Breaking Down COVID-19

EDITOR’S NOTE: Julia Brodt is a microbiologist with 12 years of medical research experience and 22 years teaching in higher education who, along with her husband, John K. Hall, MD, is a member of the RACmonitor Editorial Board and a recurring special guest on Monitor Mondays. This is the first segment in her new series taking a deep dive into the known clinical and medical facts of COVID-19.

The virus SARS-CoV-2, known for causing COVID-19, is a novel coronavirus that took the U.S by surprise. The first case entered the country in mid-January 2020, and just seven months later, current COVID deaths are currently nearing 170,000.

Treatments act to support patients who test positive for the disease, as there is no vaccine. A recent study by investigators at Harvard, MIT, the Ragon Institute of MGH, and the University of Washington School of Medicine found that five immune markers in serum were able to distinguish which SARS-CoV-2-positive patients were likely to convalesce, and which patients would not survive. As patients exhibit a range of symptoms, this information could be useful for determining an earlier prognosis to indicate supportive treatments or reveal possible targets for vaccine production.

The SARS-CoV-2 virus is comprised of several key components, including its genetic material, a single positive strand of ribonucleic acid (RNA) linked with nucleoproteins (N), a covering of protein and membrane (M), and spikes (S) that protrude away from anchors in the spherical envelope. A segment on Monitor Mondays airing on Aug. 10 presented background information about the structure and function of human antibodies. The viral S proteins permit virus attachment to host cells via a cell membrane protein, angiotensin-converting enzyme 2, or ACE2, which is found on many cell types in humans, namely those lining body passages like digestive and respiratory tracts. Once the virus attaches itself, it fuses with the host cell membrane, the RNA enters the cell, and it hijacks the cell machinery and makes copies of itself to infect other host cells.

Galit Alter, co-author of the group study “COVID-19 Patients Exhibit Early Antibody Signatures Predictive of Death or Recovery,” stated that a goal of the project was to examine the immune profile of positive patients, after which “we can begin to truly understand how the immune system responds to COVID-19, then use that knowledge to prevent the worst outcomes of this disease.”

It is thought that coronaviruses replicate in human hosts, even though some patients may remain asymptomatic, while others sicken and die. To determine a disease trajectory, more understanding of antibody production is needed. A test group of 22 patients hospitalized for COVID-19 provided samples for testing. Using 60 assays, detailed immune profiles were created. Of these 22 patients, 12 recovered, while 10 did not survive. It had been shown that viruses make more N protein than S protein within the host, but interestingly, those who survived had produced a stronger immune response to the S protein, whereas those who died generated more antibodies to the N protein. Furthermore, the antibodies could be characterized as IgM and IgA1, produced in the S protein survivors, and IgM and IgA2, along with complement (serum proteins involved in inflammation) generated against the N protein in non-survivors. This data was confirmed in a follow-up of 40 patients, 20 survivors and 20 who died.

Based upon their antibody status, these COVID-19 patient profiles identified who would make it and who would not. This information presents an approach to determine patients at risk for severe sequelae and those in diminished danger for death. This data opens doors to potential treatments.