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1.
Am J Transplant ; 20(7): 1849-1858, 2020 07.
Article Dans Anglais | MEDLINE | ID: covidwho-2270901

Résumé

The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after solid organ transplant (SOT) remain unknown. We report our preliminary experience with 18 SOT (kidney [44.4%], liver [33.3%], and heart [22.2%]) recipients diagnosed with COVID-19 by March 23, 2020 at a tertiary-care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon-ß (16.7%). As of April 4, the case-fatality rate was 27.8% (5/18). After a median follow-up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C-reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS-CoV-2 infection has a severe course in SOT recipients.


Sujets)
Infections à coronavirus/complications , Infections à coronavirus/mortalité , Infections à coronavirus/thérapie , Transplantation d'organe , Pneumopathie virale/complications , Pneumopathie virale/mortalité , Pneumopathie virale/thérapie , Receveurs de transplantation , Sujet âgé , Antiviraux/administration et posologie , Betacoronavirus , COVID-19 , Association médicamenteuse , Femelle , Fièvre , Humains , Hydroxychloroquine/administration et posologie , Immunosuppresseurs/administration et posologie , Immunosuppresseurs/effets indésirables , Interféron bêta/administration et posologie , Lopinavir/administration et posologie , Mâle , Adulte d'âge moyen , Pandémies , Radiographie thoracique , Études rétrospectives , Ritonavir/administration et posologie , SARS-CoV-2 , Espagne/épidémiologie
2.
Clin Transplant ; 37(6): e14966, 2023 06.
Article Dans Anglais | MEDLINE | ID: covidwho-2264765

Résumé

Pyogenic liver abscess (PLA) is a life-threatening infection in both liver transplant (LT) and non-LT patients. Several risk factors, such as benign and malignant hepatopancreatobiliary diseases and colorectal tumors have been associated with PLA in the non-LT population, and hepatic artery stricture/thrombosis, biliary stricture, and hepaticojejunostomy in the LT patients. The objective of this study is to compare the outcomes of patients with PLA in LT and non-LT patients and to determine the risk factors associated with patient survival. From January 2000 to November 2020, a total of 296 adult patients were diagnosed of PLA in our institution, of whom 26 patients had previously undergone liver transplantation (LTA group), whereas 263 patients corresponded to the non-LTA population. Seven patients with PLA who had undergone previous kidney transplantation were excluded from this retrospective study. Twenty-six patients out of 1503 LT developed PLA (incidence of 1.7%). Median age was significantly higher in non-LTA patients (p = .001). No significant differences were observed in therapy. PLA recurrence was significantly higher in LTA than in non-LTA (34.6% vs. 14.8%; p = .008). In-hospital mortality was greater in the LT group than in the non-LT group (19.2% vs. 9.1% p = .10) and was identified in multivariable analysis as a risk factor for mortality (p = .027). Mortality rate during follow-up did not show significant differences between the groups: 34.6% in LTA patients versus 26.2% in non-LTA patients (p = .10). The most common causes of mortality during follow-up were malignancies, Covid-19 infection, and neurologic disease. 1-, 3-, and 5-year actuarial patient survival rates were 87.0%, 64.1%, and 50.4%, respectively, in patients of LTA group, and 84.5%, 66.5%, and 51.0%, respectively, in patients with liver abscesses in non-LTA population (p = .53). In conclusion, LT was a risk factor for in hospital mortality, but not during long-term follow-up.


Sujets)
COVID-19 , Abcès hépatique à pyogènes , Transplantation hépatique , Adulte , Humains , Abcès hépatique à pyogènes/étiologie , Abcès hépatique à pyogènes/thérapie , Études rétrospectives , Transplantation hépatique/effets indésirables , Sténose pathologique/étiologie , COVID-19/étiologie , Facteurs de risque
3.
Pulm Circ ; 12(4): e12142, 2022 Oct.
Article Dans Anglais | MEDLINE | ID: covidwho-2068581

Résumé

The coronavirus 2019 disease (COVID-19) pandemic threatened the Spanish health-care system. Patients with demanding conditions such as precapillary pulmonary hypertension (PH) faced a potentially severe infection, while their usual access to medical care was restricted. This prospective, unicentric study assessed the impact of COVID-19 on PH patients' outcomes and the operational changes in the PH network. Sixty-three PH patients (41 pulmonary arterial hypertension [PAH]; 22 chronic thromboembolic pulmonary hypertension [CTEPH]) experienced COVID-19. Overall mortality was 9.5% without differences when stratifying by hemodynamics or PAH-risk score. Patients who died were older (73.6 ± 5 vs. 52.2 ± 15.4; p = 0.001), with more comorbidities (higher Charlson index: 4.17 ± 2.48 vs. 1.14 ± 1.67; p = 0.0002). Referrals to the PH expert center decreased compared to the previous 3 years (123 vs. 160; p = 0.002). The outpatient activity shifted toward greater use of telemedicine. Balloon pulmonary angioplasty activity could be maintained after the first pandemic wave and lockdown while pulmonary thromboendarterectomy procedures decreased (19 vs. 36; p = 0.017). Pulmonary transplantation activity remained similar. The COVID-19 mortality in PAH/CTEPH patients was not related to hemodynamic severity or risk stratification, but to comorbidities. The pandemic imposed structural changes but a planned organization and resource reallocation made it possible to maintain PH patients' care.

4.
Pulmonary circulation ; 12(4), 2022.
Article Dans Anglais | EuropePMC | ID: covidwho-2057927

Résumé

The coronavirus 2019 disease (COVID‐19) pandemic threatened the Spanish health‐care system. Patients with demanding conditions such as precapillary pulmonary hypertension (PH) faced a potentially severe infection, while their usual access to medical care was restricted. This prospective, unicentric study assessed the impact of COVID‐19 on PH patients' outcomes and the operational changes in the PH network. Sixty‐three PH patients (41 pulmonary arterial hypertension [PAH];22 chronic thromboembolic pulmonary hypertension [CTEPH]) experienced COVID‐19. Overall mortality was 9.5% without differences when stratifying by hemodynamics or PAH‐risk score. Patients who died were older (73.6 ± 5 vs. 52.2 ± 15.4; p = 0.001), with more comorbidities (higher Charlson index: 4.17 ± 2.48 vs. 1.14 ± 1.67; p = 0.0002). Referrals to the PH expert center decreased compared to the previous 3 years (123 vs. 160;p = 0.002). The outpatient activity shifted toward greater use of telemedicine. Balloon pulmonary angioplasty activity could be maintained after the first pandemic wave and lockdown while pulmonary thromboendarterectomy procedures decreased (19 vs. 36; p = 0.017). Pulmonary transplantation activity remained similar. The COVID‐19 mortality in PAH/CTEPH patients was not related to hemodynamic severity or risk stratification, but to comorbidities. The pandemic imposed structural changes but a planned organization and resource reallocation made it possible to maintain PH patients' care.

7.
Front Immunol ; 13: 878812, 2022.
Article Dans Anglais | MEDLINE | ID: covidwho-1933661

Résumé

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.


Sujets)
COVID-19 , Insuffisance respiratoire , Adulte , Anticorps neutralisants , Anticorps antiviraux , Études transversales , Humains , Immunité humorale , Immunoglobuline G , Immunoglobuline M , Oxygène , Études prospectives , Rapport de recherche , SARS-CoV-2
8.
Medicina clinica (English ed.) ; 158(12):608-612, 2022.
Article Dans Anglais | EuropePMC | ID: covidwho-1904679

Résumé

Background The effect of immunomodulatory therapy with tocilizumab for coronavirus disease 2019 (COVID-19) in real-life clinical practice remains controversial. Methods Single-center retrospective matched cohort analysis including 47 consecutive patients treated with intravenous tocilizumab for severe COVID-19 pneumonia (“TCZ group”), matched by age, comorbidities, time from symptoms onset and baseline SpO2/FiO2 ratio with 47 patients receiving standard of care alone (“SoC group”). Results There were no significant differences between the TCZ and SoC groups in the rate of clinical improvement (hospital discharge and/or a decrease of ≥2 points on a six-point ordinal scale) by day 7 (51.1% [24/47] versus 48.9% [23/47];P-value = 1.000). No differences were observed at day 14 in terms of clinical improvement (72.3% versus 76.6%;P-value = 0.791), all-cause mortality (10.6% versus 12.8%;P-value = 1.000), and the composite of invasive mechanical ventilation and/or death (25.5% versus 23.4%;P-value = 1.000) either. Patients in the TCZ group had a more rapid normalization of C-reactive protein levels. Conclusions No apparent benefit was observed in patients with severe COVID-19 treated with tocilizumab as compared to a matched retrospective cohort.

9.
Int J Infect Dis ; 117: 56-64, 2022 Apr.
Article Dans Anglais | MEDLINE | ID: covidwho-1654570

Résumé

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.


Sujets)
, Anticorps monoclonaux humanisés , Humains , Études rétrospectives , SARS-CoV-2
10.
Transplant Direct ; 7(12): e794, 2021 Dec.
Article Dans Anglais | MEDLINE | ID: covidwho-1528247

Résumé

Severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) elicited by mRNA-based vaccines in solid organ transplant (SOT) recipients and its correlation with antibody responses remain poorly characterized. METHODS: We included 44 (28 kidney, 14 liver, and 2 double organ) recipients who received the full series of the mRNA-1273 vaccine. SARS-CoV-2-CMI was evaluated at baseline, before the second dose, and at 2 wk after completion of vaccination by an ELISpot-based interferon-γ FluoroSpot assay using overlapping peptides covering the S1 domain. SARS-CoV-2 immunoglobulin G seroconversion and serum neutralizing activity against the spike protein were assessed at the same points by commercial ELISA and an angiotensin-converting enzyme-2/spike antibody inhibition method, respectively. Postvaccination SARS-CoV-2-CMI was compared with 28 healthcare workers who received the BNT162b2 vaccine. RESULTS: Positive SARS-CoV-2-CMI increased from 6.8% at baseline to 23.3% after the first mRNA-1273 dose and 59.5% after the completion of vaccination (P < 0.0001). Lower rates were observed for immunoglobulin G seroconversion (2.3%, 18.6%, and 57.1%, respectively) and neutralizing activity (2.3%, 11.6%, and 31.0%). There was a modest correlation between neutralizing titers and the magnitude of SARS-CoV-2-CMI (Spearman's rho: 0.375; P = 0.015). Fifteen recipients (35.7%) mounted SARS-CoV-2-CMI without detectable neutralizing activity, whereas 3 (7.1%) did the opposite, yielding poor categorical agreement (Kappa statistic: 0.201). Rates of positive SARS-CoV-2-CMI among SOT recipients were significantly decreased compared with nontransplant controls (82.1% and 100.0% after the first dose and completion of vaccination, respectively; P < 0.0001). Kidney transplantation, the use of tacrolimus and prednisone, and the number of immunosuppressive agents were associated with lower cell-mediated responses. Results remained unchanged when 3 recipients with prevaccination SARS-CoV-2-CMI were excluded. CONCLUSIONS: Two-thirds of SOT recipients mounted SARS-CoV-2-CMI following vaccination with mRNA-1273. Notable discordance was observed between vaccine-induced cell-mediated and neutralizing humoral immunities. Future studies should determine whether these patients with incomplete responses are effectively protected.

13.
Med Clin (Barc) ; 158(12): 608-612, 2022 06 24.
Article Dans Anglais, Espagnol | MEDLINE | ID: covidwho-1303631

Résumé

BACKGROUND: The effect of immunomodulatory therapy with tocilizumab for coronavirus disease 2019 (COVID-19) in real-life clinical practice remains controversial. METHODS: Single-center retrospective matched cohort analysis including 47 consecutive patients treated with intravenous tocilizumab for severe COVID-19 pneumonia ("TCZ group"), matched by age, comorbidities, time from symptoms onset and baseline SpO2/FiO2 ratio with 47 patients receiving standard of care alone ("SoC group"). RESULTS: There were no significant differences between the TCZ and SoC groups in the rate of clinical improvement (hospital discharge and/or a decrease of ≥2 points on a six-point ordinal scale) by day 7 (51.1% [24/47] versus 48.9% [23/47]; P-value=1.000). No differences were observed at day 14 in terms of clinical improvement (72.3% versus 76.6%; P-value=0.791), all-cause mortality (10.6% versus 12.8%; P-value=1.000), and the composite of invasive mechanical ventilation and/or death (25.5% versus 23.4%; P-value=1.000) either. Patients in the TCZ group had a more rapid normalization of C-reactive protein levels. CONCLUSIONS: No apparent benefit was observed in patients with severe COVID-19 treated with tocilizumab as compared to a matched retrospective cohort.


Sujets)
, SARS-CoV-2 , Anticorps monoclonaux humanisés , Humains , Études rétrospectives , Résultat thérapeutique
14.
Am J Transplant ; 21(8): 2785-2794, 2021 08.
Article Dans Anglais | MEDLINE | ID: covidwho-1258890

Résumé

Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2-specific T cell-mediated immunity (SARS-CoV-2-CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS-CoV-2-CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)-γ FluoroSpot assay after a median of 103 days from COVID-19 diagnosis. Serum SARS-CoV-2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post-transplant SARS-CoV-2-CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN-γ-producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike-specific and nucleoprotein-specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein-specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike-specific IFN-γ-producing SFUs and time from diagnosis (Spearman's rho: -0.418; p value = .024). Two recipients (6.5%) failed to mount either T cell-mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable-but declining over time-SARS-CoV-2-CMI after a median of 3 months from COVID-19, with no meaningful differences with immunocompetent patients.


Sujets)
COVID-19 , Transplantation hépatique , Anticorps antiviraux , Dépistage de la COVID-19 , Humains , Transplantation hépatique/effets indésirables , SARS-CoV-2 , Lymphocytes T , Receveurs de transplantation
15.
Transplantation ; 105(6): 1372-1380, 2021 06 01.
Article Dans Anglais | MEDLINE | ID: covidwho-1249353

Résumé

BACKGROUND: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown. METHODS: We enumerated SARS-CoV-2-specific interferon-γ-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6. RESULTS: Detectable (≥0.1%) SARS-CoV-2-specific CD4+ T-cell response was found in 57.1% and 47.4% of patients at months 4 and 6. Corresponding rates for CD8+ T cells were 19.0% and 42.1%, respectively. Absolute SARS-CoV-2-specific T-cell counts increased from month 4 to month 6 in CD8+ (P = 0.086) but not CD4+ subsets (P = 0.349). Four of 10 patients with any detectable response at month 4 had lost SARS-CoV-2-CMI by month 6, whereas 5 of 9 patients mounted SARS-CoV-2-CMI within this period. All but 2 patients (89.5%) tested positive for SARS-CoV-2 IgG. Patients lacking detectable SARS-CoV-2-specific CD4+ response by month 6 were more likely to be under tacrolimus (100.0% versus 66.7%; P = 0.087) and to have received tocilizumab for the previous COVID-19 episode (40.0% versus 0.0%; P = 0.087). CONCLUSIONS: Although still exploratory and limited by small sample size, the present study suggests that a substantial proportion of KT recipients exhibited detectable SARS-CoV-2-CMI after 6 months from COVID-19 diagnosis.


Sujets)
COVID-19/immunologie , Immunité cellulaire , Sujet immunodéprimé , Transplantation rénale/effets indésirables , SARS-CoV-2/immunologie , Adulte , Sujet âgé , Anticorps monoclonaux humanisés/administration et posologie , Anticorps monoclonaux humanisés/effets indésirables , Lymphocytes T CD4+/immunologie , Lymphocytes T CD4+/métabolisme , Lymphocytes T CD8+/immunologie , Lymphocytes T CD8+/métabolisme , COVID-19/sang , COVID-19/diagnostic , Dépistage de la COVID-19 , Femelle , Études de suivi , Rejet du greffon/immunologie , Rejet du greffon/prévention et contrôle , Humains , Immunosuppresseurs/effets indésirables , Interféron gamma/métabolisme , Mâle , Adulte d'âge moyen , Receveurs de transplantation ,
16.
J Med Virol ; 93(2): 831-842, 2021 02.
Article Dans Anglais | MEDLINE | ID: covidwho-1206798

Résumé

Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-ß (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia.


Sujets)
Anticorps monoclonaux humanisés/usage thérapeutique , Antiviraux/usage thérapeutique , , Syndrome de libération de cytokines/prévention et contrôle , Facteurs immunologiques/usage thérapeutique , SARS-CoV-2/pathogénicité , Administration par voie intraveineuse , Adulte , Température du corps/effets des médicaments et des substances chimiques , Protéine C-réactive/métabolisme , COVID-19/immunologie , COVID-19/mortalité , COVID-19/virologie , Syndrome de libération de cytokines/immunologie , Syndrome de libération de cytokines/mortalité , Syndrome de libération de cytokines/virologie , Femelle , Rythme cardiaque/effets des médicaments et des substances chimiques , Humains , Interféron bêta/effets indésirables , L-Lactate dehydrogenase/sang , Mâle , Adulte d'âge moyen , Récepteurs à l'interleukine-6/antagonistes et inhibiteurs , Récepteurs à l'interleukine-6/génétique , Récepteurs à l'interleukine-6/immunologie , Fréquence respiratoire/effets des médicaments et des substances chimiques , Études rétrospectives , SARS-CoV-2/immunologie , Indice de gravité de la maladie , Analyse de survie
17.
Expert Opin Biol Ther ; 21(4): 431-434, 2021 04.
Article Dans Anglais | MEDLINE | ID: covidwho-1189386
18.
Int J Infect Dis ; 105: 487-494, 2021 Apr.
Article Dans Anglais | MEDLINE | ID: covidwho-1108327

Résumé

BACKGROUND: The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. METHODS: A retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400-600mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. RESULTS: Totals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17-0.68; P=0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21-0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21-0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49-3.41; P<0.001). The occurrence of secondary infection was similar between both groups. CONCLUSIONS: The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19.


Sujets)
Anticorps monoclonaux humanisés/administration et posologie , , Méthylprednisolone/administration et posologie , SARS-CoV-2 , Sujet âgé , Sujet âgé de 80 ans ou plus , Association de médicaments , Femelle , Humains , Mâle , Adulte d'âge moyen , Études rétrospectives
19.
Int J Infect Dis ; 105: 319-325, 2021 Apr.
Article Dans Anglais | MEDLINE | ID: covidwho-1081278

Résumé

OBJECTIVES: A subgroup of patients with SARS-CoV-2 infection was thought to have developed cytokine release syndrome and were treated with tocilizumab; however, a significant percentage of patients evolved. This study aimed to determine the usefulness of anakinra as a rescue treatment for patients with tocilizumab-refractory COVID-19 disease. METHODS: A prospective cohort of patients with COVID-19 pneumonia who received anakinra as salvage therapy after failure of tocilizumab were compared (1:1) with selected controls in a historical cohort of patients treated with tocilizumab. Cases and controls were matched by age, comorbidities, pulse oximetry oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at baseline, and time elapsed since the initiation of treatment with tocilizumab. The primary outcome was the improvement in clinical status measured by a 6-point ordinal scale, from baseline to day 21. RESULTS: The study included 20 cases and 20 controls (mean age 65.3 ± 12.8 years, 65% males). No differences were found in the clinical improvement rates at 7, 14 and 21 days of follow-up. The in-hospital mortality rate for patients receiving anakinra was 55% vs. 45% in the control group (P = 0.527). CONCLUSIONS: Treatment with anakinra was not useful in improving the prognosis of patients with tocilizumab-refractory severe COVID-19.


Sujets)
Anticorps monoclonaux humanisés/usage thérapeutique , , Syndrome de libération de cytokines/traitement médicamenteux , Antagoniste du récepteur à l'interleukine-1/usage thérapeutique , SARS-CoV-2 , Sujet âgé , COVID-19/complications , Études cas-témoins , Études de cohortes , Syndrome de libération de cytokines/étiologie , Femelle , Mortalité hospitalière , Humains , Immunomodulation/effets des médicaments et des substances chimiques , Mâle , Adulte d'âge moyen , Études rétrospectives , Thérapie de rattrapage , Espagne/épidémiologie , Échec thérapeutique , Résultat thérapeutique
20.
Eur J Clin Microbiol Infect Dis ; 40(6): 1209-1216, 2021 Jun.
Article Dans Anglais | MEDLINE | ID: covidwho-1012224

Résumé

The aim of our study was to elucidate if SARS-CoV-2 viral load on admission, measured by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) cycle threshold (Ct) value on nasopharyngeal samples, was a marker of disease severity. All hospitalized adult patients with a diagnosis of SARS-CoV-2 infection by rRT-PCR performed on a nasopharingeal sample from March 1 to March 18 in our institution were included. The study population was divided according to the Ct value obtained upon admission in patients with high viral load (Ct < 25), intermediate viral load (Ct: 25-30) and low viral load (Ct > 30). Demographic, clinical and laboratory variables of the different groups were analyzed to assess the influence of viral load on the development of respiratory failure during admission. Overall, 455 sequential patients were included. The median Ct value was 28 (IQR: 24-32). One hundred and thirty patients (28.6%) had a high viral load, 175 (38.5%) an intermediate viral load and 150 (33%) a low viral load. Advanced age, male sex, presence of cardiovascular disease and laboratory markers such as lactate dehydrogenase, lymphocyte count and C-reactive protein, as well as a high viral load on admission, were predictive of respiratory failure. A Ct value < 25 was associated with a higher risk of respiratory failure during admission (OR: 2.99, 95%IC: 1.57-5.69). SARS-CoV-2 viral load, measured through the Ct value on admission, is a valuable tool to predict the development of respiratory failure in COVID-19 inpatients.


Sujets)
COVID-19/complications , Insuffisance respiratoire/virologie , Charge virale , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , COVID-19/diagnostic , Détection de l'acide nucléique du virus de la COVID-19 , Femelle , Hospitalisation , Humains , Mâle , Adulte d'âge moyen , Partie nasale du pharynx/virologie , Réaction de polymérisation en chaine en temps réel
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