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 (CIBERINEC) 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 study was led by Antoni Torres, senior consultant in the Pulmonology Service at the Hospital Clínic, head of the IDIBAPS Applied research in infectious respiratory diseases and critically ill patients group and principal investigator at CIBERES where he coordinates the CIBERUCISCOVID project and Anna Motos, form the same research group; Jesús Bermejo, principal investigator at CIBERES belonging to the Institute of Biomedical Research of Salamanca and the University Hospital Río Hortega in Valladolid; Ferrán Barbé, scientific director of CIBERES belonging to the Institute of Biomedical Research of Lleida (IRBLleida); and Salvador Resino, from the National Microbiology Center – Institute of Health Carlos III (ISCIII); together with Nadia García-Mateo (IBSAL) and David J. Kelvin (Dalhousie University de Canadá).
The researchers observed that the higher the viral RNA load in plasma in patients with COVID-19 at ICU admission, the greater the risk of mortality. More specifically, a group of patients was observed presenting a ‘viral storm’, characterized by the massive release of ribonucleic acid (RNA) and SARS-CoV-2 proteins into the blood, and that, at ICU admission, they had not produced enough antibodies against the S protein of the virus, showing signs of a greater inflammatory response.
This group represents a third of the 836 critically ill patients with COVID-19 in a cohort recruited during the first year of the pandemic in 23 ICUs across Spain. These patients not only presented a higher mortality rate (half of them died in the first 90 days after admission), they also had significant complications: 94% of them required invasive mechanical ventilation, 41% suffered acute renal failure and 65% developed secondary infections.
So, this shows that patients with COVID-19 who are unable to control the virus are those with the poorest prognosis, and the inflammatory response in these patients is directly related to the intensity of the viral replication. It has been shown that the key to preventing complications of COVID-19 in patients with risk factors lies in the 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 at CIBERES, belonging to the Institute of Biomedical Research of Salamanca and the Hospital Río Hortega in Valladolid, “it helps us gain a better understanding of the true primary cause of severe COVID-19, which is the inability of some patients to control the virus, shown by the release of large quantities 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 difficulties in producing antibodies (and probably cellular immunity) against the virus".
Vaccination, key to reducing the 'viral storm’
Antoni Torres, principal investigator at CIBERES, belonging to the Pulmonology Service at the Hospital Clínic de Barcelona, states that, “the results show the importance of vaccination, especially in fragile patients, as well as early treatment with antivirals when these patients are infected, in order to prevent them developing this 'viral storm'". However, there are patients who, because they are immunosuppressed, do not respond well to vaccines and “with them we have to implement active early treatment strategies with antivirals, in order to avoid this intense viral replication”.
Ferrán Barbé, scientific director of CIBERES, belonging to the Institute of Biomedical Research of Lleida (IRBLleida) adds that, “it will also be important to study what impact this viral storm has on the long-term consequences of the disease in critically ill patients who survived the virus".
The study involved a great multidisciplinary effort with the collaboration of over 80 intensivists and translational researchers from 23 ICUs across Spain, including experts from the CIBER of Infectious Diseases (CIBERINFEC).
For the study, state-of-the-art technologies were used, funded by CIBERES and by the Carlos III Health Institute (ISCIII), as well as the QX200 digital PCR and Simple Plex biomarker quantification platforms.
The CIBERESUCICOVID project
The CIBERESUCICOVID study, led by researcher Antoni Torres, has been determining the risk factors and the prognosis of patients infected with COVID-19 admitted to Spanish Intensive Care Units (ICUs) since the start of the pandemic in Spain, and will continue until it ends.
The study was made possible thanks to the aid CIBER received from the COVID-19 Fund, which was granted by the Carlos III Health Institute (ISCIII) to support research projects that will improve the clinical approach to COVID-19. Moreover, the CIBERES-UCI-COVID project funded by SCIII-UNESPA, which seeks to identify the molecular factors associated with poor prognosis and long-term complications in these patients, also contributed to this work.
Study reference:
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
