This is a summary, written by members of the CITF Secretariat, of:

Brunet-Ratnasingham E, Anand SP, Gantner P, Dyachenko A, Moquin-Beaudry G, Brassard N, et al. Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality. Sci Adv. 2021 Nov 26;7(48):eabj5629. doi: 10.1126/sciadv.abj5629.

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

CITF-funded researchers Drs. Daniel Kaufmann, Andrés Finzi and Nicolas Chomont from the Université de Montréal and the Université de Montréal hospital research centre (CRCHUM), along with their collaborators, found that the amount of viral mRNA  in the blood can help identify hospitalized patients who will suffer severe COVID-19, and even death. The discovery of molecular markers to help identify individuals at risk of severe disease could contribute to determining early preventive measures for improved patient outcomes. The manuscript is published in Science Advances.

Many studies report advanced age and comorbidities as risk factors for severe COVID-19 disease, but there is also a wide range of molecular abnormalities associated with severe infection. From a clinical perspective, this becomes challenging as there is a need for a minimal set of blood markers that can be easily and rapidly used to identify the patients that are most at risk. The research team tested the amount of SARS-CoV-2 RNA present in the blood, levels of antibodies targeting the virus, and cytokines (small proteins that are involved in immune cell signaling), as well as tissue and lung injury markers to see if they were associated with increased mortality. Patients were clinically followed for 60 days after symptom onset.

Key findings:

  • The amount of SARS-CoV-2 virus in the blood was strongly associated with disease severity and mortality.
  • There were overall higher cytokine levels in the blood of COVID-19 patients with severe disease compared with the non-severe group. These included pro-inflammatory cytokines including IL-6, GM-CSF, and TNFα.
  • Markers of lung and vascular damage including RAGE and angiopoietin-2  increased with disease severity. These markers were also found to be positively correlated with the amount of virus present.
  • Using an antibody-antigen assay, researchers found no difference in the levels of SARS-CoV-2 IgM, IgA and IgG antibodies between the severe and non-severe groups.
  • Further assessment of SARS-CoV-2 antibodies revealed higher IgG antibodies and antibodies involved in Fc-mediated effector functions, associated with increased survival.

In this study, researchers collected blood samples from 217 hospitalized patients, 11 days after the onset of COVID-19 symptoms. Some of these patients were in critical care requiring ventilation, while others had less severe infections.

Using regression analysis, each of the identified biomarkers was measured to determine if they could be used to predict mortality. The amount of virus, certain tissue injury markers, and cytokine levels were found to be associated with an increased risk of mortality.

Taken together, these findings suggest that measuring the amount of vRNA in the blood can help identify patients at high risk of mortality, informing robust medical attention and treatments.