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Platelets are central elements of hemostasis and also play a pivotal role in the pathogenesis of thrombosis in coronavirus disease 2019. This study was planned to investigate the effects of different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant spike protein variants on platelet morphology and activation. Citrated whole blood collected from ostensibly healthy subjects was challenged with saline (control sample) and with 2 and 20 ng/mL final concentration of SARS-CoV-2 recombinant spike protein of Ancestral, Alpha, Delta, and Omicron variants. Platelet count was found to be decreased with all SARS-CoV-2 recombinant spike protein variants and concentrations tested, achieving the lowest values with 20 ng/mL Delta recombinant spike protein. The mean platelet volume increased in all samples irrespective of SARS-CoV-2 recombinant spike protein variants and concentrations tested, but especially using Delta and Alpha recombinant spike proteins. The values of both platelet function analyzer-200 collagen-adenosine diphosphate and collagen-epinephrine increased in all samples irrespective of SARS-CoV-2 recombinant spike protein variants and concentrations tested, and thus reflecting platelet exhaustion, and displaying again higher increases with Delta and Alpha recombinant spike proteins. Most samples where SARS-CoV-2 recombinant spike proteins were added were flagged as containing platelet clumps. Morphological analysis revealed the presence of a considerable number of activated platelets, platelet clumps, platelet-monocyte, and platelet-neutrophils aggregates, especially in samples spiked with Alpha and Delta recombinant spike proteins at 20 ng/mL. These results provide support to the evidence that SARS-CoV-2 is capable of activating platelets through its spike protein, though such effect varies depending on different spike protein variants. [ABSTRACT FROM AUTHOR]

Although the worldwide usage of direct oral anticoagulants has continuously increased over the past decade, heparin remains an important weapon in the current arsenal of anticoagulant drugs. Parenteral heparin administration (i.e., either intravenously or subcutaneously) has represented for decades the only possible route for generating a significant anticoagulant effect, although being notoriously associated with some important drawbacks such as discomfort and risk of low compliance, thus paving the way to searching for more amenable means of administration. We provide here an updated analysis of animal and human studies that have explored the feasibility, suitability, and efficiency of heparin administration through the unconventional nasal route, as a possible alternative to the more traditional parenteral injection. The major hurdles that contribute to impair intranasal absorption and systemic delivery of heparin are represented by its relatively high molecular weight and negative charge. Therefore, although pure drug administration would not be associated with efficient nasal adsorption, or by systemic biological activity (i.e., anticoagulant effect), the combination of low molecular weight heparins and absorption enhancers such as surfactants, mucoadhesive, cyclodextrins, polyethylenimines and encapsulation into (nano)carriers seems effective to at least partially improve drug transport through the nasal route and allow systemic delivery in animals. Besides generating anticoagulant effects, intranasal heparin administration can also produce local pleiotropic effects, mostly related to anti-inflammatory properties, such as attenuating airway allergic inflammation or inhibiting the binding of the spike protein of some coronaviruses (including severe acute respiratory syndrome coronavirus 2) to their host cell receptors. This preliminary evidence represents a valuable premise for planning future studies in humans aimed at establishing the pharmacokinetics and biological activity of locally and systemically delivered intranasal heparin formulations. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a life-threatening infectious disorder characterized by a sustained prothrombotic state. Since homocysteine is a potential biomarker of thrombotic diseases, the aim of this article is to provide an updated overview on the possible role played by hyperhomocysteinemia in influencing an unfavorable COVID-19 progression. We carried out an electronic search in Medline (PubMed interface) using the keywords ("COVID-19" OR "SARS-CoV-2") AND "homocysteine", between 2019 and the present time, with no language restrictions, to identify all articles which explored the concentration of homocysteine in COVID-19 patients with or without unfavorable disease progression. Three studies, totaling 694 hospitalized COVID-19 patients, were included in our systematic review. Overall, the differences between the mean homocysteine values in non-severe vs. severe COVID-19 patients were always positive (i.e., 15.1%, 24.1% and 22.8%, generating a positive weight mean difference of 1.75 μmol/L (95%CI, 1.26–2.25 μmol/L; p=0.011), which translates into a cumulative difference of approximately ∼1.2 μmol/L. Despite the limited evidence that has been garnered so far, increased homocysteine ​​levels may be a potentially useful marker for predicting the risk of unfavorable progression in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Here we report the results of a systematic review aimed at exploring the possible association between increased blood lactate levels, disease severity and mortality in COVID-19 patients, including a comparison of lactate values between COVID-19 and non-COVID-19 patients. Keywords: COVID-19; lactate; lactic acid; SARS-CoV-2; systematic literature review EN COVID-19 lactate lactic acid SARS-CoV-2 systematic literature review 332 337 6 02/07/22 20220201 NES 220201 Introduction Coronavirus disease 2019 (COVID-19), a new life-threatening infectious pathology caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is generating dramatic clinical impacts worldwide, with substantial derangements in the organization of healthcare, society and economy. It is important to underpin that most COVID-19 patients in the studies included in our analysis did not have baseline hyperlactatemia and that substantially elevated blood lactate values were often absent in many COVID-19 patients who developed unfavourable clinical outcomes (Tables 1-3). This hypothesis is confirmed by evidence that patients with COVID-19 pneumonia or ARDS present with lower blood lactate values compared to those with non-COVID-19 pneumonia or ARDS of different aetiologies (Table 4). [Extracted from the article]

The worldwide spread of coronavirus disease 2019 (COVID-19) has generated a global health crisis and more than a million deaths so far. Epidemiological and clinical characteristics of COVID-19 are increasingly reported, along with its potential relationship with overweight and/or obesity. Therefore, we aim here to review the current scientific literature on the impact of overweight and/or obesity among hospitalized patients who have developed severe or critical forms of COVID-19. Following PRISMA guidelines, our literature search identified over 300 scientific articles using the keywords "obesity" and "COVID-19", 22 of which were finally selected for reporting useful information on the association between overweight/obesity and disease severity. In particular, in 11 out of the 14 studies (79%) which evaluated the association between obesity and disease severity providing also a risk estimate (i.e., the odd ratio; OR), the OR value was constantly >2. Although the studies were found to be heterogeneous in terms of design, population, sample size and endpoints, in most cases a significant association was found between obesity and the risk of progressing to severe COVID-19 illness, intensive care unit admission and/or death. We can hence conclude that an increased body mass index shall be considered a negative prognostic factor in patients with COVID-19, and more aggressive prevention or treatment shall hence be reserved to overweight and/or obese patients. [ABSTRACT FROM AUTHOR]

Because there is little published evidence on the effects of incomplete filling of K2EDTA evacuated blood tubes on routine hematological testing, this original study aimed to provide updated information on this preanalytical aspect. The study population consisted of 17 ostensibly healthy volunteers. Blood was drawn by venipuncture with a 10 mL syringe and dispensed in varying amounts (0.2, 0.5, 1.0, 2.0, and 3.0 mL) into 3.0 mL blood tubes containing spray-dried 5.4 mg K2EDTA. All tubes were gently mixed and used to perform routine hematology tests on the Sysmex XN-10. Clinically significant variations were defined when the limits of desirable specifications of bias derived from biologic variation were exceeded. The desirable bias was exceeded in 33 % filled tubes (1.0 mL) for hematocrit and MCV (increased values) and for MCHC (decreased values), while it was exceeded in 17 % filled tubes (0.5 mL) for hemoglobin, hematocrit and MCV (increased values), and for MCHC (decreased values). Finally, the variation of values was higher than the desirable bias for RBC, hemoglobin, hematocrit and MCV (increase), and for MCHC and MPV (decrease) in 7 % filled tubes (0.2 mL). No clinically significant variations were observed in tubes filled up to 67 % of their nominal volume (i.e., 2.0 mL). Consideration should be given to reject spray-dried K2EDTA blood tubes that contain a blood volume <67 % of the nominal fill volume, as biased laboratory data in these samples may interfere with clinical decision making and care management. [ABSTRACT FROM AUTHOR]

This study investigated the biological effects on circulating monocytes after challenge with SARS-CoV-2 recombinant spike protein. Whole blood collected from seven ostensibly healthy healthcare workers was incubated for 15 min with 2 and 20 ng/mL final concentration of recombinant spike protein of Ancestral, Alpha, Delta, and Omicron variants. Samples were analyzed with Sysmex XN and DI-60 analyzers. Cellular complexity (i.e., the presence of granules, vacuoles and other cytoplasmic inclusions) increased in all samples challenged with the recombinant spike protein of the Ancestral, Alpha, and Delta variants, but not in those containing Omicron. The cellular content of nucleic acids was constantly decreased in most samples, achieving statistical significance in those containing 20 ng/mL of Alpha and Delta recombinant spike proteins. The heterogeneity of monocyte volumes significantly increased in all samples, achieving statistical significance in those containing 20 ng/mL of recombinant spike protein of the Ancestral, Alpha and Delta variants. The monocyte morphological abnormalities after spike protein challenge included dysmorphia, granulation, intense vacuolization, platelet phagocytosis, development of aberrant nuclei, and cytoplasmic extrusions. The SARS-CoV-2 spike protein triggers important monocyte morphological abnormalities, more evident in cells challenged with recombinant spike protein of the more clinically severe Alpha and Delta variants. [ABSTRACT FROM AUTHOR]