Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman-Diamond syndrome cells.

Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency and skeletal abnormalities. SDS bone marrow haematopoietic progenitors show increased apoptosis and impairment in granulocytic differentiation. Loss of Shwachman-Bodian-Diamond syndrome (SBDS) expression results in reduced eukaryotic 80S ribosome maturation. Biallelic mutations in the SBDS gene are found in ~90% of SDS patients, ~55% of whom carry the c.183-184TA>CT nonsense mutation. Several translational readthrough-inducing drugs aimed at suppressing nonsense mutations have been developed. One of these, ataluren, has received approval in Europe for the treatment of Duchenne muscular dystrophy. We previously showed that ataluren can restore full-length SBDS protein synthesis in SDS-derived bone marrow cells. Here, we extend our preclinical study to assess the functional restoration of SBDS capabilities in vitro and ex vivo. Ataluren improved 80S ribosome assembly and total protein synthesis in SDS-derived cells, restored myelopoiesis in myeloid progenitors, improved neutrophil chemotaxis in vitro and reduced neutrophil dysplastic markers ex vivo. Ataluren also restored full-length SBDS synthesis in primary osteoblasts, suggesting that its beneficial role may go beyond the myeloid compartment. Altogether, our results strengthened the rationale for a Phase I/II clinical trial of ataluren in SDS patients who harbour the nonsense mutation.

Epidemiology and Predisposing Factors of Post-COVID Venous Thrombosis: A Concise Review.

Long-coronavirus disease 2019 (COVID-19) represents a heterogeneous clinical syndrome characterized by a pathologic continuum of signs, symptoms, and also laboratory/radiologic abnormalities that may persist for a long time after recovering from an acute severe acute respiratory syndrome-coronavirus disease 2 infection. Among the various components of this postviral condition, the risk of venous thromboembolism in patients hospitalized for COVID-19 remains considerably higher after discharge, especially in older individuals, in men, in patients with longer hospital stays and more aggressive treatment (e.g., mechanical ventilation and/or intensive care), when thromboprophylaxis is not used, and in those with a persistent prothrombotic state. Patients who have these predisposing factors should be monitored more closely to intercept any thrombosis that may occur in a post-COVID time-related manner but may also benefit from extended thromboprophylaxis and/or antiplatelet therapy.

Pearls and Pitfalls in the Measurement of Direct Oral Anticoagulants.

Due to their widespread use, testing for direct oral anticoagulants (DOACs) has become urgent in certain clinical situations. Screening based on widely available, rapid, and simple hemostasis assays such as prothrombin time, activated partial thromboplastin time, or even diluted Russel Viper venom time may provide sufficient evidence of "over-coagulation" and could be used "in small/peripheral/spoke laboratories" as an emergency strategy, but is not thought to be reliable for driving clinical decision making. Given their good correlation with plasma concentration, urine dipsticks may be considered a valuable alternative for emergency screening, although their performance is dependent on renal function, may vary depending on the time since the last urination, and there may be problems of interfacing with the laboratory/hospital information system. Separation methods based on liquid chromatography and mass spectrometry may be clinically questionable, since they measure the concentration rather than the actual inhibitory effect of DOACs, are relatively expensive, cumbersome and time consuming, and therefore seem unsuitable for most conditions requiring urgent clinical decision making. A proposed approach therefore involves establishing a network of routine clinical laboratories, designating a reference center where DOAC tests could be available 24/7, establishing a clear diagnostic care pathway for ordering the tests from the laboratory and standard operating procedures for performing them, the use of the diluted thrombin time for dabigatran and anti-FXa assays (drug-calibrated) for rivaroxaban, apixaban, and edoxaban, as well as providing expert advice throughout the testing process, from ordering to interpretation of results.

Are Antiphospholipid Antibodies a Surrogate Risk Factor for Thrombosis in Sepsis?

Antiphospholipid syndrome (APS) is a hypercoagulable state caused by antiphospholipid antibodies (aPL). APS clinically manifests with arterial or venous or microvascular thrombi and/or pregnancy complications. It is well-known that the development of aPL can be a transient phenomenon and thus the current diagnostic criterion for APS requires repeat laboratory testing several weeks apart before a definitive diagnosis is made. However, transient presence of aPL may also be pathogenic. In this article, we attempt to give historical and clinical evidence for the importance of these antibodies, even when transient, and call for further research into mechanisms by which these antibodies may promote thrombosis and pregnancy morbidities.

Laboratory Testing for ADAMTS13 for Thrombotic Thrombocytopenia Purpura and Beyond.

ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), also called von Willebrand factor (VWF) cleaving protease, acts as a moderator of VWF activity. ADAMTS13 cleaves VWF multimers, thereby reducing VWF activity in blood. When ADAMTS13 is absent (e.g., in patients with TTP [thrombotic thrombocytopenia purpura]), accumulation of VWF in plasma can occur, particularly as "ultra-large" VWF multimers, with this leading to adverse outcomes such as thrombosis. Relative ADAMTS13 deficiencies also occur in several other conditions, including secondary thrombotic microangiopathies (TMA), cancer, and with severe infections such as in COVID-19 (coronavirus disease 2019). These situations might therefore be accompanied with relative loss of ADAMTS13, thereby potentially also leading to pathological VWF accumulation, with this then generating a prothrombotic milieu, thus contributing to enhance the risk of thrombosis. Laboratory testing for ADAMTS13 can aid in the diagnosis of such disorders (i.e., TTP, TMA), and help guide their management, with testing now accomplished using various assays. As most presentations of TTP reflect an acquired condition due to anti-ADAMTS13 antibodies, there may also be a need to test for these, as this will also influence clinical management. We herein provide an overview of TTP, note other conditions in which low levels of ADAMTS13 may be present, and then detail laboratory testing for both ADAMTS13 and associated inhibitors.

Venous Thrombosis in Airborne Viral Infections: Is Coronavirus Disease 2019 now Any Different from Influenza?

One of the hallmarks of coronavirus disease 2019 (COVID-19), particularly in complicated cases (i.e., requiring hospitalization or intensive care support), is persistent hemostasis activation, which may be associated with a vast array of thrombotic episodes involving both the arterial and venous systems. The renewed emphasis on the relationship between viral infections and venous thrombosis paves the way for determining whether a more common and often underestimated infection disease, such as influenza, may also be associated with a significant burden of venous thrombotic episodes, and how this eventual thrombotic risk compares to that seen in COVID-19, both in the past and with newer variants. Our review of studies comparing the burden of venous thromboembolism (VTE) in patients with COVID-19 or influenza revealed that the thrombotic risk appears to be significantly higher in patients with COVID-19 but remains certainly not meaningless in those with influenza, particularly in subjects infected by highly virulent strains (i.e., H1N1), in those who develop pneumonia and require intensive care support. In these specific clinical settings, the adoption of tailored thromboprophylaxis may be indicated though more studies are compellingly needed on this matter. As COVID-19 variants emerge, there is a possibility that the VTE burden of COVID-19 will decrease, and progress to that of other respiratory viruses.

Hemostasis Testing in the Emergency Department: A Narrative Review.

Routine laboratory screening is typically performed at initial evaluation of the vast majority of presentations to the emergency department (ED). These laboratory results are crucial to the diagnostic process, as they may influence up to 70% of clinical decisions. However, despite the usefulness of biological assessments, many tests performed are inappropriate or of doubtful clinical relevance. This overutilization rate of laboratory testing in hospitals, which represents a significant medical-economic burden, ranges from 20 to 67%, with coagulation tests at the top of the list. While reviews frequently focus on nonintensive care units, there are few published assessments of emergency-specific interventions or guidelines/guidance to date. The aim of this review is to highlight current recommendations for hemostasis evaluation in the emergency setting with a specific analysis of common situations leading to ED admissions, such as suspected venous thrombosis or severe bleeding. We revisit the evidence related to the assessment of patient's hemostatic capacity based on comprehensive history taking and physical examination as well as best practice recommendations for blood sample collection to ensure the reliability of results. This review also includes an examination of various currently available point of care tests and a comprehensive discussion on indications, limitations, and interpretation of these tests.

Effects of Recombinant SARS-CoV-2 Spike Protein Variants on Platelet Morphology and Activation.

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.

Strict regulations on energy drinks to protect Minors' health in Europe - It is never too late to set things right at home.

The consumption of energy drinks poses significant risks to minors' health, and strict regulations are urgently needed to protect them. The high caffeine, high sugar, and high caloric content of energy drinks have drawn concern from health professionals. The consumption of energy drinks has been linked to unhealthy dietary behaviors, obesity, and mental health problems in adolescents. The psychoactive and stimulant effects of energy drinks are particularly worrisome, and the marketing of these drinks on social media platforms is also a cause for alarm. In light of these concerns, we strongly recommend policy measures, such as restrictions on the sale of energy drinks to minors, to prevent their health risks. The evidence clearly suggests that energy drinks pose significant risks to minors' health and well-being, and regulatory standards must be implemented without further delay.

Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review.

PURPOSE: Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if having received pharmacological treatment during acute SARS-CoV-2 infection may reduce the risk of long-COVID. METHODS: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to July 15th, 2023. Articles comparing the presence of long-COVID symptoms between individuals who received or not a specific medication, particularly antivirals, during the acute phase of SARS-CoV-2 infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool. RESULTS: From 517 studies identified, 6 peer-reviewed studies and one preprint met all inclusion criteria. The sample included 2683 (n = 4) hospitalized COVID-19 survivors and 307,409 (n = 3) non-hospitalized patients. The methodological quality was high in 71% of studies (n = 5/7). Two studies investigating the effects of Nirmaltrevir/Ritonavir and three studies the effect of Remdesivir reported conflicting results on effectiveness for preventing long-COVID. Three studies investigating the effects of other medication such as Dexamethasone (n = 2) or Metformin (n = 1) found positive results of these medications for preventing long-COVID. CONCLUSION: Available evidence about the effect of medication treatment with antivirals during acute COVID-19 and reduced risk of developing long-COVID is conflicting. Heterogeneous evidence suggests that Remdesivir or Nirmaltrevir/Ritonavir could have a potential protective effect for long-COVID. A limited number of studies demonstrated a potential benefit of other medications such as Dexamethasone or Metformin, but more studies are needed.

Personalized laboratory medicine in the digital health era: recent developments and future challenges.

Interpretation of laboratory data is a comparative procedure and requires reliable reference data, which are mostly derived from population data but used for individuals in conventional laboratory medicine. Using population data as a "reference" for individuals has generated several problems related to diagnosing, monitoring, and treating single individuals. This issue can be resolved by using data from individuals' repeated samples, as their personal reference, thus needing that laboratory data be personalized. The modern laboratory information system (LIS) can store the results of repeated measurements from millions of individuals. These data can then be analyzed to generate a variety of personalized reference data sets for numerous comparisons. In this manuscript, we redefine the term "personalized laboratory medicine" as the practices based on individual-specific samples and data. These reflect their unique biological characteristics, encompassing omics data, clinical chemistry, endocrinology, hematology, coagulation, and within-person biological variation of all laboratory data. It also includes information about individuals' health behavior, chronotypes, and all statistical algorithms used to make precise decisions. This approach facilitates more accurate diagnosis, monitoring, and treatment of diseases for each individual. Furthermore, we explore recent advancements and future challenges of personalized laboratory medicine in the context of the digital health era.

The impact of physiological variations on personalized reference intervals and decision limits: an in-depth analysis.

The interpretation of laboratory data is a comparative procedure. Physicians typically need reference values to compare patients' laboratory data for clinical decisions. Therefore, establishing reliable reference data is essential for accurate diagnosis and patient monitoring. Human metabolism is a dynamic process. Various types of systematic and random fluctuations in the concentration/activity of biomolecules are observed in response to internal and external factors. In the human body, several biomolecules are under the influence of physiological rhythms and are therefore subject to ultradian, circadian and infradian fluctuations. In addition, most biomolecules are also characterized by random biological variations, which are referred to as biological fluctuations between subjects and within subjects/individuals. In routine practice, reference intervals based on population data are used, which by nature are not designed to capture physiological rhythms and random biological variations. To ensure safe and appropriate interpretation of patient laboratory data, reference intervals should be personalized and estimated using individual data in accordance with systematic and random variations. In this opinion paper, we outline (i) the main variations that contribute to the generation of personalized reference intervals (prRIs), (ii) the theoretical background of prRIs and (iii) propose new methods on how to harmonize prRIs with the systematic and random variations observed in metabolic activity, based on individuals' demography.

Diurnal and day-to-day biological variation of salivary cortisol and cortisone.

OBJECTIVES: There is a growing interest in the relevance of salivary cortisol and cortisone concentrations in stress-related research. To correctly attribute the magnitude of salivary cortisol and cortisone variation as an effect of a stressful event, a coherent understanding of the day-to-day intra-individual and inter-individual variability across the diurnal cycle of the two steroids is required. However, such information is currently lacking. METHODS: This study aimed to overcome these existing limitations by performing an investigation of the biological variation (BV) of salivary cortisol and cortisone within one day and between five days using an LC-MS/MS method. Saliva samples were collected from 20 healthy volunteers immediately after waking up, at 8:00, 12:00, 15:00, 19:00 and 23:00 on each day over five days. All samples were analyzed in duplicate in one run. Nested ANOVA was used to calculate the sums of squares for analytical and biological components of variation. RESULTS: The within-subject BV of salivary cortisol and cortisone (CVI) ranged from a minimum of 29.3 and 19.0 % to a maximum of 56.5 and 49.1 %, respectively, while the between-subject biological variation (CVG) ranged from 29.7 and 29.0 % to 51.6 and 43.6 %. The reference change values (RCVs) ranged from 96 to 245 % for cortisol and from 55 to 194 % for cortisone. A medium index of individuality was observed for both compounds at all time points. CONCLUSIONS: This study provides updated BV estimates and RCVs for different times of day that can be used to assess the magnitude of change in biomarkers in future stress-related research.

Analytical evaluation of the novel Mindray high sensitivity cardiac troponin I immunoassay on CL-1200i.

OBJECTIVES: The current study was designed to evaluate the analytical performance of the new Mindray highly sensitive cardiac troponin I (hs-cTnI) chemiluminescent immunoassay on Mindray CL-1200i, as a thorough validation of novel hs-cTnI methods is required before introduction into clinical practice. METHODS: The evaluation of the analytical performance of this hs-cTnI immunoassay encompassed the calculation of the limit of blank (LOB), limit of detection (LOD), functional sensitivity, imprecision, linearity, 99th percentile upper reference limit (URL) and concordance with another previously validated hs-cTnI chemiluminescent immunoassay. RESULTS: The LOB and LOD were 0.32 and 0.35 ng/L, whilst the functional sensitivity (expressed as cTnI value with <10 % imprecision), was 0.35 ng/L. The linearity was excellent throughout a wide range of clinically measurable values (r=1.00 between 0.8 and 9,726.9 ng/mL). The intra-assay, inter-assay and total imprecision were 1.1-1.3 %, 5.5-8.1 % and 5.6-8.2 %, respectively. The 99th percentile URL calculated using residual plasma from 246 ostensibly healthy blood donors was 9.2 ng/L (4.3 ng/L in women vs. 12.3 ng/L in men). The Spearman's correlation between Mindray hs-cTnI and Access hs-TnI was 0.97, with mean bias of 7.2 % (95 % CI, 2.6-11.9 %). CONCLUSIONS: Although we failed to confirm the very optimistic analytical characteristics previously reported for this method, our evaluation of the novel Mindray hs-cTnI immunoassay on CL-1200i demonstrated that the overall performance is comparable to that of other commercially available hs-cTnI techniques, making it a viable alternative to other methods.

A vision to the future: value-based laboratory medicine.

The ultimate goal of value-based laboratory medicine is maximizing the effectiveness of laboratory tests in improving patient outcomes, optimizing resources and minimizing unnecessary costs. This approach abandons the oversimplified notion of test volume and cost, in favor of emphasizing the clinical utility and quality of diagnostic tests in the clinical decision-making. Several key elements characterize value-based laboratory medicine, which can be summarized in some basic concepts, such as organization of in vitro diagnostics (including appropriateness, integrated diagnostics, networking, remote patient monitoring, disruptive innovations), translation of laboratory data into clinical information and measurable outcomes, sustainability, reimbursement, ethics (e.g., patient empowerment and safety, data protection, analysis of big data, scientific publishing). Education and training are also crucial, along with considerations for the future of the profession, which will be largely influenced by advances in automation, information technology, artificial intelligence, and regulations concerning in vitro diagnostics. This collective opinion paper, composed of summaries from presentations given at the two-day European Federation of Laboratory Medicine (EFLM) Strategic Conference "A vision to the future: value-based laboratory medicine" (Padova, Italy; September 23-24, 2024), aims to provide a comprehensive overview of value-based laboratory medicine, projecting the profession into a more clinically effective and sustainable future.

Point-of-care testing: state-of-the art and perspectives.

Point-of-care testing (POCT) is becoming an increasingly popular way to perform laboratory tests closer to the patient. This option has several recognized advantages, such as accessibility, portability, speed, convenience, ease of use, ever-growing test panels, lower cumulative healthcare costs when used within appropriate clinical pathways, better patient empowerment and engagement, and reduction of certain pre-analytical errors, especially those related to specimen transportation. On the other hand, POCT also poses some limitations and risks, namely the risk of lower accuracy and reliability compared to traditional laboratory tests, quality control and connectivity issues, high dependence on operators (with varying levels of expertise or training), challenges related to patient data management, higher costs per individual test, regulatory and compliance issues such as the need for appropriate validation prior to clinical use (especially for rapid diagnostic tests; RDTs), as well as additional preanalytical sources of error that may remain undetected in this type of testing, which is usually based on whole blood samples (i.e., presence of interfering substances, clotting, hemolysis, etc.). There is no doubt that POCT is a breakthrough innovation in laboratory medicine, but the discussion on its appropriate use requires further debate and initiatives. This collective opinion paper, composed of abstracts of the lectures presented at the two-day expert meeting "Point-Of-Care-Testing: State of the Art and Perspective" (Venice, April 4-5, 2024), aims to provide a thoughtful overview of the state-of-the-art in POCT, its current applications, advantages and potential limitations, as well as some interesting reflections on the future perspectives of this particular field of laboratory medicine.

Recommendations for blood sampling in emergency departments from the European Society for Emergency Medicine (EUSEM), European Society for Emergency Nursing (EuSEN), and European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase. Executive summary.

AIM: Blood Sampling Guidelines have been developed to target European emergency medicine-related professionals involved in the blood sampling process (e.g. physicians, nurses, phlebotomists working in the ED), as well as laboratory physicians and other related professionals. The guidelines population focus on adult patients. The development of these blood sampling guidelines for the ED setting is based on the collaboration of three European scientific societies that have a role to play in the preanalytical phase process: EuSEN, EFLM, and EUSEM. The elaboration of the questions was done using the PICO procedure, literature search and appraisal was based on the GRADE methodology. The final recommendations were reviewed by an international multidisciplinary external review group. RESULTS: The document includes the elaborated recommendations for the selected sixteen questions. Three in pre-sampling, eight regarding sampling, three post-sampling, and two focus on quality assurance. In general, the quality of the evidence is very low, and the strength of the recommendation in all the questions has been rated as weak. The working group in four questions elaborate the recommendations, based mainly on group experience, rating as good practice. CONCLUSIONS: The multidisciplinary working group was considered one of the major contributors to this guideline. The lack of quality information highlights the need for research in this area of the patient care process. The peculiarities of the emergency medical areas need specific considerations to minimise the possibility of errors in the preanalytical phase.

EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) recommendations for reinforcing cyber-security and managing cyber-attacks in medical laboratories.

The healthcare systems are a prime target for cyber-attacks due to the sensitive nature of the information combined with the essential need for continuity of care. Medical laboratories are particularly vulnerable to cyber-attacks for a number of reasons, including the high level of information technology (IT), computerization and digitization. Based on reliable and widespread evidence that medical laboratories may be inadequately prepared for cyber-terrorism, a panel of experts of the Task Force Preparation of Labs for Emergencies (TF-PLE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has recognized the need to provide some general guidance that could help medical laboratories to be less vulnerable and better prepared for the dramatic circumstance of a disruptive cyber-attack, issuing a number of consensus recommendations, which are summarized and described in this opinion paper.

Red blood cell distribution width (RDW) reflects disease severity in patients with carbon monoxide poisoning: systematic literature review and meta-analysis.

No definitive prognostic biomarkers for carbon monoxide (CO) poisoning have been proposed. The aim of this study is to investigate, through a systematic literature review and pooled analysis, whether red blood cell distribution width (RDW) can predict disease severity in CO-poisoned patients. We performed an electronic search in Scopus and PubMed using the keywords: 'red blood cell distribution width' OR 'RDW' AND 'carbon monoxide' AND 'poisoning,' with no time or language restrictions (i.e. through August 2023) to find clinical studies that examined the value of RDW in patients with varying severity of CO poisoning. The analysis was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 reporting checklist. We identified 29 articles, seven of which were included in our analysis, with a total of 1979 CO-poisoned patients, 25.9% of whom were severely ill. In all but one of the studies, the RWD mean or median value was higher in CO-poisoned patients with severe disease. The weighted mean difference (WMD) of RDW was 0.36 (95% confidence interval (CI), 0.26-0.47)%. In the three articles in which the severity of illness in CO-poisoned patients was defined as cardiac injury, the WMD of the RDW was 1.26 (95%CI, 1.02-1.50)%. These results suggest that monitoring RDW in CO-poisoned patients may help to determine the severity of disease, particularly cardiac injury.

What We Know (and Do not Know) Regarding the Pathogenesis of Pulmonary Thrombosis in COVID-19.

The clinical course of coronavirus disease 2019 (COVID-19) is often complicated by the onset of venous thrombosis and thromboembolism (VTE), encompassing also pulmonary thrombosis. Recent statistics attests that the cumulative frequency of VTE can be as high as 30% in COVID-19 hospitalized patients, increasing to nearly 40 to 70% (depending on systematic screening) in those with severe illness, mechanical ventilation, or intensive care unit admission. The risk of venous thrombosis seems mostly limited to the active phase of disease, and is directly associated with some genetic (i.e., inherited prothrombotic predisposition) and demographical factors (male sex, overweight/obesity), disease severity (risk increasing progressively from hospitalization to development of severe illness, being the highest in patients needing mechanical ventilation and/or intensive care), presence and extent of pulmonary disease, coexistence of multiple risk factors (immobilization, mechanical ventilation, co- or superinfections), along with increased values of inflammatory and thrombotic biomarkers. At least three different phenotypes of pulmonary thrombosis may develop in COVID-19 patients, one caused by typical embolization from peripheral venous thrombosis (e.g., deep vein thrombosis), a second type triggered by local inflammation of nearby pulmonary tissue, and a third one mostly attributable to the prothrombotic state consequent to the pronounced systemic inflammatory response (i.e., the so-called cytokine storm) that is frequently observed in COVID-19. Although the pathogenesis of these three conditions has different features, their discrimination is essential for diagnostic and therapeutic purposes. The prognosis of COVID-19 patients who develop pulmonary thrombosis is also considerably worse than those who do not, thus probably needing frequent monitoring and more aggressive therapeutic management.