Could previous exposure to the common cold viruses affect the severity of symptoms of SARS-CoV-2?

Universitätsmedizin Berlin and the Max Planck Institute for Molecular Genetics (MPIMG) show that some healthy people have immune cells capable of recognizing the new coronavirus, SARS-CoV-2. The reason for this could be found in previous infections with the ‘common cold’ coronavirus. The ‘Charité Corona Cross’ study will address whether or not this cross-reactivity has a protective effect on the clinical course in individuals infected with SARS-CoV-2.

Why do some people develop severe symptoms after infection with the new coronavirus, while others hardly notice the infection? The answer to this question is multi-layered and is the subject of intense research. A team of researchers from Charité and the MPIMG have identified a potentially crucial factor: previous exposure to harmless coronaviruses from the “common cold.” This information is based on the research of T-helper cells, a specialized type of white blood cell that is essential for the regulation of our immune response. The researchers found that one in three people without prior exposure to SARS-CoV-2, however, has T-helper cells capable of recognizing the virus. The probable reason for this is that SARS-CoV-2 shares certain structural similarities with coronaviruses that are responsible for the common cold.

For their study, the researchers isolated immune cells from the blood of 18 COVID-19 patients who received treatment in Charité and confirmed positive PCR for SARS-CoV-2. They also isolated immune cells from the blood of 68 healthy individuals who had never been exposed to the new coronavirus. The researchers then stimulated these immune cells using small synthetic fragments of SARS-CoV-2 ‘spike proteins’, the characteristic corona-like bumps on the outer surface of coronaviruses that allow the virus to enter human cells. The researchers subsequently tested whether T-helper cells would be activated by contact with these protein fragments. They found that this was the case in 15 of 18 patients with COVID-19 (85%). “This was exactly what we expected. The immune system of these patients was in the process of fighting this new virus and therefore showed the same reaction in vitro,” explains one of the study’s three main authors, Dr. Claudia. Giesecke-Thiel. , head of the flow cytometry installation at the MPIMG. She adds, “The fact that not all COVID-19 patients showed this helper T cell response to viral fragments is probably due to the fact that T cells cannot be activated outside of the human body during an acute phase or particularly serious illness. “

However, the team was surprised to find memory helper T cells capable of recognizing SARS-CoV-2 fragments in the blood of healthy individuals. They were found in a total of 24 of 68 healthy individuals evaluated (35%). In fact, the researchers noted that the immune cells of the COVID-19 patients reacted to different fragments of the viral envelope than the immune cells of healthy individuals. While the T-helper cells of the patients recognized the spike protein in its entire length, the T-helper cells isolated from healthy individuals were mainly activated by sections of the spike protein that showed similarity to the corresponding sections found in the proteins. Spike of harmless’ common cold coronaviruses. “This suggests that T-helper cells from healthy individuals react to SARS-CoV-2 due to prior exposure to the endemic ‘common cold’ coronavirus,” says Dr. Giesecke-Thiel. She goes on to explain: “One of the characteristics of T-helper cells is that they are activated not only by a pathogen with an” exact fit, “but also by pathogens with” sufficient similarity. “In particular, the researchers were able to demonstrate that the T-helper cells isolated from healthy participants who reacted to SARS-CoV-2 were also activated by various ‘common cold’ coronaviruses, which show what is known as ‘cross reactivity’.

The effects of this cross-reactivity in a previously healthy person infected with SARS-CoV-2 were not addressed in the current study. “Generally speaking, it is possible that cross-reaction helper T cells have a protective effect, for example, by helping the immune system to speed up its production of antibodies against the new virus,” explains co-author Dr Leif Erik. Sander of the Charité Medical Department, Division of Infectious Diseases and Respiratory Medicine. He adds: “In this case, a recent episode of the common cold would likely result in less severe symptoms of COVID-19. However, it is also possible that cross-reactive immunity may lead to a misdirected immune response and potentially negative effects on the COVID-19 clinical course. We know this can occur with dengue fever, for example. “

Prospective studies will be needed to conclusively determine whether previous coronavirus infections of the “common cold” confer protection against subsequent infection with SARS-CoV-2, and whether this could explain the high variability in clinical manifestations. One of these studies has just been launched, which will be led by Charité and carried out in collaboration with the Technische Universität Berlin and the MPIMG. Funded by the Federal Ministry of Health (BMG) and the Federal Institute for Drugs and Medical Devices (BfArM), the ‘Charité Corona Crossover Study’ will investigate the impact of cross-reaction helper T cells on the COVID-19 course.

In Germany, coronaviruses are responsible for up to 30 percent of all seasonal colds, says Professor Dr. Andreas Thiel, a Charité researcher based at Si-M (‘Der Simulierte Mensch, literally’ The simulated human ‘, a joint research space of Charité and Technische Universität Berlin) and the BIH Center for Regenerative Therapies (BCRT). “Current estimates suggest that the average adult will contract an infection caused by one of the four endemic coronaviruses approximately every two to three years,” explains Professor Thiel, who is the paper’s third senior co-author and responsible for coordinating the Cruz Charité Corona. Study. And he adds: “If we assume that these cold viruses are capable of conferring a certain level of immunity against SARS-CoV-2, this would mean that people who have had frequent exposure to such infections in the past and who test positive for Auxiliary reactive T-cell crosses should have better protection. Therefore, this group of people will be a particular focus of the ‘Charité Corona Cross Study’. ” The researchers will simultaneously monitor COVID-19 at-risk populations for several months. Ultimately, the study aims to help predict the clinical course of COVID-19, both in people with and without previous SARS-CoV-2 infections. “This is of utmost importance, both in terms of people’s daily lives and the treatment of patients,” explains Professor Thiel.

The study includes a comprehensive immunological investigation of childcare staff, pediatric practice staff, and nursing home residents, which will last until next year. Swabs collected from participants will be evaluated for SARS-CoV-2 using PCR-based tests. Additional tests will include tests for virus antibodies and T-cell reactivity. If the study participants subsequently contract SARS-CoV-2, the researchers will be able to establish links between the course of the disease and the immune parameters of individual patients. .

The researchers also plan to collect blood samples from a minimum of 1,000 patients recovered from COVID-19. Then, a variety of immune factors will be evaluated to study how they correlate with symptoms. The team hopes to be able to identify other potential parameters that influence the severity and clinical course of COVID-19. Investigators are currently looking for people who have confirmed cases of COVID-19 and subsequently recovered from the disease. They would also like to hear from people who, at some point in the past few years, developed infections subsequently confirmed to be caused by ‘common cold’ coronaviruses like 229E, C43, NL63, or HKU1.