dependent responsiveness to glucocorticoids and that the marked decrease in NaPi-2 immunoreactive protein levels and activity in adolescent rats is due to posttranscriptional mechanisms.
