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1.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1939965

ABSTRACT

Cellular and humoral immune responses are essential for COVID-19 recovery and protection against SARS-CoV-2 reinfection. To date, the evaluation of SARS-CoV-2 immune protection has mainly focused on antibody detection, generally disregarding the cellular response, or placing it in a secondary position. This phenomenon may be explained by the complex nature of the assays needed to analyze cellular immunity compared with the technically simple and automated detection of antibodies. Nevertheless, a large body of evidence supports the relevance of the T cell’s role in protection against SARS-CoV-2, especially in vulnerable individuals with a weakened immune system (such as the population over 65 and patients with immunodeficiencies). Here we propose to use CoVITEST (Covid19 anti-Viral Immunity based on T cells for Evaluation in a Simple Test), a fast, affordable and accessible in-house assay that, together with a diagnostic matrix, allows us to determine those patients who might be protected with SARS-CoV-2-reactive T cells. The method was established using healthy SARS-CoV-2-naïve donors pre- and post-vaccination (n=30), and further validated with convalescent COVID-19 donors (n=51) in a side-by-side comparison with the gold standard IFN-γ ELISpot. We demonstrated that our CoVITEST presented reliable and comparable results to those obtained with the ELISpot technique in a considerably shorter time (less than 8 hours). In conclusion, we present a simple but reliable assay to determine cellular immunity against SARS-CoV-2 that can be used routinely during this pandemic to monitor the immune status in vulnerable patients and thereby adjust their therapeutic approaches. This method might indeed help to optimize and improve decision-making protocols for re-vaccination against SARS-CoV-2, at least for some population subsets.

2.
Crit Care ; 26(1): 199, 2022 07 04.
Article in English | MEDLINE | ID: covidwho-1916967

ABSTRACT

BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.


Subject(s)
COVID-19 , Pandemics , COVID-19/therapy , Critical Illness/epidemiology , Critical Illness/therapy , Female , Humans , Intensive Care Units , Middle Aged , Prospective Studies , Registries
3.
Int J Infect Dis ; 118: 197-202, 2022 May.
Article in English | MEDLINE | ID: covidwho-1838861

ABSTRACT

OBJECTIVES: We described the current incidence and risk factors of bacterial co-infection in hospitalized patients with COVID-19. METHODS: Observational cohort study was performed at the Hospital Clinic of Barcelona (February 2020-February 2021). All patients with COVID-19 who were admitted for >48 hours with microbiological sample collection and procalcitonin (PCT) determination within the first 48 hours were included. RESULTS: A total of 1125 consecutive adults met inclusion criteria. Co-infections were microbiologically documented in 102 (9.1%) patients. Most frequent microorganisms were Streptococcus pneumoniae (79%), Staphylococcus aureus (6.8%), and Haemophilus influenzae (6.8%). Test positivity was 1% (8/803) for blood cultures, 10.1% (79/780) for pneumococcal urinary antigen test, and 11.4% (15/132) for sputum culture. Patients with PCT higher than 0.2, 0.5, 1, and 2 ng/mL had significantly more co-infections than those with lower levels (p=0.017, p=0.031, p<0.001, and p<0.001, respectively). In multivariate analysis, oxygen saturation ≤94% (OR 2.47, CI 1.57-3.86), ferritin levels <338 ng/mL (OR 2.63, CI 1.69-4.07), and PCT higher than 0.2 ng/mL (OR 1.74, CI 1.11-2.72) were independent risk factors for co-infection at hospital admission owing to COVID-19. CONCLUSIONS: Bacterial co-infection in patients hospitalized for COVID-19 is relatively common. However, clinicians could spare antibiotics in patients with PCT values <0.2, especially with high ferritin values and oxygen saturation >94%.


Subject(s)
Bacterial Infections , COVID-19 , Coinfection , Adult , Bacterial Infections/microbiology , COVID-19/epidemiology , Coinfection/epidemiology , Ferritins , Hospitals , Humans , Procalcitonin , Retrospective Studies , SARS-CoV-2
4.
Infect Dis Ther ; 11(3): 1243-1251, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1813898

ABSTRACT

INTRODUCTION: Increased mortality has been reported in the Latin American population. The objective is to compare the clinical characteristics and outcome of Latin American and Spanish populations in a cohort of patients hospitalized with COVID-19 during the first year of the pandemic. METHODS: We retrospectively analysed all the Latin American patients (born in South or Central America) hospitalized in our centre from February 2020 to February 2021 and compared them with an age- and gender-matched group of Spanish subjects. Variables included were demographics, co-morbidities, clinical and analytical parameters at admission and treatment received. The primary outcomes were ICU admission and mortality at 60 days. A conditional regression analysis was performed to evaluate the independent baseline predictors of both outcomes. RESULTS: From the 3216 patients in the whole cohort, 216 pairs of case-controls (Latin American and Spanish patients, respectively) with same age and gender were analysed. COPD was more frequent in the Spanish group, while HIV was more prevalent in the Latin American group. Other co-morbidities showed no significant difference. Both groups presented with similar numbers of days from symptom onset, but the Latin American population had a higher respiratory rate (21 vs. 20 bpm, P = 0.041), CRP (9.13 vs. 6.22 mg/dl, P = 0.001), ferritin (571 vs. 383 ng/ml, P = 0.012) and procalcitonin (0.10 vs. 0.07 ng/ml, P = 0.020) at admission and lower cycle threshold of PCR (27 vs. 28.8, P = 0.045). While ICU admission and IVM were higher in the Latin American group (17.1% vs. 13% and 9.7% vs. 5.1%, respectively), this was not statistically significant. Latin American patients received remdesivir and anti-inflammatory therapies more often, and no difference in the 60-day mortality rate was found (3.2% for both groups). CONCLUSION: Latin American patients with COVID-19 have more severe disease than Spanish patients, requiring ICU admission, antiviral and anti-inflammatory therapies more frequently. However, the mortality rate was similar in both groups.

5.
Sci Rep ; 12(1): 5250, 2022 03 28.
Article in English | MEDLINE | ID: covidwho-1764201

ABSTRACT

Dexamethasone and tocilizumab have been associated with reduction in mortality, however, the beneficial effect is not for all patients and the impact on viral replication is not well defined. We hypostatized that C-reactive protein (CRP) could help in the identification of patients requiring anti-inflammatory therapy. Patients admitted for > 48 h in our hospital for a confirmed or suspected infection by SARS-CoV-2 from February 2020 to February 2021 were retrospectively evaluated. The primary outcome was mortality at 30 days. Demographics and the most relevant variables related with the outcome were included. CRP was stratified by percentiles. Univariate and multivariate analysis were performed. A total of 3218 patients were included with a median (IQR) age of 66 (74-78) years and 58.9% were males. The rate of intensive care unit admission was 24.4% and the 30-day mortality rate was 11.8%. Within the first 5 days from admission, 1018 (31.7%) patients received dexamethasone and 549 tocilizumab (17.1%). The crude analysis showed a mortality reduction in patients receiving dexamethasone when CRP was > 13.75 mg/dL and > 3.5 mg/dL for those receiving tocilizumab. Multivariate analysis identified the interaction of CRP > 13.75 mg/dL with dexamethasone (OR 0.57; CI 95% 0.37-0.89, P = 0014) and CRP > 3.5 mg/dL with tocilizumab (0.65; CI95%:0.44-0.95, P = 0.029) as independent predictors of mortality. Our results suggest that dexamethasone and tocilizumab are associated with a reduction in mortality when prescribed to patients with a certain inflammatory activity assessed by C-reactive protein.


Subject(s)
Antibodies, Monoclonal, Humanized , C-Reactive Protein , COVID-19 , Dexamethasone , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , C-Reactive Protein/metabolism , COVID-19/drug therapy , Dexamethasone/therapeutic use , Female , Humans , Male , Retrospective Studies , SARS-CoV-2
6.
Biomedicines ; 10(3)2022 Mar 19.
Article in English | MEDLINE | ID: covidwho-1760361

ABSTRACT

Immunologic and neuroinflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources, it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. For this reason, we performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways involved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugs.

7.
Am J Obstet Gynecol ; 227(2): 277.e1-277.e16, 2022 08.
Article in English | MEDLINE | ID: covidwho-1757079

ABSTRACT

BACKGROUND: COVID-19 presents a spectrum of signs and symptoms in pregnant women that might resemble preeclampsia. Differentiation between severe COVID-19 and preeclampsia is difficult in some cases. OBJECTIVE: To study biomarkers of endothelial damage, coagulation, innate immune response, and angiogenesis in preeclampsia and COVID-19 in pregnancy in addition to in vitro alterations in endothelial cells exposed to sera from pregnant women with preeclampsia and COVID-19. STUDY DESIGN: Plasma and sera samples were obtained from pregnant women with COVID-19 infection classified into mild (n=10) or severe (n=9) and from women with normotensive pregnancies as controls (n=10) and patients with preeclampsia (n=13). A panel of plasmatic biomarkers was assessed, including vascular cell adhesion molecule-1, soluble tumor necrosis factor-receptor I, heparan sulfate, von Willebrand factor antigen (activity and multimeric pattern), α2-antiplasmin, C5b9, neutrophil extracellular traps, placental growth factor, soluble fms-like tyrosine kinase-1, and angiopoietin 2. In addition, microvascular endothelial cells were exposed to patients' sera, and changes in the cell expression of intercellular adhesion molecule 1 on cell membranes and von Willebrand factor release to the extracellular matrix were evaluated through immunofluorescence. Changes in inflammation cell signaling pathways were also assessed by of p38 mitogen-activated protein kinase phosphorylation. Statistical analysis included univariate and multivariate methods. RESULTS: Biomarker profiles of patients with mild COVID-19 were similar to those of controls. Both preeclampsia and severe COVID-19 showed significant alterations in most circulating biomarkers with distinctive profiles. Whereas severe COVID-19 exhibited higher concentrations of vascular cell adhesion molecule-1, soluble tumor necrosis factor-α receptor I, heparan sulfate, von Willebrand factor antigen, and neutrophil extracellular traps, with a significant reduction of placental growth factor compared with controls, preeclampsia presented a marked increase in vascular cell adhesion molecule-1 and soluble tumor necrosis factor-α receptor I (significantly increased compared with controls and patients with severe COVID-19), with a striking reduction in von Willebrand factor antigen, von Willebrand factor activity, and α2-antiplasmin. As expected, reduced placental growth factor, increased soluble fms-like tyrosine kinase-1 and angiopoietin 2, and a very high soluble fms-like tyrosine kinase-1 to placental growth factor ratio were also observed in preeclampsia. In addition, a significant increase in C5b9 and neutrophil extracellular traps was also detected in preeclampsia compared with controls. Principal component analysis demonstrated a clear separation between patients with preeclampsia and the other groups (first and second components explained 42.2% and 13.5% of the variance), mainly differentiated by variables related to von Willebrand factor, soluble tumor necrosis factor-receptor I, heparan sulfate, and soluble fms-like tyrosine kinase-1. Von Willebrand factor multimeric analysis revealed the absence of von Willebrand factor high-molecular-weight multimers in preeclampsia (similar profile to von Willebrand disease type 2A), whereas in healthy pregnancies and COVID-19 patients, von Willebrand factor multimeric pattern was normal. Sera from both preeclampsia and severe COVID-19 patients induced an overexpression of intercellular adhesion molecule 1 and von Willebrand factor in endothelial cells in culture compared with controls. However, the effect of preeclampsia was less pronounced than the that of severe COVID-19. Immunoblots of lysates from endothelial cells exposed to mild and severe COVID-19 and preeclampsia sera showed an increase in p38 mitogen-activated protein kinase phosphorylation. Patients with severe COVID-19 and preeclampsia were statistically different from controls, suggesting that both severe COVID-19 and preeclampsia sera can activate inflammatory signaling pathways. CONCLUSION: Although similar in in vitro endothelial dysfunction, preeclampsia and severe COVID-19 exhibit distinctive profiles of circulating biomarkers related to endothelial damage, coagulopathy, and angiogenic imbalance that could aid in the differential diagnosis of these entities.


Subject(s)
Biomarkers , COVID-19 , Pre-Eclampsia , Angiopoietin-2 , Biomarkers/blood , COVID-19/diagnosis , Endothelial Cells , Female , Heparitin Sulfate , Humans , Intercellular Adhesion Molecule-1 , Placenta Growth Factor , Pre-Eclampsia/diagnosis , Pregnancy , Tumor Necrosis Factor-alpha , Vascular Cell Adhesion Molecule-1 , Vascular Endothelial Growth Factor Receptor-1 , p38 Mitogen-Activated Protein Kinases , von Willebrand Factor
8.
Sci Rep ; 12(1): 3563, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1730317

ABSTRACT

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.


Subject(s)
COVID-19/psychology , Cognition Disorders/psychology , Mental Disorders/psychology , COVID-19/virology , Humans , SARS-CoV-2/isolation & purification , Severity of Illness Index
9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321084

ABSTRACT

Background: Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains, it impacts on quality of life and the possible existence of related biomarkers. Methods: : Cross-sectional study of patients who survived severe infection with SARS-CoV-2 consecutively recruited from 13 neurology services in Spain between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory factors (chemokines), and neurotrophic factors and light-chain neurofilaments. A Principal Component Analysis extracted the main independent characteristics of the syndrome. Results: : 152 patients were recruited. The results of our study show a pattern of cognitive impairment with preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of information processing speed, denomination, verbal fluency, and other cortical functions. In addition, psychiatric affectation such as anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population, suggesting a pro-inflammatory chronic state derived of viral infection. Conclusion: The neurologic Subacute Impairment in severe Covid-19 consist in an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and, in this case, if this can trigger or accelerate the onset of neurodegenerative diseases.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317308

ABSTRACT

Background: Critically ill patients with coronavirus disease 19 (COVID-19) have a high fatality rate likely due to a dysregulated immune response. Corticosteroids could attenuate this inappropriate response, although there are still some concerns regarding its use, timing, and dose. Methods: : This is a nationwide, prospective, multicenter, observational, cohort study in critically ill adult patients with COVID-19 admitted into Intensive Care Units (ICU) in Spain from March 12 th to June 29 th , 2020. Using a multivariable Cox model with inverse probability weighting, we compared relevant outcomes between patients treated with early corticosteroids (before or within the first 48h of ICU admission) with those who did not receive early corticosteroids or any corticosteroids at all. Primary endpoint was ICU mortality. Secondary endpoints included 7-day mortality, ventilator-free days, and complications. Results: : A total of 691 patients out of 882 (78.3%) received corticosteroid during their hospital stay. Patients treated with early-corticosteroids (n=485) had a lower ICU mortality (30.3% vs 40.6%, HR 0.71, 95% CI 0.57-0.89) and higher number of ventilator-free days (mean difference 2.5 days, 95% CI 1.3-3.8) compared to non-early treated patients. There were no differences in 7-day mortality (HR 0.76, 95% CI 0.48-1.2), medical complications (OR 2.18, 95% CI 0.91-5.25) or secondary infections (OR 0.88, 95% CI 0.67-1.15) between both groups. Of note, early use of moderate-to-high doses was associated with better outcomes than low dose regimens. Conclusion: Early use of corticosteroids in critically ill patients with COVID-19 is associated with lower mortality (10.3% absolute risk reduction) and shorter duration of mechanical ventilation.

12.
Clin Infect Dis ; 74(1): 127-132, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1621567

ABSTRACT

Hospitalized patients with coronavirus disease 2019 (COVID-19) experiencing respiratory symptoms have different complications (inflammatory, co-infection, and thrombotic) that are identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (odds ratio [OR] .144; 95% confidence interval [CI] .03-.686; P = .015). Increasing age (OR 1.06; P = .038) and therapeutic effort limitation (OR 9.684; P < .001) were associated with higher mortality.


Subject(s)
COVID-19 , Hospitalization , Humans , Odds Ratio , SARS-CoV-2
13.
Clin Infect Dis ; 73(Suppl_5): S454-S464, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1577471

ABSTRACT

BACKGROUND: Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure. METHODS: From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs. CONCLUSIONS: MITS is useful for evaluating COVID-19-related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA.


Subject(s)
COVID-19 , Autopsy , Humans , Personal Protective Equipment , Real-Time Polymerase Chain Reaction , SARS-CoV-2
14.
Clin Infect Dis ; 73(Suppl_5): S472-S479, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1573816

ABSTRACT

BACKGROUND: Infectious diseases' outbreak investigation requires, by definition, conducting a thorough epidemiological assessment while simultaneously obtaining biological samples for an adequate screening of potential responsible pathogens. Complete autopsies remain the gold-standard approach for cause-of-death evaluation and characterization of emerging diseases. However, for highly transmissible infections with a significant associated lethality, such as COVID-19, complete autopsies are seldom performed due to biosafety challenges, especially in low-resource settings. Minimally invasive tissue sampling (MITS) is a validated new approach based on obtaining postmortem samples from key organs and body fluids, a procedure that does not require advanced biosafety measures or a special autopsy room. METHODS: We aimed to review the use of MITS or similar procedures for outbreak investigation up to 27 March 2021 and their performance for evaluating COVID-19 deaths. RESULTS: After a literature review, we analyzed in detail the results of 20 studies conducted at international sites, whereby 216 COVID-19-related deaths were investigated. MITS provided a general and more granular understanding of the pathophysiological changes secondary to the infection and high-quality samples where the extent and degree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related damage could be evaluated. CONCLUSIONS: MITS is a useful addition in the investigation and surveillance of infections occurring in outbreaks or epidemics. Its less invasive nature makes the tool more acceptable and feasible and reduces the risk of procedure-associated contagion, using basic biosafety measures. Standardized approaches protocolizing which samples should be collected-and under which exact biosafety measures-are necessary to facilitate and expand its use globally.


Subject(s)
COVID-19 , Autopsy , Humans , Pandemics , SARS-CoV-2
15.
Shock ; 57(1): 95-105, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1574295

ABSTRACT

BACKGROUND: Endotheliopathy is a key element in COVID-19 pathophysiology, contributing to both morbidity and mortality. Biomarkers distinguishing different COVID-19 phenotypes from sepsis syndrome remain poorly understood. OBJECTIVE: To characterize circulating biomarkers of endothelial damage in different COVID-19 clinical disease stages compared with sepsis syndrome and normal volunteers. METHODS: Patients with COVID-19 pneumonia (n = 49) were classified into moderate, severe, or critical (life-threatening) disease. Plasma samples were collected within 48 to 72 h of hospitalization to analyze endothelial activation markers, including soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), von Willebrand Factor (VWF), A disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 (ADAMTS-13) activity, thrombomodulin (TM), and soluble TNF receptor I (sTNFRI); heparan sulfate (HS) for endothelial glycocalyx degradation; C5b9 deposits on endothelial cells in culture and soluble C5b9 for complement activation; circulating dsDNA for neutrophil extracellular traps (NETs) presence, and α2-antiplasmin and PAI-1 as parameters of fibrinolysis. We compared the level of each biomarker in all three COVID-19 groups and healthy donors as controls (n = 45). Results in critically ill COVID-19 patients were compared with other intensive care unit (ICU) patients with septic shock (SS, n = 14), sepsis (S, n = 7), and noninfectious systemic inflammatory response syndrome (NI-SIRS, n = 7). RESULTS: All analyzed biomarkers were increased in COVID-19 patients versus controls (P < 0.001), except for ADAMTS-13 activity that was normal in both groups. The increased expression of sVCAM-1, VWF, sTNFRI, and HS was related to COVID-19 disease severity (P < 0.05). Several differences in these parameters were found between ICU groups: SS patients showed significantly higher levels of VWF, TM, sTNFRI, and NETS compared with critical COVID-19 patients and ADAMTS-13 activity was significantly lover in SS, S, and NI-SIRS versus critical COVID-19 (P < 0.001). Furthermore, α2-antiplasmin activity was higher in critical COVID-19 versus NI-SIRS (P < 0.01) and SS (P < 0.001), whereas PAI-1 levels were significantly lower in COVID-19 patients compared with NI-SIRS, S, and SS patients (P < 0.01). CONCLUSIONS: COVID-19 patients present with increased circulating endothelial stress products, complement activation, and fibrinolytic dysregulation, associated with disease severity. COVID-19 endotheliopathy differs from SS, in which endothelial damage is also a critical feature of pathobiology. These biomarkers could help to stratify the severity of COVID-19 disease and may also provide information to guide specific therapeutic strategies to mitigate endotheliopathy progression.


Subject(s)
COVID-19/blood , ADAMTS13 Protein/blood , Aged , Biomarkers/blood , Complement Membrane Attack Complex/analysis , DNA/blood , Female , Heparitin Sulfate/blood , Humans , Male , Middle Aged , Patient Acuity , Plasminogen Activator Inhibitor 1/blood , Prospective Studies , Receptors, Tumor Necrosis Factor, Type I/blood , Sepsis/blood , Thrombomodulin/blood , Vascular Cell Adhesion Molecule-1/blood , alpha-2-Antiplasmin/analysis , von Willebrand Factor/analysis
16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295970

ABSTRACT

Background: Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Methods: : Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A Principal Component Analysis extracted the main independent characteristics of the syndrome. Results: : 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Conclusion: Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.

17.
Int J Environ Res Public Health ; 18(21)2021 10 21.
Article in English | MEDLINE | ID: covidwho-1512277

ABSTRACT

Intensive care unit discharge is an important transition that impacts a patient's wellbeing. Nurses can play an essential role in this scenario, potentiating patient empowerment. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (the PRISMA Statement. Embase), PubMed/MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), CUIDEN Plus, and LILACS databases; these were evaluated in May 2021. Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of evidence. Quality of the studies included was assessed using the Cochrane risk-of-bias tool. Of the 274 articles initially identified, eight randomized controlled trials that reported on nursing interventions had mainly focused on patients' ICU discharge preparation through information and education. The creation of ICU nurse-led teams and nurses' involvement in critical care multidisciplinary teams also aimed to support patients during ICU discharge. This systematic review provides an update on the clinical practice aimed at improving the patient experience during ICU discharge. The main nursing interventions were based on information and education, as well as the development of new nursing roles. Understanding transitional needs and patient empowerment are key to making the transition easier.


Subject(s)
Intensive Care Units , Patient Participation , Critical Care , Humans , Patient Discharge
18.
Head Neck ; 43(12): 3743-3756, 2021 12.
Article in English | MEDLINE | ID: covidwho-1409182

ABSTRACT

BACKGROUND: Optimal timing for tracheotomy for critically ill COVID-19 patients requiring invasive mechanical ventilation (IMV) is not established. METHODS: Multicenter prospective cohort including all COVID-19 patients admitted to intensive care units (ICUs) in 36 hospitals who required tracheotomy during first pandemic wave. With a target emulation trial framework, we studied the causal effects of early (7-10 days) versus late (>10 days) tracheotomy (LT) on time from tracheotomy to weaning, postoperative mortality, and tracheotomy complications. RESULTS: Of 696 patients, 20.4% received early tracheotomy (ET). ET was associated with faster weaning (hazard ratio [HR] [95% confidence interval, CI]: 1.25 [1.00-1.56]) without differences in mortality (HR [95% CI]: 0.85 [0.60-1.21]) or complications (adjusted rate ratio [95% CI]: 0.56 [0.23-1.33]). CONCLUSIONS: ET had a similar or lower post-tracheotomy weaning time than LT, potentially shortening IMV and ICU stays, without changing complication or mortality rates in COVID-19 patients.


Subject(s)
COVID-19 , Respiration, Artificial , Critical Care , Humans , Intensive Care Units , Prospective Studies , SARS-CoV-2 , Tracheotomy
19.
J Antimicrob Chemother ; 76(12): 3296-3302, 2021 11 12.
Article in English | MEDLINE | ID: covidwho-1393280

ABSTRACT

BACKGROUND: The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality. METHODS: Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality. RESULTS: In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54-77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4-6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218-0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration (<6 days). CONCLUSIONS: Patients with ≤3 days and 4-6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.


Subject(s)
COVID-19 , Adenosine Monophosphate/analogs & derivatives , Aged , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Male , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
20.
Blood ; 136(Supplement 1):31-32, 2020.
Article in English | PMC | ID: covidwho-1339067

ABSTRACT

Background: Clinical and analytical data on patients suffering from coronavirus disease-2019 (COVID-19) indicate that endothelial damage plays a key role in the pathophysiology of the disease and is responsible for the pulmonary complications and the thrombotic microangiopathy affecting multiple organs, which contribute directly to mortality (Ackerman et al. N Engl J Med 2020). Detection of biomarkers of endothelial injury in circulating blood may provide critical diagnostic and prognostic information on the disease course (Goshua et al. Lancet Haematology 2020). Endothelial injury is also a cornerstone of pathobiology in other septic and potentially life-threatening inflammatory syndromes.Objectives: To identify circulating markers of endothelial damage in COVID-19 patients, and compare their levels with those observed in other septic syndromes.Methods: Plasma samples from non-critically ill patients with confirmed COVID-19 pneumonia (positive nasopharyngeal swab and confirmatory radiological chest imaging) requiring admission (n=42) were collected during the first 36h of hospitalization. Endothelial damage was evaluated by measuring in plasma: i) markers of endothelial function and activation (sVCAM-1, VWF, ADAMTS-13 activity, Protein C and α2-antiplasmin as a marker of fibrinolysis);ii) heparan sulfate (HS) levels, as indicators of endothelial glycocalyx degradation and loss of endothelial barrier function;and iii) C5b9 deposits on endothelial cells in culture, and soluble C5b9 (sC5b9) levels, to measure complement activation. Circulating dsDNA was analyzed as an indicator of the presence of neutrophil extracellular traps (NETs). ELISA tests were used for sVCAM-1, Protein C, HS, and sC5b9 levels. ADAMTS-13 activity was evaluated by FRETS. VWF, Protein C, and α2-antiplasmin were measured at the Atellica COAG 360 (Siemens Healthineers). C5b9 deposits were assessed by immunofluorescence and dsDNA levels by Quant-iT PicoGreen assay kit. Results were compared with those obtained in healthy donors (controls, n=45), and patients with non-infectious systemic inflammatory response syndrome (NI-SIRS, n=8) and septic shock (SS, n=8).Results: Levels of sVCAM-1 were significantly higher in COVID-19 patients vs. controls, NI-SIRS and SS (159±12 vs. 79±4, 57±8 and 80±10 ng/mL, respectively, p<0.005) (Mean±SDM). VWF was elevated in COVID-19 patients vs. controls (240±26 vs. 96±5%, p<0.001), with similar values in NI-SIRS (271±40%), and significantly reduced vs. SS (476±43%, p<0.001). HS levels in COVID-19 patients were twice those detected in controls (1669±174 vs. 839±36 ng/mL, p=0.001), but they did not differ from those in NI-SIRS (1372±368 ng/mL), and were significantly lower than in SS (3677±880 ng/mL, p<0.001 vs COVID-19). Regarding complement activation, deposits of C5b9 on endothelial cells were significantly increased vs. controls (2-fold, p<0.01), with no notable differences vs. NI-SIRS (3±1-fold) and significantly lower than in SS (8±2-fold, p<0.001). Remarkably, sC5b9 levels were much more elevated in COVID-19 patients (1064±120 vs. 204±11 ng/mL, p<0.001), and no significant differences were observed vs. NI-SIRS (902±160 ng/mL) or SS (958±180 ng/mL). Also of note, presence of NETs was significantly elevated in the plasma of COVID-19 patients vs. controls (16±1.3 vs. 2±0.3 ng/ml, p<0.001), but similar to NI-SIRS (19±5 ng/mL) and clearly inferior to SS (33±6 ng/mL, p<0.001) (Figure). Importantly and in contrast, ADAMTS-13 activity, Protein C, and α2-antiplasmin values were within the normal range in COVID-19 patients.Conclusions: Our data clearly demonstrate the presence of endothelial stress products in the circulating blood of non-critically ill COVID-19 patients. These biomarkers of endothelial injury are suggestive indicators of different aspects of the disease: specifically, release of acute phase reactants, degradation of the endothelial cell glycocalyx, and activation of the complement system. Furthermore, this profile of biomarkers in COVID-19 appears spec fic, with a differential behavior in comparison with septic shock, in which endothelial damage is also known to be critical. Additional studies are needed to validate these biomarkers as diagnostic and prognostic tools of the endothelial complications in COVID-19 patients, both in early disease and later, as well as supporting specific forms of therapeutic intervention.Figure

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