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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.
  • Bermejo-Martin JF; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • González-Rivera M; Hospital Universitario Río Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Almansa R; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, 3-5, 28029, Madrid, Spain.
  • Micheloud D; Department of Laboratory Medicine, Hospital General Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain.
  • Tedim AP; Department of Medicine, Faculty of Medicine, Universidad Complutense de Madrid, Plaza de Ramón y Cajal, s/n, 28040, Madrid, Spain.
  • Domínguez-Gil M; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • Resino S; Hospital Universitario Río Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Martín-Fernández M; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, 3-5, 28029, Madrid, Spain.
  • Ryan Murua P; Emergency Department, Hospital General Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain.
  • Pérez-García F; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • Tamayo L; Hospital Universitario Río Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Lopez-Izquierdo R; Microbiology Service, Hospital Universitario Rio Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Bustamante E; Viral Infection and Immunity Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. de Pozuelo, 28, 28222, Majadahonda, Spain.
  • Aldecoa C; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • Gómez JM; Hospital Universitario Río Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Rico-Feijoo J; Hospital Universitario Infanta Leonor, Av. Gran Vía del Este, 80, 28031, Madrid, Spain.
  • Orduña A; Servicio de Microbiología Clínica, Hospital Universitario Príncipe de Asturias, Carr. de Alcalá, s/n, 28805, Madrid, Spain.
  • Méndez R; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • Fernández Natal I; Intensive Care Unit, Hospital Universitario Rio Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Megías G; Emergency Department, Hospital Universitario Rio Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • González-Estecha M; Intensive Care Unit, Hospital Clínico Universitario de Valladolid, Av. Ramón y Cajal, 47003, Valladolid, Spain.
  • Carriedo D; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • Doncel C; Department of Anesthesiology, Facultad de Medicina de Valladolid, Av. Ramón y Cajal, 47005, Valladolid, Spain.
  • Jorge N; Anesthesiology and Reanimation Service, Hospital Universitario Rio Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Ortega A; Intensive Care Unit, Hospital General Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain.
  • de la Fuente A; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • Del Campo F; Anesthesiology and Reanimation Service, Hospital Universitario Rio Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Fernández-Ratero JA; Microbiology Service, Hospital Clinico Universitario de Valladolid, Av. Ramón y Cajal, 47003, Valladolid, Spain.
  • Trapiello W; Pulmonology Service, Hospital Universitario y Politécnico de La Fe, Avinguda de Fernando Abril Martorell, 106, 46026, Valencia, Spain.
  • González-Jiménez P; Clinical Microbiology Department, Complejo Asistencial Universitario de León, Calle Altos de Nava, s/n, 24001, León, Spain.
  • Ruiz G; Microbiology Service, Hospital Universitario de Burgos, Av. Islas Baleares, 3, 09006, Burgos, Spain.
  • Kelvin AA; Department of Laboratory Medicine, Hospital General Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain.
  • Ostadgavahi AT; Department of Medicine, Faculty of Medicine, Universidad Complutense de Madrid, Plaza de Ramón y Cajal, s/n, 28040, Madrid, Spain.
  • Oneizat R; Intensive Care Unit, Complejo Asistencial Universitario de León, Calle Altos de nava, s/n, 24001, León, Spain.
  • Ruiz LM; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • Miguéns I; Hospital Universitario Río Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Gargallo E; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, 3-5, 28029, Madrid, Spain.
  • Muñoz I; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • Pelegrin S; Hospital Universitario Río Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Martín S; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, 3-5, 28029, Madrid, Spain.
  • García Olivares P; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • Cedeño JA; Hospital Universitario Río Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Ruiz Albi T; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, 3-5, 28029, Madrid, Spain.
  • Puertas C; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca, (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
  • Berezo JÁ; Hospital Universitario Río Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Renedo G; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Av. de Monforte de Lemos, 3-5, 28029, Madrid, Spain.
  • Herrán R; Pneumology Service, Hospital Universitario Río Hortega/Biomedical Engineering Group, Universidad de Valladolid, Calle Dulzaina, 2, 47012, Valladolid, Spain.
  • Bustamante-Munguira J; Intensive Care Unit, Hospital Universitario de Burgos, Av. Islas Baleares, 3, 09006, Burgos, Spain.
  • Enríquez P; Clinical Analysis Service. Hospital, Clínico Universitario de Valladolid, Av. Ramón y Cajal, 47003, Valladolid, Spain.
  • Cicuendez R; Pulmonology Service, Hospital Universitario y Politécnico de La Fe, Avinguda de Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Crit Care ; 24(1): 691, 2020 12 14.
Article in English | MEDLINE | ID: covidwho-977684
Semantic information from SemMedBD (by NLM)
1. Critical Illness COEXISTS_WITH COVID-19
Subject
Critical Illness
Predicate
COEXISTS_WITH
Object
COVID-19
2. Dysregulated host response COEXISTS_WITH COVID-19
Subject
Dysregulated host response
Predicate
COEXISTS_WITH
Object
COVID-19
3. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
4. Nucleoproteins PART_OF 2019 novel coronavirus
Subject
Nucleoproteins
Predicate
PART_OF
Object
2019 novel coronavirus
5. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
6. Critical Illness AFFECTS Patients
Subject
Critical Illness
Predicate
AFFECTS
Object
Patients
7. chemokine STIMULATES Natural Killer Cells
Subject
chemokine
Predicate
STIMULATES
Object
Natural Killer Cells
8. Plasma ASSOCIATED_WITH Severe (severity modifier)
Subject
Plasma
Predicate
ASSOCIATED_WITH
Object
Severe (severity modifier)
9. Critical Illness COEXISTS_WITH COVID-19
Subject
Critical Illness
Predicate
COEXISTS_WITH
Object
COVID-19
10. Dysregulated host response COEXISTS_WITH COVID-19
Subject
Dysregulated host response
Predicate
COEXISTS_WITH
Object
COVID-19
11. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
12. Nucleoproteins PART_OF 2019 novel coronavirus
Subject
Nucleoproteins
Predicate
PART_OF
Object
2019 novel coronavirus
13. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
14. Critical Illness AFFECTS Patients
Subject
Critical Illness
Predicate
AFFECTS
Object
Patients
15. chemokine STIMULATES Natural Killer Cells
Subject
chemokine
Predicate
STIMULATES
Object
Natural Killer Cells
16. Plasma ASSOCIATED_WITH Severe (severity modifier)
Subject
Plasma
Predicate
ASSOCIATED_WITH
Object
Severe (severity modifier)
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Viral / Viral Load / COVID-19 Type of study: Risk factors Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Crit Care Year: 2020 Document Type: Article Affiliation country: S13054-020-03398-0

Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Viral / Viral Load / COVID-19 Type of study: Risk factors Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Crit Care Year: 2020 Document Type: Article Affiliation country: S13054-020-03398-0