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Article ; Online: Mortality and renal long-term outcome of critically ill COVID-19 patients with acute kidney failure, continuous renal replacement therapy and invasive mechanical ventilation.

Melero, Rosa / Mijaylova, Antonia / Rodríguez-Benítez, Patrocinio / García-Prieto, Ana / Cedeño, Jamil / Goicoechea, Marian

Medicina clinica (English ed.)

2022 Volume 159, Issue 11, Page(s) 529–535

Abstract: Background: There are limited data describing the long-term renal outcomes of critically ill COVID-19 patients with acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) and invasive mechanical ventilation.: Methods: In this ... ...

Abstract	Background: There are limited data describing the long-term renal outcomes of critically ill COVID-19 patients with acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) and invasive mechanical ventilation. Methods: In this retrospective observational study we analyzed the long-term clinical course and outcomes of 30 critically ill patients hospitalized with COVID-19 during the peak of highest incidence in the first wave, with acute respiratory distress syndrome (ARDS) and AKI that required CRRT. Baseline features, clinical course, laboratory data, therapies and filters used in CRRT were compared between survivors and non-survivors to identify risk factors associated with in-hospital death. Renal parameters: glomerular filtration rate, proteinuria and microhematuria were collected at 6 months after discharge. Results: 19 patients (63%) died and 11 were discharged. Mean time to death was 48 days (7-206) after admission. Patients with worse baseline renal function had higher mortality ( Conclusion: Mortality among critically ill hospitalized patients diagnosed with COVID-19 on CRRT is extremely high (63%). Baseline renal function is a predictor factor of mortality. Filters with adsorption capacity did not modify survival. None survivor patients required long-term dialysis, but an important loss of renal function occurred after AKI episode related to COVID-19 infection.
Language	English
Publishing date	2022-07-07
Publishing country	Spain
Document type	Journal Article
ISSN	2387-0206
ISSN (online)	2387-0206
DOI	10.1016/j.medcle.2022.02.015
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Article ; Online: Mortality and renal long-term outcome of critically ill COVID-19 patients with acute kidney failure, continuous renal replacement therapy and invasive mechanical ventilation.

Melero, Rosa / Mijaylova, Antonia / Rodríguez-Benítez, Patrocinio / García-Prieto, Ana / Cedeño, Jamil / Goicoechea, Marian

Medicina clinica

2022 Volume 159, Issue 11, Page(s) 529–535

Title translation	Mortalidad y función renal a largo plazo en pacientes ingresados en la UCI por COVID-19 con fracaso renal agudo, terapia continua de reemplazo renal y ventilación mecánica invasiva.
Abstract	Background: There are limited data describing the long-term renal outcomes of critically ill COVID-19 patients with acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) and invasive mechanical ventilation. Methods: In this retrospective observational study we analyzed the long-term clinical course and outcomes of 30 critically ill patients hospitalized with COVID-19 during the peak of highest incidence in the first wave, with acute respiratory distress syndrome (ARDS) and AKI that required CRRT. Baseline features, clinical course, laboratory data, therapies and filters used in CRRT were compared between survivors and non-survivors to identify risk factors associated with in-hospital death. Renal parameters: glomerular filtration rate, proteinuria and microhematuria were collected at 6months after discharge. Results: 19 patients (63%) died and 11 were discharged. Mean time to death was 48days (7-206) after admission. Patients with worse baseline renal function had higher mortality (P=.009). Patients were treated with CRRT for an average of 18.4days. Filters with adsorptive capacity (43%) did not offer survival benefits. Regarding long-term renal outcomes, survivor patients did not receive any additional dialysis, but 9 out of 11 patients had an important loss of renal function (median of eGF of 44 (13-76)ml/min/1.73m Conclusion: Mortality among critically ill hospitalized patients diagnosed with COVID-19 on CRRT is extremely high (63%). Baseline renal function is a predictor factor of mortality. Filters with adsorption capacity did not modify survival. None survivor patients required long-term dialysis, but an important loss of renal function occurred after AKI episode related to COVID-19 infection.
MeSH term(s)	Humans ; Critical Illness/therapy ; Continuous Renal Replacement Therapy ; Hospital Mortality ; Respiration, Artificial ; COVID-19/complications ; COVID-19/therapy ; Acute Kidney Injury/therapy ; Retrospective Studies ; Kidney/physiology ; Renal Replacement Therapy
Language	Spanish
Publishing date	2022-04-26
Publishing country	Spain
Document type	Observational Study ; Journal Article
ZDB-ID	411607-0
ISSN	1578-8989 ; 0025-7753
ISSN (online)	1578-8989
ISSN	0025-7753
DOI	10.1016/j.medcli.2022.02.014
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Article ; Online: COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital.

Ramos, Rafael / de la Villa, Sofía / García-Ramos, Sergio / Padilla, Belén / García-Olivares, Pablo / Piñero, Patricia / Garrido, Alberto / Hortal, Javier / Muñoz, Patricia / Caamaño, Estrela / Benito, Pilar / Cedeño, Jamil / Garutti, Ignacio

Enfermedades infecciosas y microbiologia clinica (English ed.)

2023 Volume 41, Issue 5, Page(s) 278–283

Abstract: Introduction: Our work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant ... ...

Abstract	Introduction: Our work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. Methods: Retrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. Results: Two-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p<0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4-16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1-5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2-5.1, p<0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p<0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). Conclusions: Superinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.
MeSH term(s)	Humans ; Retrospective Studies ; Tertiary Care Centers ; Superinfection/drug therapy ; COVID-19/complications ; COVID-19/epidemiology ; Intensive Care Units ; Sepsis/drug therapy ; Anti-Bacterial Agents/therapeutic use
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2023-05-02
Publishing country	Spain
Document type	Journal Article
ISSN	2529-993X
ISSN (online)	2529-993X
DOI	10.1016/j.eimce.2021.10.013
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Article ; Online: COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital.

Enfermedades infecciosas y microbiologia clinica

2021 Volume 41, Issue 5, Page(s) 278–283

Abstract	Introduction: Our work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. Methods: Retrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48 h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. Results: Two-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, Conclusions: Superinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.
Language	English
Publishing date	2021-11-20
Publishing country	Spain
Document type	Journal Article
ZDB-ID	1070941-1
ISSN	1578-1852 ; 0213-005X
ISSN (online)	1578-1852
ISSN	0213-005X
DOI	10.1016/j.eimc.2021.10.014
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Article: Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients.

Romero-Cristóbal, Mario / Clemente-Sánchez, Ana / Piñeiro, Patricia / Cedeño, Jamil / Rayón, Laura / Del Río, Julia / Ramos, Clara / Hernández, Diego-Andrés / Cova, Miguel / Caballero, Aranzazu / Garutti, Ignacio / García-Olivares, Pablo / Hortal, Javier / Guerrero, Jose-Eugenio / García, Rita / Bañares, Rafael / Rincón, Diego

Therapeutic advances in gastroenterology

2021 Volume 14, Page(s) 17562848211023410

Abstract: Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has ... ...

Abstract	Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. Methods: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan-Meier and Cox regression analysis. Results: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) Conclusion: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.
Language	English
Publishing date	2021-06-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2440710-0
ISSN	1756-2848 ; 1756-283X
ISSN (online)	1756-2848
ISSN	1756-283X
DOI	10.1177/17562848211023410
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Article: Long-term survival of mechanically ventilated patients with severe COVID-19: an observational cohort study.

Peñuelas, Oscar / Del Campo-Albendea, Laura / de Aledo, Amanda Lesmes González / Añón, José Manuel / Rodríguez-Solís, Carmen / Mancebo, Jordi / Vera, Paula / Ballesteros, Daniel / Jiménez, Jorge / Maseda, Emilio / Figueira, Juan Carlos / Franco, Nieves / Algaba, Ángela / Avilés, Juan Pablo / Díaz, Ricardo / Abad, Beatriz / Canabal, Alfonso / Abella, Ana / Gordo, Federico /

García, Javier / Suarez, Jessica García / Cedeño, Jamil / Martínez-Palacios, Basilia / Manteiga, Eva / Martínez, Óscar / Blancas, Rafael / Bardi, Tommaso / Pestaña, David / Lorente, José Ángel / Muriel, Alfonso / Esteban, Andrés / Frutos-Vivar, Fernando

Annals of intensive care

2021 Volume 11, Issue 1, Page(s) 143

Abstract: Background: Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and undergoing invasive mechanical ventilation. We aimed ...

Abstract	Background: Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and undergoing invasive mechanical ventilation. We aimed to estimate 180-day mortality of patients with COVID-19 requiring invasive ventilation, and to develop a predictive model for long-term mortality. Methods: Retrospective, multicentre, national cohort study between March 8 and April 30, 2020 in 16 intensive care units (ICU) in Spain. Participants were consecutive adults who received invasive mechanical ventilation for COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in positive testing of a nasopharyngeal sample and confirmed by real time reverse-transcriptase polymerase chain reaction (rt-PCR). The primary outcomes was 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model was developed to estimate the probability of 180-day mortality. Results: 868 patients were included (median age, 64 years [interquartile range [IQR], 56-71 years]; 72% male). Severity at ICU admission, estimated by SAPS3, was 56 points [IQR 50-63]. Prior to intubation, 26% received some type of noninvasive respiratory support. The unadjusted overall 180-day survival rates was 59% (95% CI 56-62%). The predictive factors measured during ICU stay, and associated with 180-day mortality were: age [Odds Ratio [OR] per 1-year increase 1.051, 95% CI 1.033-1.068)), SAPS3 (OR per 1-point increase 1.027, 95% CI 1.011-1.044), diabetes (OR 1.546, 95% CI 1.085-2.204), neutrophils to lymphocytes ratio (OR per 1-unit increase 1.008, 95% CI 1.001-1.016), failed attempt of noninvasive positive pressure ventilation prior to orotracheal intubation (OR 1.878 (95% CI 1.124-3.140), use of selective digestive decontamination strategy during ICU stay (OR 0.590 (95% CI 0.358-0.972) and administration of low dosage of corticosteroids (methylprednisolone 1 mg/kg) (OR 2.042 (95% CI 1.205-3.460). Conclusion: The long-term survival of mechanically ventilated patients with severe COVID-19 reaches more than 50% and may help to provide individualized risk stratification and potential treatments. Trial registration: ClinicalTrials.gov Identifier: NCT04379258. Registered 10 April 2020 (retrospectively registered).
Language	English
Publishing date	2021-10-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2617094-2
ISSN	2110-5820
ISSN	2110-5820
DOI	10.1186/s13613-021-00929-y
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Article: Renal long-term outcome of critically ill COVID-19 patients with acute kidney failure and continuous renal replacement therapy.

Melero, Rosa / Mijaylova, Antonia / Rodriguez-Benitez, Patrocinio / Macías, Nicolas / Aragoncillo, Ines / Rodriguez-Ferrero, Maria Luisa / Garcia-Prieto, Ana / Bascuñana, Arturo / Acosta, Adriana / Gonzalez-Rojas, Angela / de Morales, Alejandra Muñoz / Carbayo, Javier / Sanchez-Cámara, Luis / Verdalles, Ursula / Abad, Soraya / Vega, Almudena / Verde, Eduardo / Arroyo, David / de Jose, Ana Perez /

Piñero, Patricia / Cedeño, Jamil / Anaya, Fernando / Rengel, Manuel Antonio / Barraca, Daniel / Olmedo, María / Goicoechea, Marian

Clinical kidney journal

2021 Volume 14, Issue 11, Page(s) 2449–2450

Language	English
Publishing date	2021-08-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2655800-2
ISSN	2048-8513 ; 2048-8505
ISSN (online)	2048-8513
ISSN	2048-8505
DOI	10.1093/ckj/sfab150
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Article ; Online: Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients.

Martin-Vicente, María / Almansa, Raquel / Martínez, Isidoro / Tedim, Ana P / Bustamante, Elena / Tamayo, Luis / Aldecoa, César / Gómez, José Manuel / Renedo, Gloria / Berezo, Jose Ángel / Cedeño, Jamil Antonio / Mamolar, Nuria / García Olivares, Pablo / Herrán-Monge, Rubén / Cicuendez, Ramón / Enríquez, Pedro / Ortega, Alicia / Jorge, Noelia / Doncel, Cristina /

Journal of internal medicine

2021 Volume 291, Issue 2, Page(s) 232–240

Abstract: Background: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID ...

Abstract	Background: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. Patients/methods: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. Results: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). Conclusions: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.
MeSH term(s)	Antibodies, Viral/blood ; Antigens, Viral/blood ; COVID-19/immunology ; COVID-19/mortality ; Critical Illness ; Humans ; RNA, Viral/blood ; SARS-CoV-2
Chemical Substances	Antibodies, Viral ; Antigens, Viral ; RNA, Viral
Language	English
Publishing date	2021-10-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	96274-0
ISSN	1365-2796 ; 0954-6820
ISSN (online)	1365-2796
ISSN	0954-6820
DOI	10.1111/joim.13386
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Article ; Online: Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients

Martin-Vicente, Maria / Almansa, Raquel / Martinez, Isidoro / Tedim, Ana P. / Bustamante, Elena / Tamayo, Luis / Aldecoa, Cesar / Gomez, Jose Manuel / Renedo, Gloria / Berezo, Jose Angel / Cedeno, Jamil Antonio / Mamolar, Nuria / Garcia Olivares, Pablo / Herran, Ruben / Cicuendez, Ramon / Enriquez, Pedro / Ortega, Alicia / Jorge, Noelia / de la Fuente, Amanda /

Bustamante-Munguira, Juan / Munoz-Gomez, Maria Jose / Gonzalez-Rivera, Milagros / Puertas, Carolina / Mas, Vicente / Vazquez, Monica / Perez-Garcia, Felipe / Rico-Feijoo, Jesus / Martin, Silvia / Motos, Anna / Fernandez-Barat, Laia / Eiros, Jose Maria / Dominguez-Gil, Marta / Ferrer, Ricard / Barbe, Ferran / Kelvin, David / Bermejo-Martin, Jesus F / Resino, Salvador / Torres, Antoni

medRxiv

Abstract: Purpose: to evaluate the association between anti-SARS-CoV-2 S IgM and IgG antibodies with viral RNA load in plasma, the frequency of antigenemia and with the risk of mortality in critically ill patients with COVID-19. Methods: anti-SARS-CoV-2 S ... ...

Abstract	Purpose: to evaluate the association between anti-SARS-CoV-2 S IgM and IgG antibodies with viral RNA load in plasma, the frequency of antigenemia and with the risk of mortality in critically ill patients with COVID-19. Methods: anti-SARS-CoV-2 S antibodies levels, viral RNA load and antigenemia were profiled in plasma of 92 adult patients in the first 24 hours following ICU admission. The impact of these variables on 30-day mortality was assessed by using Kaplan-Meier curves and multivariate Cox regression analysis. Results: non survivors showed more frequently absence of anti-SARS-CoV-2 S IgG and IgM antibodies than survivors (26.3% vs 5.6% for IgM and 18.4% vs 5.6% for IgG), and a higher frequency of antigenemia (47.4% vs 22.2%) (p <0.05). Non survivors showed lower concentrations of anti-S IgG and IgM and higher viral RNA loads in plasma, which were associated to increased 30-day mortality and decreased survival mean time. [Adjusted HR (CI95%), p]: [S IgM (AUC ≥60): 0.48 (0.24; 0.97), 0.040]; [S IgG (AUC ≥237): 0.47 (0.23; 0.97), 0.042]; [Antigenemia (+): 2.45 (1.27; 4.71), 0.007]; [N1 viral load (≥ 2.156 copies/mL): 2.21 (1.11; 4.39),0.024]; [N2 viral load (≥ 3.035 copies/mL): 2.32 (1.16; 4.63), 0.017]. Frequency of antigenemia was >2.5-fold higher in patients with absence of antibodies. Levels of anti-SARS-CoV-2 S antibodies correlated inversely with viral RNA load. Conclusion: absence / insufficient levels of anti-SARS-CoV-2 S antibodies following ICU admission is associated to poor viral control, evidenced by increased viral RNA loads in plasma, higher frequency of antigenemia, and also to increased 30-day mortality.
Keywords	covid19
Language	English
Publishing date	2021-03-08
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.03.08.21253121
Database	COVID19

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Article ; Online: Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19.

Bermejo-Martin, Jesús F / González-Rivera, Milagros / Almansa, Raquel / Micheloud, Dariela / Tedim, Ana P / Domínguez-Gil, Marta / Resino, Salvador / Martín-Fernández, Marta / Ryan Murua, Pablo / Pérez-García, Felipe / Tamayo, Luis / Lopez-Izquierdo, Raúl / Bustamante, Elena / Aldecoa, César / Gómez, José Manuel / Rico-Feijoo, Jesús / Orduña, Antonio / Méndez, Raúl / Fernández Natal, Isabel /

Megías, Gregoria / González-Estecha, Montserrat / Carriedo, Demetrio / Doncel, Cristina / Jorge, Noelia / Ortega, Alicia / de la Fuente, Amanda / Del Campo, Félix / Fernández-Ratero, José Antonio / Trapiello, Wysali / González-Jiménez, Paula / Ruiz, Guadalupe / Kelvin, Alyson A / Ostadgavahi, Ali Toloue / Oneizat, Ruth / Ruiz, Luz María / Miguéns, Iria / Gargallo, Esther / Muñoz, Ioana / Pelegrin, Sara / Martín, Silvia / García Olivares, Pablo / Cedeño, Jamil Antonio / Ruiz Albi, Tomás / Puertas, Carolina / Berezo, Jose Ángel / Renedo, Gloria / Herrán, Rubén / Bustamante-Munguira, Juan / Enríquez, Pedro / Cicuendez, Ramón / Blanco, Jesús / Abadia, Jesica / Gómez Barquero, Julia / Mamolar, Nuria / Blanca-López, Natalia / Valdivia, Luis Jorge / Fernández Caso, Belén / Mantecón, María Ángeles / Motos, Anna / Fernandez-Barat, Laia / Ferrer, Ricard / Barbé, Ferrán / Torres, Antoni / Menéndez, Rosario / Eiros, José María / Kelvin, David J

Critical care (London, England)

2020 Volume 24, Issue 1, Page(s) 691

Abstract: Background: COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied ...

Abstract	Background: COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods: A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. Results: The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183-12.968], 0.025), viral RNA load (N1) (1.962 [1.244-3.096], 0.004); viral RNA load (N2) (2.229 [1.382-3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). Conclusions: SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.
MeSH term(s)	Adult ; Aged ; Biomarkers/analysis ; Biomarkers/blood ; COVID-19/blood ; COVID-19/complications ; Chi-Square Distribution ; Critical Illness ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Polymerase Chain Reaction/methods ; RNA, Viral/analysis ; RNA, Viral/blood ; Statistics, Nonparametric ; Viral Load/immunology
Chemical Substances	Biomarkers ; RNA, Viral
Language	English
Publishing date	2020-12-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041406-7
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/s13054-020-03398-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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