A team of researchers from Tel Aviv University and the Sharon Hospital at the Rabin Medical Center, led by Prof. Motti Gerlic and Prof. Ariel Munitz of the Department of Microbiology and Clinical Immunology at TAU’s Sackler School of Medicine, applied an innovative antibody test to about 70 COVID-19 patients at the Sharon Hospital. The researchers examined the development of antibodies targeting two different viral proteins in the patients’ bodies, and found that severely ill patients developed the antibodies at a faster rate than those with a mild case of the disease. In addition, antibodies of the type IgG were maintained in the blood of most patients throughout the study. This project has important implications for our understanding of the immune response to SARS-CoV-2, as well as future tracking of the effectiveness of vaccines and population surveys (serological tests).

A diagnostic tool

The researchers found that antibodies of the type IgM, that usually develop at the early stages of viral contagions, developed early in this case only against the protein RBD – the site at which the virus SARS-CoV-2 binds to human cells, and not against the virus’s nuclear protein. “We sampled the antibodies of about 70 COVID-19 patients at the Sharon Hospital, throughout the outbreak of the disease in Israel,” says Prof. Munitz. “Our first finding was that not all viral proteins generate a rapid immune response, but that antibodies targeting the RBD protein did develop very quickly once the symptoms appeared. This finding is quite significant, because it suggests that the test we used may be utilized as a diagnostic tool at different stages of the illness.” “The second thing we noticed, which is even more interesting, is that patients defined as severely ill developed antibodies at a faster rate than mildly ill patients, but ultimately all patients exhibited a similar immune response,” recounts Prof. Munitz. “Patients with mild, moderate and severe COVID-19 all developed the same level of antibodies. This is important, because one might have thought that the severely ill became so sick because they did not develop a sufficient amount of antibodies, and were thus unable to combat the virus effectively. We assume that the fast development of antibodies in these patients indicates that their immune system is hyper-active, but this hypothesis requires further research.”

Immunological memory

“We measured the levels of antibodies in the patients’ blood when they arrived at the hospital, during the period of hospitalization and after their release,” explains Prof. Gerlic. “We tried to understand whether the level of antibodies in their blood corresponded in any way to the severity of the illness, whether the antibodies developed in a similar way in all patients, and whether they remained in the blood for long periods of time – a critical factor for the ‘herd immunity’ we all wish to attain. We found that at later stages of the disease, about 50 days after the initial appearance of symptoms, a significant decline occurred in the presence of antibodies types IgM and IgA, regardless of the severity of the illness. In IgG-type antibodies, however, we observed only a slight decrease, even in mildly ill patients. IgG-type antibodies play an extremely important role in the immune response because they can neutralize the protein that binds the virus to human cells to enable contagion – thereby preventing the virus from penetrating the cells. We have not yet examined how the antibody actually works, and we do not know whether or not it neutralizes the virus, but the facts that these antibodies are quickly produced in all patients, and stay in the blood for a long time, suggest that they provide some level of immunity. So far, we have found that IgG-type antibodies remain in the body for two months. We will continue to monitor the patients for another year, to find out how long the antibodies remain in their bodies – hoping for the formation of an immunological memory.” In the new study the researchers from TAU used a new serological test developed in their laboratory. The IDF’s Medical Corps has already used the serological test developed by Prof. Gerlic and Prof. Munitz to detect COVID-19 antibodies in the blood of IDF soldiers. Within the next few weeks the test will be sent to the Israel’s Ministry of Health for validation, so that it may be used in population surveys. “Alongside the interesting findings,” says Prof. Munitz, “we wanted to demonstrate that our method is valid and more effective than the prevalent test for antibodies targeting viral proteins. To this end we examined samples of antibodies from the blood of COVID-19 patients, alongside samples from 200 healthy participants, taken before November 2019. We proved that our test, based on the antibodies, was able to distinguish between those who were ill and those who were not – at very high levels of sensitivity and specificity. One reason for this success is that we screen for three different antibodies: IgM that appears early and declines early, IgA – found on mucous surfaces like the lungs, and IgG, which we intend to test in the long run, because it may possibly lead to immunity.