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1.
Front Immunol ; 15: 1443096, 2024.
Article in English | MEDLINE | ID: mdl-39176097

ABSTRACT

Introduction: Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression. Methods: We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission. Results: Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71). Discussion: Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.


Subject(s)
Biomarkers , Influenza, Human , Interleukin-15 , Interleukin-8 , Humans , Influenza, Human/immunology , Influenza, Human/blood , Male , Female , Biomarkers/blood , Prognosis , Middle Aged , Interleukin-15/blood , Aged , Prospective Studies , Interleukin-8/blood , Adult
3.
Front Public Health ; 11: 1171975, 2023.
Article in English | MEDLINE | ID: mdl-37841720

ABSTRACT

The randomized clinical trial (RCT) is the ideal and mandatory type of study to verify the effect and safety of a drug. Our aim is to examine the fundamental characteristics of interventional clinical trials on influenza and respiratory syncytial virus (RSV). This is a cross-sectional study of RCTs on influenza and RSV in humans between 2014 and 2021 registered in ClinicalTrials.gov. A total of 516 studies were identified: 94 for RSV, 423 for influenza, and 1 for both viruses. There were 51 RCTs of RSV vaccines (54.3%) and 344 (81.3%) for influenza virus vaccines (p < 0.001). Twelve (12.8%) RCTs for RSV were conducted only with women, and 6 were conducted only with pregnant women; for RCTs for influenza, 4 (0.9%) and 3, respectively. For RSV, 29 (31%) of the RCTs were exclusive to people under 5 years of age, and 21 (5%) for influenza virus (p < 0.001). For RSV, there are no RCTs exclusively for people older than or equal to 65 years and no phase 4 trials. RCTs on influenza virus and RSV has focused on vaccines. For the influenza virus, research has been consolidated, and for RSV, research is still in the development phase and directed at children and pregnant women.


Subject(s)
Influenza Vaccines , Influenza, Human , Orthomyxoviridae , Respiratory Syncytial Virus Infections , Child, Preschool , Female , Humans , Infant , Pregnancy , Cross-Sectional Studies , Influenza, Human/prevention & control , Randomized Controlled Trials as Topic , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Viruses
4.
Int J Infect Dis ; 136: 37-42, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37669725

ABSTRACT

BACKGROUND: Little is known about the incidence of influenza among admissions to the cardiac intensive care unit (C-ICU), accuracy of clinical suspicion, and influenza vaccination uptake. We evaluated the incidence of influenza at C-ICU admission during the influenza season, potential underdiagnosis, and vaccination uptake. METHODS: Prospective study at five C-ICUs during the 2017-2020 influenza seasons. A nasopharyngeal swab was collected at admission from patients who consented (n = 788). Testing was with Xpert®XpressFlu/RSV. RESULTS: Influenza was detected in 43 patients (5.5%) (40 FluA; 3 FluB) and clinically suspected in 27 (62.8%). Compared to patients without influenza, patients with influenza more frequently had heart failure (37.2% vs 22.8%, P = 0.031), previous contact with relatives with influenza-like illnesses (23.3% vs 12.5%, P = 0.042), antimicrobial use (67.4% vs 23.2%, P <0.01), and need for mechanical ventilation (25.6% vs 14.5%, P = 0.048). Patients received oseltamivir promptly. We found no differences in mortality (11.6% vs 5.2%, P = 0.076). Patients with influenza more frequently had myocarditis (9.3% vs 0.9%, P <0.01) and pericarditis (7.0% vs 0.8%, P = 0.01). Overall, 43.0% of patients (339/788) were vaccinated (51.9% of those with a clear indication [303/584]). CONCLUSION: Influenza seems to be a frequently underdiagnosed underlying condition in admissions to the C-ICU. Influenza should be screened for at C-ICU admission during influenza epidemics.


Subject(s)
Influenza, Human , Humans , Influenza, Human/diagnosis , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Prospective Studies , Seasons , Spain/epidemiology , Intensive Care Units
5.
Pathog Glob Health ; : 1-9, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37525476

ABSTRACT

Strongyloides stercoralis hyperinfection syndrome has been observed in immunosuppressed coronavirus disease 2019 (COVID-19) patients. Detecting and treating asymptomatic Strongyloides infection in individuals from endemic areas can effectively prevent hyperinfection. Unfortunately, many clinicians are unaware of this neglected infection. Therefore, we aimed to evaluate whether including Strongyloides screening in COVID-19 management protocols would encourage this practice. To accomplish this, we conducted a retrospective single-center study at 'Hospital Universitario 12 de Octubre' in Madrid, Spain, comparing two consecutive cohorts. The first cohort comprised all Latinx patients over 18 years old who were admitted for COVID-19 between March 1st and April 30th, 2020. The second cohort consisted of Latinx patients admitted between July 1st and December 31st, 2020, following an amendment to the COVID-19 management protocol that recommended screening for strongyloidiasis in at-risk patients. We identified 559 and 795 patients in the first and second periods, respectively. The percentage of individuals screened increased significantly from 8.8% to 51.6% after the screening recommendation was included in the protocol (odds ratio [OR] 11.08, 95% confidence interval [CI] 8.01-15.33). In both periods, the screening rate was significantly higher among those receiving immunosuppression than those who did not receive steroids and/or tocilizumab. No other factors influenced the screening rate. In conclusion, including strongyloidiasis screening recommendations in COVID-19 management protocols led to its increased implementation. However, the overall screening rate remained low, emphasizing the need for further efforts to enhance screening practices.

6.
J Med Virol ; 95(5): e28786, 2023 05.
Article in English | MEDLINE | ID: mdl-37212340

ABSTRACT

The aim of this study was to analyze whether the coronavirus disease 2019 (COVID-19) vaccine reduces mortality in patients with moderate or severe COVID-19 disease requiring oxygen therapy. A retrospective cohort study, with data from 148 hospitals in both Spain (111 hospitals) and Argentina (37 hospitals), was conducted. We evaluated hospitalized patients for COVID-19 older than 18 years with oxygen requirements. Vaccine protection against death was assessed through a multivariable logistic regression and propensity score matching. We also performed a subgroup analysis according to vaccine type. The adjusted model was used to determine the population attributable risk. Between January 2020 and May 2022, we evaluated 21,479 COVID-19 hospitalized patients with oxygen requirements. Of these, 338 (1.5%) patients received a single dose of the COVID-19 vaccine and 379 (1.8%) were fully vaccinated. In vaccinated patients, mortality was 20.9% (95% confidence interval [CI]: 17.9-24), compared to 19.5% (95% CI: 19-20) in unvaccinated patients, resulting in a crude odds ratio (OR) of 1.07 (95% CI: 0.89-1.29; p = 0.41). However, after considering the multiple comorbidities in the vaccinated group, the adjusted OR was 0.73 (95% CI: 0.56-0.95; p = 0.02) with a population attributable risk reduction of 4.3% (95% CI: 1-5). The higher risk reduction for mortality was with messenger RNA (mRNA) BNT162b2 (Pfizer) (OR 0.37; 95% CI: 0.23-0.59; p < 0.01), ChAdOx1 nCoV-19 (AstraZeneca) (OR 0.42; 95% CI: 0.20-0.86; p = 0.02), and mRNA-1273 (Moderna) (OR 0.68; 95% CI: 0.41-1.12; p = 0.13), and lower with Gam-COVID-Vac (Sputnik) (OR 0.93; 95% CI: 0.6-1.45; p = 0.76). COVID-19 vaccines significantly reduce the probability of death in patients suffering from a moderate or severe disease (oxygen therapy).


Subject(s)
COVID-19 , Vaccines , Humans , COVID-19 Vaccines , Oxygen , ChAdOx1 nCoV-19 , BNT162 Vaccine , Cohort Studies , Retrospective Studies , COVID-19/prevention & control , RNA, Messenger
7.
Int J Infect Dis ; 131: 173-179, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37030656

ABSTRACT

BACKGROUND: The clinical burden of influenza is increasing worldwide. Aging, immunosuppression, and underlying respiratory illness are determinants of poor clinical outcomes, including greater mortality. Bacterial infections seem to be the main reason. Updated information on the role of bacterial infection as the cause of complications would be of value in improving the prognosis of patients with influenza. METHODS: A systematic review and meta-analysis were performed by using the PubMed repository using keywords like: Influenza, H1N1, Streptococcus pneumoniae, bacterial coinfection, secondary coinfection, bacterial complications in pneumonia, and seasonal influenza. Only articles written in English were included in publications from 2010 to 2020. The analyses were conducted following the preferred reporting items for systematic review and meta-analyses guidelines. The results were independently validated using a TrinetX database cohort of roughly 4 million patients. RESULTS: We included 135 studies that contained data from 48,259 patients hospitalized with influenza of any age. Bacterial infections were diagnosed in 5391 (11.2%). Streptococcus pneumoniae (30.7%) and Staphylococcus aureus (30.4%) were the most frequent microorganisms, followed by Haemophilus influenzae (7.1%) and Pseudomonas aeruginosa (5.9%). The random-effects model of the meta-analysis indicated that bacterial infections posed a 3.4-fold increased risk of death compared with influenza infection alone. Unexpectedly, asthma was protective (odds ratio 0.8). CONCLUSION: Bacterial infections diagnosed in 11.2% of patients with influenza increase 3.4-fold the mortality risk. S. pneumoniae, S. aureus, H. influenzae, and P. aeruginosa account for nearly 75% of the cases. Earlier diagnosis and use of antibiotics should improve outcomes in this population.


Subject(s)
Coinfection , Influenza A Virus, H1N1 Subtype , Influenza, Human , Pneumonia , Staphylococcal Infections , Humans , Influenza, Human/complications , Influenza, Human/drug therapy , Influenza, Human/diagnosis , Staphylococcus aureus , Coinfection/epidemiology , Pneumonia/epidemiology , Streptococcus pneumoniae , Staphylococcal Infections/epidemiology , Haemophilus influenzae
8.
Pathog Glob Health ; 117(6): 590-595, 2023 09.
Article in English | MEDLINE | ID: mdl-36775987

ABSTRACT

Previous studies have suggested an increased susceptibility of COVID-19 among certain populations. We analyzed whether COVID-19 presentation and mortality differ between Latinx migrants and Spanish natives. METHODS AND MATERIALS: COVID-19 patients between 35-64 years old admitted between January 26th-May-5th 2020 were reviewed. Demographics, major comorbidities, symptoms, signs and analytical parameters on admission were recorded. Respiratory failure was defined as PaO2/FiO2 ≤ 200 mmHg, noninvasive or invasive mechanical ventilation requirement at any time during hospitalization. A propensity score (PS) adjustment was created between Latinx and Spanish. A multivariable logistic regression model adjusted by the PS was performed to evaluate the effects of different variables on mortality. RESULTS: 894 patients: 425 (47.5%) Latinx and 469 (52.5%) Spanish natives were included. Latinx were younger (50 vs 55 years p < 0.001) and had less comorbidities (29.4% vs 55.0% p < 0.001) than Spanish natives. More often they exhibited fever (22.1% vs 9.8% p = 0.018) and had higher inflammatory markers (PCR) (11.3 mg/dl vs 7.7 mg/dl p < 0.001). Mortality seemed lower among Latinx (4.7% vs 8.7%, p = 0.017). No association was found between ethnicity and mortality. Respiratory failure [OR = 23.978 (CI 95% 9.4-60.1) p < 0.001], LDH [OR (per unitary increment) = 1.002; CI95% (1.000-1.004;p = 0.036] and PCR [OR (per unitary increment) = 1.044 (CI95% 1.06-1.08); p = 0.02] were independently associated to mortality. CONCLUSIONS: We were unable to identify significant ethnic disparities between Latinx and Spanish natives in terms of COVID-19 mortality. Universal access to the health care system in Spain may have contributed to a better outcome of Latinx patients. Differences previously described might be a consequence of socioeconomic disparities.


Subject(s)
COVID-19 , Respiratory Insufficiency , Transients and Migrants , Adult , Humans , Middle Aged , COVID-19/epidemiology , Hispanic or Latino , Respiratory Insufficiency/epidemiology , SARS-CoV-2 , Spain
10.
Respir Res ; 23(1): 323, 2022 Nov 24.
Article in English | MEDLINE | ID: mdl-36419130

ABSTRACT

BACKGROUND: Influenza viruses cause seasonal epidemics worldwide with a significant morbimortality burden. Clinical spectrum of Influenza is wide, being respiratory failure (RF) one of its most severe complications. This study aims to elaborate a clinical prediction rule of RF in hospitalized Influenza patients. METHODS: A prospective cohort study was conducted during two consecutive Influenza seasons (December 2016-March 2017 and December 2017-April 2018) including hospitalized adults with confirmed A or B Influenza infection. A prediction rule was derived using logistic regression and recursive partitioning, followed by internal cross-validation. External validation was performed on a retrospective cohort in a different hospital between December 2018 and May 2019. RESULTS: Overall, 707 patients were included in the derivation cohort and 285 in the validation cohort. RF rate was 6.8% and 11.6%, respectively. Chronic obstructive pulmonary disease, immunosuppression, radiological abnormalities, respiratory rate, lymphopenia, lactate dehydrogenase and C-reactive protein at admission were associated with RF. A four category-grouped seven point-score was derived including radiological abnormalities, lymphopenia, respiratory rate and lactate dehydrogenase. Final model area under the curve was 0.796 (0.714-0.877) in the derivation cohort and 0.773 (0.687-0.859) in the validation cohort (p < 0.001 in both cases). The predicted model showed an adequate fit with the observed results (Fisher's test p > 0.43). CONCLUSION: we present a simple, discriminating, well-calibrated rule for an early prediction of the development of RF in hospitalized Influenza patients, with proper performance in an external validation cohort. This tool can be helpful in patient's stratification during seasonal Influenza epidemics.


Subject(s)
Influenza, Human , Lymphopenia , Respiratory Insufficiency , Adult , Humans , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Retrospective Studies , Prospective Studies , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/complications , Lymphopenia/complications , Lactate Dehydrogenases
11.
J Clin Med ; 11(20)2022 Oct 12.
Article in English | MEDLINE | ID: mdl-36294331

ABSTRACT

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been reported to increase the risk of pulmonary thromboembolism (PTE). The aim of this study is to elucidate whether Coronavirus disease COVID-19-associated PTE has a different clinical expression than non-COVID-19 PTE due to a different pathophysiology. (2) Methods: retrospective study of PTE episodes conducted at our hospital between January 2019 and December 2020, comparing the group of COVID-19-associated PTE patients with a control group of non-COVID-19 PTE patients. (3) Results: A total of 229 patients with PTE were registered, 79 of whom had COVID-19. Cancer (15.2% vs. 39.3%; p < 0.001), previous surgery (0% vs. 8%; p = 0.01), previous VTE (2.5% vs. 15.3%; p = 0.003), signs and/or symptoms of deep venous thrombosis (DVT) (7.6% vs. 22.7%; p = 0.004) and syncope (1.3% vs. 8.1%; p = 0.035) were less frequent in the COVID-19 group. Central thrombosis was more frequent in the control group (35.3% vs. 13.9%; p = 0.001). No VTE recurrent episodes were observed in the COVID-19 group, whereas four (2.7%) episodes were recorded for the control group. One-month bleeding rate was higher in the COVID-19 group (10.1% vs. 1.3%; p = 0.004). (4) Conclusion: COVID-19-associated PTE has clinical characteristics that differ from those of PTE without COVID-19, including inferior severity and a lower rate of VTE recurrence. Physicians should be aware of the high risk of bleeding in the first month of COVID-19-associated PTE.

13.
Immun Ageing ; 19(1): 38, 2022 Aug 22.
Article in English | MEDLINE | ID: mdl-35996190

ABSTRACT

BACKGROUND: Age and comorbidity are the main determinants of COVID-19 outcome. Shorter leukocyte telomere length (TL), a hallmark of biological aging, has been associated with worse COVID-19 outcomes. We sought to determine TL in patients with severe COVID-19 requiring hospitalization to analyze whether clinical outcomes and post-COVID-19 manifestations are associated with shorter TL. RESULTS: We analyzed 251 patients with PCR-confirmed COVID-19, hospitalized in the first months of the pandemics. We determined TL in PBL at admission by quantitative-PCR (qPCR) analysis in patients. A healthy cohort from the same area with a similar age range (n = 169) was used to calculate TL Z-scores. After hospital discharge, 144 COVID-19 survivors were followed-up for persistent COVID-19 manifestations. A second TL determination was performed in a smaller group of 63 patients 1 year later and compared with baseline TL. Hospitalized COVID-19 patients had a decreased baseline age-adjusted TL Z-score compared to the reference group. No differences in Z-scores were observed in patients with different COVID-19 outcomes, classified as WHO ordinal scores. In 144 patients, followed for a median of 8 months, post-COVID manifestations were not associated to differences in TL. Persistence of lung radiographic abnormalities was associated with shorter baseline TL. In patients with a second TL determination, further telomere shortening (TS) was observed in 35% and telomere lengthening in 49%. Patients with further TS had suffered a more severe disease. CONCLUSION: Shorter TL is associated with COVID-19 hospitalization but not with hospital clinical outcomes nor with persistent post-COVID-19 manifestations. Delayed resolution of radiographic lung abnormalities was also associated with shorter TL.

14.
Eur J Clin Invest ; 52(11): e13858, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35997028

ABSTRACT

BACKGROUND: Respiratory failure (RF) is the most important complication of influenza virus infection. Its definition and incidence are heterogeneous in the literature. METHODS: This systematic review and meta-analysis aim to determine the incidence of and risk factors for RF in patients hospitalized with influenza. Electronic databases were searched for articles on RF in patients hospitalized for influenza infection up to December 2021 regardless of their geographical location. Observational and experimental studies were considered for inclusion, excluding case series. The Newcastle-Ottawa and Johanna Briggs scales were used for quality assessment. A random-effects meta-analysis was performed, followed by subgroup analyses according to, among others, presence/absence of pneumonia, RF definition, serotype and time period. PRISMA guidelines were followed for this review. RESULTS: Thirty-six studies were finally included in the meta-analysis. Overall, RF incidence was 24% (range 5%-85%, 95% confidence interval [95CI] 19%-31%). Significantly higher incidences of RF were found in patients with pneumonia (42%, 95CI 28%-57%, p = .006), when RF was defined as hypoxemia (58%, 95CI 31%-81%, p < .001), and during the 2009 pandemic (25%, 95CI 16%-36%) and postpandemic period (23%, 95CI 15%-34%, p = .01). No differences were found between human influenza serotypes. Assessment of risk factors associated with the development of RF was not possible due to their inconsistent and heterogeneous reporting. CONCLUSION: Respiratory failure is frequent in hospitalized influenza patients, especially in patients with pneumonia and since the 2009 pandemic, although its definition and reporting widely vary in the literature. This complicates its characterization and comparison between cohorts and with other respiratory viruses.


Subject(s)
Influenza, Human , Pneumonia , Respiratory Insufficiency , Hospitals , Humans , Incidence , Influenza, Human/complications , Influenza, Human/epidemiology , Pneumonia/epidemiology , Respiratory Insufficiency/epidemiology , Risk Factors
15.
Int J Mol Sci ; 23(12)2022 Jun 13.
Article in English | MEDLINE | ID: mdl-35743021

ABSTRACT

NK degranulation plays an important role in the cytotoxic activity of innate immunity in the clearance of intracellular infections and is an important factor in the outcome of the disease. This work has studied NK degranulation and innate immunological profiles and functionalities in COVID-19 patients and its association with the severity of the disease. A prospective observational study with 99 COVID-19 patients was conducted. Patients were grouped according to hospital requirements and severity. Innate immune cell subpopulations and functionalities were analyzed. The profile and functionality of innate immune cells differ between healthy controls and severe patients; CD56dim NK cells increased and MAIT cells and NK degranulation rates decreased in the COVID-19 subjects. Higher degranulation rates were observed in the non-severe patients and in the healthy controls compared to the severe patients. Benign forms of the disease had a higher granzymeA/granzymeB ratio than complex forms. In a multivariate analysis, the degranulation capacity resulted in a protective factor against severe forms of the disease (OR: 0.86), whereas the permanent expression of NKG2D in NKT cells was an independent risk factor (OR: 3.81; AUC: 0.84). In conclusion, a prompt and efficient degranulation functionality in the early stages of infection could be used as a tool to identify patients who will have a better evolution.


Subject(s)
COVID-19 , Natural Killer T-Cells , Cell Degranulation , Humans , Interferon-gamma/metabolism , Killer Cells, Natural , Lymphocyte Activation
16.
Stud Health Technol Inform ; 294: 164-168, 2022 May 25.
Article in English | MEDLINE | ID: mdl-35612049

ABSTRACT

One approach to verifying the quality of research data obtained from EHRs is auditing how complete and correct the data are in comparison with those collected by manual and controlled methods. This study analyzed data quality of an EHR-derived dataset for COVID-19 research, obtained during the pandemic at Hospital Universitario 12 de Octubre. Data were extracted from EHRs and a manually collected research database, and then transformed into the ISARIC-WHO COVID-19 CRF model. Subsequently, a data analysis was performed, comparing both sources through this convergence model. More concepts and records were obtained from EHRs, and PPV (95% CI) was above 85% in most sections. In future studies, a more detailed analysis of data quality will be carried out.


Subject(s)
COVID-19 , Data Accuracy , Databases, Factual , Electronic Health Records , Humans , Pandemics
17.
Front Immunol ; 13: 878812, 2022.
Article in English | MEDLINE | ID: mdl-35547738

ABSTRACT

Introduction: There is robust evidence indicating that the SARS-CoV-2-specific humoral response is associated with protection against severe disease. However, relatively little data exist regarding how the humoral immune response at the time of hospital admission correlates with disease severity in unimmunized patients. Our goal was toidentify variables of the humoral response that could potentially serve as prognostic markers for COVID-19 progressionin unvaccinated SARS-CoV-2 patients. Methods: A prospective cross-sectional study was carried out in a cohort of 160 unimmunized, adult COVID-19 patients from the Hospital Universitario 12Octubre. Participants were classified into four clinical groups based on disease severity: non-survivors with respiratory failure (RF), RF survivors, patients requiring oxygen therapy and those not receiving oxygen therapy. Serum samples were taken on admission and IgM, IgG, IgG subclass antibody titers were determined by ELISA, and neutralizing antibody titersusing a surrogate neutralization assay. The differences in the antibody titers between groups and the association between the clinical and analytical characteristics of the patients and the antibody titers were analyzed. Results: Patients that developed RF and survived had IgM titers that were 2-fold higher than non-survivors (p = 0.001), higher levels of total IgG than those who developed RF and succumbed to infection (p< 0.001), and than patients who required oxygen therapy (p< 0.05), and had 5-fold higher IgG1 titers than RF non-survivors (p< 0.001) and those who needed oxygen therapy (p< 0.001), and 2-fold higher than patients that did not require oxygen therapy during admission (p< 0.05). In contrast, RF non-survivorshad the lowest neutralizing antibodylevels, which were significantly lower compared those with RF that survived (p = 0.03). A positive correlation was found between IgM, total IgG, IgG1 and IgG3 titers and neutralizing antibody titers in the total cohort (p ≤ 0.0036). Conclusions: We demonstrate that patients with RF that survived infection had significantly higher IgM, IgG, IgG1 and neutralizing titers compared to patients with RF that succumb to infection, suggesting that using humoral response variables could be used as a prognostic marker for guiding the clinical management of unimmunized patients admitted to the hospital for SARS-CoV-2 infection.


Subject(s)
COVID-19 , Respiratory Insufficiency , Adult , Antibodies, Neutralizing , Antibodies, Viral , Cross-Sectional Studies , Humans , Immunity, Humoral , Immunoglobulin G , Immunoglobulin M , Oxygen , Prospective Studies , Research Report , SARS-CoV-2
18.
Biomedicines ; 10(2)2022 Jan 27.
Article in English | MEDLINE | ID: mdl-35203509

ABSTRACT

The Th1/Th2 balance plays a crucial role in the progression of different pathologies and is a determining factor in the evolution of infectious diseases. This work has aimed to evaluate the early, or on diagnosis, T-cell compartment response, T-helper subsets and anti-SARS-CoV-2 antibody specificity in COVID-19 patients and to classify them according to evolution based on infection severity. A unicenter, randomized group of 146 COVID-19 patients was divided into four groups in accordance with the most critical events during the course of disease. The immunophenotype and T-helper subsets were analyzed by flow cytometry. Asymptomatic SARS-CoV-2 infected individuals showed a potent and robust Th1 immunity, with a lower Th17 and less activated T-cells at the time of sample acquisition compared not only with symptomatic patients, but also with healthy controls. Conversely, severe COVID-19 patients presented with Th17-skewed immunity, fewer Th1 responses and more activated T-cells. The multivariate analysis of the immunological and inflammatory parameters, together with the comorbidities, showed that the Th1 response was an independent protective factor for the prevention of hospitalization (OR 0.17, 95% CI 0.03-0.81), with an AUC of 0.844. Likewise, the Th1 response was found to be an independent protective factor for severe forms of the disease (OR 0.09, 95% CI: 0.01-0.63, p = 0.015, AUC: 0.873). In conclusion, a predominant Th1 immune response in the acute phase of the SARS-CoV-2 infection could be used as a tool to identify patients who might have a good disease evolution.

19.
Int J Infect Dis ; 117: 56-64, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35081417

ABSTRACT

BACKGROUND: Controversy remains about the efficacy of tocilizumab (TCZ) for the treatment of severe COVID-19. We aimed to analyze the profile of TCZ-respondent patients. METHODS: We retrospectively analyzed a cohort of patients with severe COVID-19 who received off-label TCZ after recommendation by a local committee and were admitted to the University Hospital "12 de Octubre" until May 2020. The primary end point was a significant clinical improvement (SCI) on day 14 after administration of TCZ. Factors independently related to SCI were analyzed by multivariate logistic regression models. RESULTS: Of 428 (63.3%) patients treated with TCZ, 271 (63.3%) experienced SCI. After adjustment for factors related to unfavorable outcomes, TCZ administration within the first 48 hours from admission (odds ratio [OR]: 1.98, 95% confidence Interval [95% CI]: 1.1-3.55; P = 0.02) and ALT levels >100 UI/L at day 0 (OR: 3.28; 95% CI: 1.3-8.1; P = 0.01) were independently related to SCI. The rate of SCI significantly decreased according to the time of TCZ administration: 70.2% in the first 48 hours from admission, 58.5% on days 3-7, and 45.1% after day 7 (P = 0.03 and P = 0.001, respectively). CONCLUSION: TCZ improves the prognosis of patients with COVID-19 the most if treatment starts within the first 48 hours after admission.


Subject(s)
COVID-19 Drug Treatment , Antibodies, Monoclonal, Humanized , Humans , Retrospective Studies , SARS-CoV-2
20.
PLoS One ; 17(1): e0262777, 2022.
Article in English | MEDLINE | ID: mdl-35085321

ABSTRACT

BACKGROUND: Valproic acid (VPA) has shown beneficial effects in vitro against SARS-CoV-2 infection, but no study has analyzed its efficacy in the clinical setting. METHODS: This multicenter, retrospective study included 165 adult patients receiving VPA at the time of admission to hospital, and 330 controls matched for sex, age and date of admission. A number of clinical, outcome and laboratory parameters were recorded to evaluate differences between the two groups. Four major clinical endpoints were considered: development of lung infiltrates, in-hospital respiratory worsening, ICU admissions and death. RESULTS: VPA-treated patients had higher lymphocyte (P<0.0001) and monocyte (P = 0.0002) counts, and lower levels of diverse inflammatory parameters, including a composite biochemical severity score (P = 0.016). VPA patients had shorter duration of symptoms (P<0.0001), were more commonly asymptomatic (P = 0.016), and developed less commonly lung infiltrates (65.8%/88.2%, P<0.0001), respiratory worsening (20.6%/30.6%, P = 0.019) and ICU admissions (6.1%/13.0%, P = 0.018). There was no difference in survival (84.8%/88.8%, P = 0.2), although death was more commonly related to non-COVID-19 causes in the VPA group (36.0%/10.8%, P = 0.017). The cumulative hazard for developing adverse clinical endpoints was higher in controls than in the VPA group for infiltrates (P<0.0001), respiratory worsening (P<0.0001), and ICU admissions (P = 0.001), but not for death (0.6). Multivariate analysis revealed that VPA treatment was independently protective for the development of the first three clinical endpoints (P = 0.0002, P = 0.03, and P = 0.025, respectively), but not for death (P = 0.2). CONCLUSIONS: VPA-treated patients seem to develop less serious COVID-19 than control patients, according to diverse clinical endpoints and laboratory markers.


Subject(s)
COVID-19 Drug Treatment , Valproic Acid/therapeutic use , Aged , Blood Cell Count , COVID-19/metabolism , Female , Hospitalization , Humans , Inflammation , Lung/physiopathology , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Severity of Illness Index , Spain/epidemiology , Treatment Outcome , Valproic Acid/metabolism
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