An international team of researchers led by Dalhousie immunologists and critical care specialists in Spain has found key biomarkers in the plasma of COVID-19 patients, which will help predict the severity of illness and could lead to new treatments for the virus.
The findings, published Tuesday in the journal Critical Care, involved 250 patients with COVID-19 whose plasma was tested in Spain for the presence of ribonucleic acid or RNA, the virus’s genetic blueprint.
Dr. David Kelvin, a professor and Canada Research Chair at the Dalhousie’s Department of Microbiology and Immunology, collaborated with critical care scientists Dr. Jesus Bermejo-Martin of the Institute of Biomedical Investigation and Dr. Antoni Torres in Spain.
More than 30 research hospitals in the country were involved in assessing the viral loads in the plasma of three groups of patients with varying degrees of illness during the first wave of the pandemic wave in Spain from March 16 to April 15, 2020.
High levels of RNA
The team found that 78 percent of patients who were severely ill had higher amounts of viral RNA than those with mild cases. Those who died had the highest concentrations of viral RNA in their plasma, leading the researchers to conclude that the presence of the RNA in a patient’s blood is linked to critical illness.
Dr. Kelvin (shown left) says the research could help in quickly identifying patients at crowded hospital emergency rooms who need immediate and intensive care, and those who may be able to go home.
“We now have an extremely reliable indicator for identifying severe COVID-19 patients who require critical care and should be admitted to the ICU, which will help intensive care unit doctors prioritize severely ill patients,” says Dr. Kelvin.
Dr. Kelvin says he and his colleagues are working with a large pharmaceutical company to develop a rapid test that could produce results in 15 minutes and indicate whether a positive patient has the viral RNA and what level of care they may need. Such a device could be a valuable asset as confirmed case counts and hospitalizations continue to surge, particularly in the U.S.
In Canada, Chief Public Health Officer Dr. Theresa Tam said Tuesday that the number of people reporting severe illness was rising steadily. She added that over the last week, “there were an average of 3,020 individuals with COVID-19 being treated in Canadian hospitals, including over 600 in critical care.” Several provinces, including Ontario and Quebec, have seen sharp increases in hospitalizations in recent weeks.
“The importance of this study is that it allows identification of those patients most in need of ICU admission – all of it done by a simple blood test for presence of viral RNA,” Dr. Kelvin says.
Importantly as well, the team also discovered that the presence of COVID-19 viral RNA was directly linked to a dysfunctional immune response. That may make severe patients unable to fend off the COVID-19 infection, due in part to elevated levels of certain proteins.
The identification of these patients will also help identify those who could be treated with new therapeutics, such as antibody cocktails.
“We are also trying to figure out the why viral components are in the blood and how this leads to immune dysfunction and severe disease. Several clues are now before us and we hope to develop novel therapeutics to aid in treating severe patients,” he said.
The team used a method called droplet digital PCR to quantify the virus’s genomic material in plasma in the 50 outpatients, 100 hospitalized ward patients and 100 who were critically ill in what is believed to be the largest study of its kind using such methodology.
Patients requiring hospitalization were older than those who were discharged from the ER. Critically ill patients were more frequently male, while obesity, hypertension and type 2 diabetes were more commonly found in patients requiring hospitalization.
The novel coronavirus SARS-CoV-2, causing the new infectious coronavirus disease-2019 (COVID-19), is currently spreading rapidly around the world; it has been recently declared as a pandemic by WHO. Recent clinical observation suggests that patient age, male sex and certain chronic medical conditions (e.g., cardiovascular disease, diabetes, COPD) seem to represent a risk for the infection of SARS-Cov-2 and higher disease severity1.
There is currently no biological marker known to predict the susceptibility to COVID-19. Landsteiner’s ABO blood types are carbohydrate epitopes that are present on the surface of human cells. The antigenic determinants of A and B blood groups are trisaccharide moieties GalNAcα1-3-(Fucα1,2)-Galβ- and Galα1-3-(Fucα1,2)-Galβ-, while O blood group antigen is Fucα1,2-Galβ-. While blood types are genetically inherited, the environment factors can potentially influence which blood types in a population will be passed on more frequently to the next generation.
Susceptibility of viral infection has been previously found to be related to ABO blood group. For example, Norwalk virus and Hepatitis B have clear blood group susceptibility2,3. It was also reported that blood group O individuals were less likely to become infected by SARS coronavirus4. Here, we investigated the relationship between the ABO blood type and the susceptibility to COVID-19 in patients from three hospitals in Wuhan and Shenzhen, China to test if the former may be a biomarker for the latter.
In this study, we found that ABO blood groups displayed different association risks for the infection with SARS-CoV-2 resulting in COVID-19. Specifically, blood group A was associated with an increased risk whereas blood group O was associated with a decreased risk, thus demonstrating that the ABO blood type is a biomarker for differential susceptibility of COVID-19.
These findings are consistent with similar risk patterns of ABO blood groups for other coronavirus infection found in previous studies. For example, Cheng et al. reported that the SARS-CoV infection susceptibility in Hong Kong was differentiated by the ABO blood group systems4.
The authors found that compared with non-O blood group hospital staff, blood group O hospital staff had a lower chance of getting infected. Patrice et al. found that anti-A antibodies specifically inhibited the adhesion of SARS-CoV S protein-expressing cells to ACE2-expressing cell lines7.
Given the nucleic acid sequence similarity8 and receptor angiotensin-converting enzyme 2 (ACE2) binding similarity between SARS-CoV and SARS-CoV-29-11, the lower susceptibility of blood group O and higher susceptibility of blood group A for COVID-19 could be linked to the presence of natural anti-blood group antibodies, particularly anti-A antibody, in the blood. This speculation will need direct studies to prove. There may also be other mechanisms underlying the ABO blood group-differentiated susceptibility for COVID-19 that require further studies to elucidate.
reference link: https://www.medrxiv.org/content/10.1101/2020.03.11.20031096v2.full-text
More information: Jesús F. Bermejo-Martin et al. Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19, Critical Care (2020). DOI: 10.1186/s13054-020-03398-0