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Therapeutic vaccines based on monocyte-derived dendritic cells have been shown to be promising strategies and may act as complementary treatments for viral infections, cancers, and, more recently, autoimmune diseases. Alpha-type-1-polarized dendritic cells (aDC1s) have been shown to induce type-1 immunity with a high capacity to produce interleukin-12p70 (IL-12p70). In the clinical use of cell-based therapeutics, injectable solutions can affect the morphology, immunophenotypic profile, and viability of cells before delivery and their survival after injection. In this sense, preparing a cell suspension that maintains the quality of aDC1s is essential to ensure effective immunotherapy. In the present study, monocytes were differentiated into aDC1s in the presence of IL-4 and GM-CSF. On day 5, the cells were matured by the addition of a cytokine cocktail consisting of IFN-α, IFN-γ, IL-1ß, TNF-α, and Poly I:C. After 48 hr, mature aDC1s were harvested and suspended in two different solutions: normal saline and Ringer's lactate. The maintenance of cells in suspension was evaluated after 4, 6, and 8 hr of storage. Cell viability, immunophenotyping, and apoptosis analyses were performed by flow cytometry. Cellular morphology was observed by electron microscopy, and the production of IL-12p70 by aDC1s was evaluated by ELISA. Compared with normal saline, Ringer's lactate solution was more effective at maintaining DC viability for up to 8 hr of incubation at 4 or 22°C.

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Atopic dermatitis, commonly referred to as atopic eczema, is a persistent inflammatory skin disorder that predominantly manifests in children but may endure into adulthood. Its clinical management poses challenges due to the absence of a definitive cure, and its prevalence varies across ethnicities, genders, and geographic locations. The epigenetic landscape of AD includes changes in DNA methylation, changes in histone acetylation and methylation, and regulation by non-coding RNAs. These changes affect inflammatory and immune mechanisms, and research has identified AD-specific variations in DNA methylation, particularly in the affected epidermis. Histone modifications, including acetylation, have been associated with the disruption of skin barrier function in AD, suggesting the potential therapeutic benefit of histone deacetylase inhibitors such as belinostat. Furthermore, non-coding RNAs, particularly microRNAs and long non-coding RNAs (lncRNAs), have been implicated in modulating various cellular processes central to AD pathogenesis. Therapeutic implications in AD include the potential use of DNA methylation inhibitors and histone deacetylase inhibitors to correct aberrant methylation patterns and modulate gene expression related to immune responses and skin barrier functions. Additionally, the emerging role of lncRNAs suggests the possibility of using small interfering RNAs or antisense oligonucleotides to inhibit lncRNAs and adjust their regulatory impact on gene expression. In conclusion, the importance of epigenetic elements in AD is becoming increasingly clear as studies highlight the contribution of DNA methylation, histone modifications and, control by non-coding RNAs to the onset and progression of the disease. Understanding these epigenetic changes provides valuable insights for developing targeted therapeutic strategies.

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Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency. Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output. Results: Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19. Discussion: Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.

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Zika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_ΔSTP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_ΔSTP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-ΔSTP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_ΔSTP+Alum protected adult mice upon viral challenge. Collectively, the ZK_ΔSTP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.

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Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

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[This corrects the article DOI: 10.3389/fimmu.2024.1307546.].

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Introduction: The COVID-19 pandemic may lead to reduced physical activity (PA) in health care workers (HCWs). Objective: To evaluate leisure and transport-related PA in HCW of a COVID-19-dedicated hospital during the first wave of the COVID-19 pandemic. Methods: This is a cross-sectional study with a sample of 1,527 HCWs. Socioeconomic aspects, occupational characteristics, and engagement in leisure and transport-related PA were investigated through an online survey administered in August of 2020. Results: More than 80 % HCWs performed < 150 min/week of leisure-related PA, and 85 % performed ≤ 30 min/day transport-related PA. Being male was associated with more PA (OR: 1.93; 95 % CI:1.40-2.66) and transport-related PA; working in nursing, physical therapy, and cleaning/housekeeping services was associated with low PA (OR: 0.70; 95 % CI:0.51-0.95). Physicians and administrative staff were less active in transport-related PA. Conclusions: HCWs working in a COVID-19 hospital had low levels of PA in the domains of leisure and transportation.

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In this study, high-throughput sequencing of 16S rRNA amplicons and predictive PICRUSt functional profiles were used to perform a comprehensive analysis of the temporal bacterial distribution and metabolic functions of 19 bimonthly samples collected from July 2019 to January 2020 in the surface water of Billings Reservoir, São Paulo. The results revealed that most of the bacterial 16S rRNA gene sequences belonged to Cyanobacteria and Proteobacteria, which accounted for more than 58% of the total bacterial abundance. Species richness and evenness indices were highest in surface water from summer samples (January 2020), followed by winter (July 2019) and spring samples (September and November 2019). Results also showed that the highest concentrations of sulfate (SO4-2), phosphate (P), ammonia (NH3), and nitrate (NO3-) were detected in November 2019 and January 2020 compared with samples collected in July and September 2019 (P < 0.05). Principal component analysis suggests that physicochemical factors such as pH, DO, temperature, and NH3 are the most important environmental factors influencing spatial and temporal variations in the community structure of bacterioplankton. At the genus level, 18.3% and 9.9% of OTUs in the July and September 2019 samples, respectively, were assigned to Planktothrix, while 14.4% and 20% of OTUs in the November 2019 and January 2020 samples, respectively, were assigned to Microcystis. In addition, PICRUSt metabolic analysis revealed increasing enrichment of genes in surface water associated with multiple metabolic processes rather than a single regulatory mechanism. This is the first study to examine the temporal dynamics of bacterioplankton and its function in Billings Reservoir during the winter, spring, and summer seasons. The study provides comprehensive reference information on the effects of an artificial habitat on the bacterioplankton community that can be used to interpret the results of studies to evaluate and set appropriate treatment targets.

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ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

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Several disturbances in T-cell mediated immunity have been described during aging, but immunosenescence of the B-cell compartment is less well elucidated. The peripheral blood B-cell compartment (CD19+) can be split into six main subpopulations according to the cell surface markers IgD, CD27, CD24, and CD38: Transitional, naïve, unswitched, switched, double negative and plasmablasts. We thus aimed to verify whether shifts in these subsets occur during healthy and pathological aging. We recruited three groups of aged people (> 60 years old), healthy, COPD patients, and smokers without altered pulmonary function test, and a fourth group of individuals 18-40 years old (youngs). Total B-cells percentage and absolute number were similar among the healthy aged, COPD patients, and youngs, but the smokers showed significantly higher absolute numbers. While all six B-cell subset percentages were comparable among the healthy aged, COPD patients, and youngs, smokers showed significantly higher percentages of switched B-cells and reduced naïve B-cells than the other three groups, resulting in an inverted naive:switched ratio. Analysis of the cell subset absolute numbers showed a similar trend. Overall, our results suggest that aging drives milder alterations in the distribution of peripheral blood B-cell subpopulations than in the T-cell compartment. We suggest that it is the T-cell immunosenescence that most contributes to the poor humoral immune responses in the elderly, vaccine responses included. Surprisingly it was the smokers who showed significant alterations when compared with the youngs, healthy aged, and aged COPD patients, probably as a result of the chronic immune stimulation described in active smoking subjects.

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In this study, high-throughput sequencing of 16S rRNA amplicons and predictive PICRUSt functional profiles were used to perform a comprehensive analysis of the temporal bacterial distribution and metabolic functions of 19 bimonthly samples collected from July 2019 to January 2020 in the surface water of Billings Reservoir, São Paulo. The results revealed that most of the bacterial 16S rRNA gene sequences belonged to Cyanobacteria and Proteobacteria, which accounted for more than 58% of the total bacterial abundance. Species richness and evenness indices were highest in surface water from summer samples (January 2020), followed by winter (July 2019) and spring samples (September and November 2019). Results also showed that the highest concentrations of sulfate (SO4–2), phosphate (P), ammonia (NH3), and nitrate (NO3-) were detected in November 2019 and January 2020 compared with samples collected in July and September 2019 (P < 0.05). Principal component analysis suggests that physicochemical factors such as pH, DO, temperature, and NH3 are the most important environmental factors influencing spatial and temporal variations in the community structure of bacterioplankton. At the genus level, 18.3% and 9.9% of OTUs in the July and September 2019 samples, respectively, were assigned to Planktothrix, while 14.4% and 20% of OTUs in the November 2019 and January 2020 samples, respectively, were assigned to Microcystis. In addition, PICRUSt metabolic analysis revealed increasing enrichment of genes in surface water associated with multiple metabolic processes rather than a single regulatory mechanism. This is the first study to examine the temporal dynamics of bacterioplankton and its function in Billings Reservoir during the winter, spring, and summer seasons. The study provides comprehensive reference information on the effects of an artificial habitat on the bacterioplankton community that can be used to interpret the results of studies to evaluate and set appropriate treatment targets.

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Restricted movement among populations decreases genetic variation, which may be the case for the Montezuma quail (Cyrtonyx montezumae), a small game bird that rarely flies long distances. In the northern limit of its distribution, it inhabits oak-juniper-pine savannas of Arizona, New Mexico, and Texas. Understanding genetic structure can provide information about the demographic history of populations that is also important for conservation and management. The objective of this study was to determine patterns of genetic variation in Montezuma quail populations using nine DNA microsatellite loci. We genotyped 119 individuals from four study populations: Arizona, Western New Mexico, Central New Mexico, and West Texas. Compared to other quail, heterozygosity was low (H¯0 = 0.22 ± 0.04) and there were fewer alleles per locus (A = 2.41 ± 0.27). The global population genetic differentiation index RST = 0.045 suggests little genetic structure, even though a Bayesian allocation analysis suggested three genetic clusters (K = 3). This analysis also suggested admixture between clusters. Nevertheless, an isolation-by-distance analysis indicates a strong correlation (r = 0.937) and moderate evidence (P = 0.032) of non-independence between geographical and genetic distances. Climate change projections indicate an increase in aridity for this region, especially in temperate ecosystems where the species occurs. In this scenario, corridors between the populations may disappear, thus causing their complete isolation.

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INTRODUCTION: Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature. OBJECTIVE: To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE. METHODS: 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated. RESULTS: JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 (p = 0.713), as well as between patients with and without current use of prednisone (p = 0.420), azathioprine (p = 1.0), mycophenolate mofetil (p = 0.185), and methotrexate (p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups (p > 0.05). CONCLUSION: This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. ( www. CLINICALTRIALS: gov , NCT03540823).

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Intracellular peptides (InPeps) generated by the orchestrated action of the proteasome and intracellular peptidases have biological and pharmacological significance. Here, human plasma relative concentration of specific InPeps was compared between 175 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and 45 SARS-CoV-2 non-infected patients; 2,466 unique peptides were identified, of which 67% were InPeps. The results revealed differences of a specific group of peptides in human plasma comparing non-infected individuals to patients infected by SARS-CoV-2, following the results of the semi-quantitative analyses by isotope-labeled electrospray mass spectrometry. The protein-protein interactions networks enriched pathways, drawn by genes encoding the proteins from which the peptides originated, revealed the presence of the coronavirus disease/COVID-19 network solely in the group of patients fatally infected by SARS-CoV-2. Thus, modulation of the relative plasma levels of specific InPeps could be employed as a predictive tool for disease outcome.

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Small RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell lymphotropic virus type 1 (HTLV-1), an oncogenic human retrovirus originally discovered in a patient with adult T-cell leukemia/lymphoma. Here, we describe the sRNA profile of a 30-year-old woman with ATLL at the time of diagnosis and after maintenance therapy with the aim of correlating expression levels with response to therapy.

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Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1-infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.

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INTRODUCTION: Influenza A (H3N2) virus is the major cause of morbidity/mortality due to seasonal influenza over 50 years. Data about the safety/immunogenicity of influenza A/Singapore (H3N2) vaccine are scarce in primary Sjögren syndrome (pSS). METHODS: Twenty-one consecutive pSS patients and 42 HC (healthy control individuals) were immunized with influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus. Rates of SP (seroprotection) and SC (seroconversion), GMT (geometric mean titers), FI-GMT (factor increase in GMT), ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), and adverse events were appraised before and 4 weeks post-vaccination. RESULTS: pSS and HC had similar mean age (51.2 ± 14.2 vs. 50.6 ± 12.1 years, p = 0.886). Pre-vaccination SP rates were high in pSS and HC (90.5% vs. 71.4%, p = 0.114), and GMT were higher in pSS [80.0 (52.4-160.0) vs. 40.0 (20.0-80.0), p = 0.001]. The percentage of influenza vaccination in the preceding two years was elevated and similar in pSS and HC (94.1% vs. 94.6%, p = 1.000). GMT values augmented in both groups four weeks after vaccination and persisted higher in the first group [160.0 (80.0-320.0) vs. 80.0 (40.0-80.0), p < 0.001] with equivalent FI-GMT [1.4 (1.0-2.8) vs. 1.4 (1.0-2.0), p = 0.410]. Both groups had low and similar SC rates (19.0% vs. 9.5%, p = 0.423). ESSDAI values persisted steadily during the study (p = 0.313). No serious adverse events have occurred. CONCLUSION: The novel demonstration that the influenza A/Singapore (H3N2) vaccine induces a different pattern of immunogenicity from other influenza A constituents in pSS, featured by a desirable high pre- and post-vaccination immunogenicity, is in line with reported differences in immune responses between strains in trivalent vaccines and may be related to pre-existing immunity. CLINICALTRIALS: gov: #NCT03540823. Key Points • This prospective study demonstrated a robust pre- and post-vaccination immunogenicity to influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus in primary Sjögren's syndrome (pSS). • This high immunogenicity pattern may be related to pre-existing immunization, or else it is related to immunogenicity differences of each strain. • This vaccine had an adequate safety profile in pSS, with no impact on disease activity.

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OBJECTIVE: COVID-19 is associated with an elevated risk of thromboembolism and excess mortality. Difficulties with best anticoagulation practices and their implementation motivated the current analysis of COVID-19 patients who developed Venous Thromboembolism (VTE). METHOD: This is a post-hoc analysis of a COVID-19 cohort, described in an economic study already published. The authors analyzed a subset of patients with confirmed VTE. We described the characteristics of the cohort, such as demographics, clinical status, and laboratory results. We tested differences amid two subgroups of patients, those with VTE or not, with the competitive risk Fine and Gray model. RESULTS: Out of 3186 adult patients with COVID-19, 245 (7.7%) were diagnosed with VTE, 174 (5.4%) of them during admission to the hospital. Four (2.3% of these 174) did not receive prophylactic anticoagulation and 19 (11%) discontinued anticoagulation for at least 3 days, resulting in 170 analyzed. During the first week of hospitalization, the laboratory most altered results were C-reactive protein and D-dimer. Patients with VTE were more critical, had a higher mortality rate, worse SOFA score, and, on average, 50% longer hospital stay. CONCLUSION: Proven VTE incidence in this severe COVID-19 cohort was 7.7%, despite 87% of them complying completely with VTE prophylaxis. The clinician must be aware of the diagnosis of VTE in COVID-19, even in patients receiving proper prophylaxis.

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