What can we learn from the blood of COVID-19 patients?

By Emily Agard

Someone's right hand wearing a blue glove is holding a vial of blood, labelled COVID-19, with images of coronavirus in the background  (Image by Fernando Zhiminaicela from Pixabay)

Coronavirus disease 2019 (COVID-19) is a global crisis with cases still on the rise while information and misinformation about it spread rapidly. Even with a doctorate in immunology, I find navigating through this pandemic is challenging. Here I break down a study that shows us what blood serum from recovered COVID-19 patients can tell us about 3 things: immunity after recovering from infection, the types of patients who produce potentially therapeutic serum, and an ideal target for vaccines.

How does the coronavirus infect humans?

Formally known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this novel virus targets primarily the lungs, but can also infect other organs such as the heart, kidneys and intestines. Certain cells of these organs have a protein, called angiotensin converting enzyme 2 (ACE2), on their surface. This ACE2 protein serves as a receptor that the virus attaches to and then uses to enter the cell, much like we use a doorknob to open a door to enter a room.

To use ACE2 as a cell entry point, SARS-CoV-2 relies on its spike protein (S protein), the characteristic feature that we see even in artistic images of the virus. Part of the spike, S1, attaches to ACE2 while another part, S2, helps to get the virus inside our cells, where it needs to be to thrive. Our cells have several copies of ACE2 on their surfaces and the virus has several spikes that it uses as keys to specifically enter these cells and disrupt their functions.

How does our body respond to the infection?

Thankfully we have an immune system that can counter viral infections. The immune response relies on the collaboration of various types of white blood cells, including B cells and different T cells. During a viral infection, B cells can make antibodies against the virus, while helper T cells regulate immune responses, and killer T cells can directly eliminate cells that are infected with the virus.

When B cells produce antibodies against the virus, we call this a humoral response. These antibodies are able to specifically recognize details on the surface of the virus, and can bind to them to neutralize the viral function and protect us from infection. Ideally our B cells maintain a memory of the infection and continue to produce these neutralizing antibodies (NAbs) that we can isolate from the serum of our blood. 

What can we learn from neutralizing antibodies in COVID-19?

Researchers in Guangzhou and Chongqing China reported how neutralizing antibodies from recovered patients varied according to the severity of their disease. These scientists examined the antibodies from 59 adult patients (30 female, 29 male, aged 33-62 years old) whose disease they classified as severe, moderate, mild or asymptomatic. They defined recovery by the absence of symptoms and 2 negative COVID tests by RT-PCR, which test  for traces of viral genetic material.

This group started by measuring the levels of specific antibodies in these patients. They looked for antibodies specific to the S1 and S2 parts of the spike protein described above, with particular focus on a special region, called the receptor binding domain (RBD) within S1. The researchers found that the more severe the patients’ disease was, the higher the levels of these antibodies in their blood.

Next, the researchers tested how well the antibodies actually functioned. They first used a pseudovirus system where they coated a harmless virus with the SARS-CoV-2 outer envelope containing the spike protein, to see if the antibodies could neutralize the pseudovirus. They found that 80% of patients who recovered from severe disease had neutralizing antibodies, while the antibodies from asymptomatic patients had no neutralizing activity, and the moderate and mild patients showed intermediate results.

With these striking results, the research team conducted further experiments using both pseudovirus and authentic virus to more closely examine the functions of the antibodies that they recovered from the 4 categories of patients. They paid particular attention to antibodies against the special RBD part of the spike protein. Serum from patients who recovered from severe or moderate disease consistently showed the strongest antiviral activity.

How can we make sense of these results?

Why do people with severe disease have the best neutralizing antibodies while asymptomatic patients have the weakest? Perhaps prolonged disease provides more opportunity for individuals to make these NAbs. Perhaps asymptomatic patients clear the infection via their T cells, without needing a strong antibody response.

This study suggests that patients who recovered from severe COVID have serum with strong therapeutic potential, while asymptomatic patients could be the most vulnerable to reinfection without a strong T cell response. It also confirms that the RBD of the virus is an ideal target for effective vaccines. Collectively these results can guide COVID treatment and prevention strategies to help us through this pandemic.