The COVID-19 viral load at ICU admission determines patient prognosis

A new study reveals the importance of the 'viral storm' in critical patients with COVID-19. The study has been published in The Lancet Microbe and conducted by several groups in the area of respiratory diseases (CIBERES) and the area of infectious diseases (CIBERINFEC) at the CIBER, a consortium from the Institute of Health Carlos III (ISCIII). The results show that the viral load at ICU admission is a factor that determines the prognosis of critical patients with COVID-19.

The CIBER researchers who led the study - part of the CIBERESUCICOVID project of the COVID Fund - Instituto de Salud Carlos III - Antoni Torres, Ferrán Barbé, Jesús Bermejo, Anna Motos and Salvador Resino, together with Nadia García-Mateo (IBSAL) and David J. Kelvin of Dalhousie University (Canada), observed that the higher the plasma viral RNA load in patients with COVID-19 on admission to the ICU, the higher the risk of mortality.

The territorial clinical director of chronic respiratory diseases, professor at the University of Lleida and head of the Translational Research in Respiratory Medicine group, Ferrán Barbé, scientific director of CIBERES, says it will be important "to study what impact this viral storm has on the long-term consequences of the disease in critical patients who survived the virus".

Specifically, a group of patients were identified who presented a 'viral storm', characterised by the massive release of SARS-CoV-2 ribonucleic acid (RNA) and proteins in the blood, and who, on admission to the ICU, had not produced sufficient antibodies against the S protein of the virus, showing signs of an increased inflammatory response. This group represents one-third of the 836 critically ill patients with COVID-19 from a cohort recruited during the first year of the pandemic in 23 ICUs across the country. Not only did they have the highest mortality rate (half died within 90 days of admission), but they also had significant complications: 94% required invasive mechanical ventilation, 41% suffered acute renal failure and 65% developed secondary infections.

Thus, it is shown that patients with COVID-19 who are unable to control the virus have the worst prognosis, and that the inflammatory response in these patients is directly related to the intensity of viral replication. It is revealed that the key to preventing complications of COVID-19 in patients with risk factors lies in early control of the virus, a fundamental principle that could be applied not only to future pandemics caused by emerging viruses, but also to viruses responsible for seasonal epidemics.

This is where the "main value of the study" lies, in the words of Jesús Bermejo, principal investigator of CIBERES belonging to the Biomedical Research Institute of Salamanca and the Río Hortega University Hospital of Valladolid, "it helps us to better understand the true primary cause of severe COVID-19, which is the inability of some patients to control the virus, demonstrated by the passage of large amounts of viral material into the blood. These are patients who, because of their advanced age or the presence of other diseases such as diabetes, have difficulty producing antibodies (and probably cell-mediated immunity) against the virus.

The project, led by CIBERES together with the Instituto de Investigación Biomédica de Salamanca, the Hospital Clínic de Barcelona and the Institut de Recerca Biomèdica de Lleida, has involved a great multidisciplinary effort in which more than 80 intensivists and translational researchers from 23 ICUs throughout Spain have collaborated, including experts from the CIBER de Enfermedades Infecciosas (CIBERINFEC).

The study used state-of-the-art technologies funded by CIBERES and the Instituto de Salud Carlos III (ISCIII), such as the QX200 digital PCR and SimplePlex biomarker quantification platforms.

Vaccination, key to reducing the 'viral storm'

Antoni Torres, principal investigator of CIBERES belonging to the Pneumology Service of the Hospital Clínic de Barcelona, says that "the results demonstrate the importance of vaccination, especially in frail patients, as well as early treatment with antivirals when these patients are infected, in order to prevent them from developing this 'viral storm'". However, there are patients who, because they are immunosuppressed, do not respond well to vaccines and "in them we have to implement active strategies of early treatment with antivirals, to avoid this intensity of viral replication".

THE CYBERESUCICOVID PROJECT

The CIBERESUCICOVID study, led by the researcher Antoni Torres, group leader of the CIBER of Respiratory Diseases (CIBERES) of the ISCIII at the Hospital Clinic of Barcelona, determines the risk factors and prognosis of patients infected with COVID-19 who are admitted to Spanish Intensive Care Units (ICU) from the beginning of the pandemic in Spain until the end of the pandemic.
The study is possible thanks to the aid that the CIBER received from the COVID-19 Fund, which was granted by the ISCIII to support research projects that will improve the clinical approach to COVID-19. In addition, the CIBERES-ICU-COVID plus project, funded by ISCIII-UNESPA, which aims to identify the molecular factors associated with poor prognosis and long-term complications in these patients, also contributed to this work.

Article: Jesús F Bermejo-Martin, Nadia García-Mateo, Anna Motos, Salvador Resino, Luis Tamayo, Pablo Ryan Murua, Elena Bustamante-Munguira, Elena Gallego Curto, Alejandro Úbeda-Iglesias, María del Carmen de la Torre, Ángel Estella, Sandra Campos-Fernández et al. Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study. The Lancet Microbe. 2023 Apr 25. DOI: https://doi.org/10.1016/S2666-5247(23)00041-1