The coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), impacts patients in various ways. While most people develop only mild to moderate symptoms, some patients experience severe and potentially fatal symptoms.
COVID-19 presents with a wide range of clinical manifestations characterized by misdirected and exaggerated innate immune responses. The role of autoantibodies in disease progression is unknown, but these activations have been well documented for patients with severe disease.
A cytokine storm has been cited as a significant contributor to severe symptoms. This is because of the immune system going haywire and causing massive damage to vital organs. Much remains unknown about the path the virus takes in severe cases, but past evidence shows a hyperactive immune response is tied to COVID-19 death.
Researchers at Yale University showed that the development of antibodies to the SARS-CoV-2 infection might go berserk and rogue, causing severe cases of COVID-19. These antibodies target and react with the body's tissues and organs, similar to those that cause autoimmune diseases, including rheumatoid arthritis and lupus.
The study, published in the journal Nature, sheds light on the disease mechanism of COVID-19 and how the virus causes a faulty immune system.
SARS-CoV-2 and autoantibodies (AAb)
Humoral immunity plays a pivotal role in COVID-19. Though neutralizing antibodies protect against SARS-CoV-2 infection, growing evidence shows that dysregulated humoral immunity also contributes to the severity of COVID-19 in some people. These include elderly people, those with immune system problems, and those suffering from heart disease, diabetes, kidney failure, hypertension, or respiratory illness.
Past studies have identified isolated autoantibody reactivities in COVID-19 patients, particularly neutralizing antibodies against the interferon type 1 (IFN-1), which appear to contribute to COVID-19 severity directly.
Despite the fact that autoantibody responses have been described, it is unclear how reactivated antibodies affect patients. These include exoproteome-targeting autoantibodies that cause functional effects, including the targeted killing of cells.
In the current study, the researchers aimed to identify functional autoantibody responses in COVID-19 patients. They screened for autoantibody reactivities against the human exoproteome.
The researchers utilized a high-throughput autoantibody discovery technique known as Rapid Extracellular Antigen Profiling (REAP) to arrive at the study findings. The team screened a group of 194 SARS-CoV-2-infected patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins.
The researchers found that COVID-19 patients manifest marked elevation in autoantibody reactivities compared to uninfected controls. Additionally, they exhibited an abnormal prevalence of autoantibodies to immunomodulatory proteins, such as chemokines, cytokines, and cell surface proteins.
This shows the link between autoantibodies produced by the immune system and cytokines, which have been tagged as culprits in severe cases of cytokine storm among COVID-19 patients.
Further, the team revealed that the autoantibodies alter immune function and impair viral control by inhibiting immunoreceptor signaling. The autoantibodies perform this by altering peripheral immune cell composition. The murine surrogates of these autoantibodies aggravate disease severity in laboratory mice with SARS-CoV-2 infection.
When the team examined the autoantibodies against tissue-associated antigens, they found the link between specific clinical characteristics and disease severity.
Overall, the team noted the role of exoproteome-directed autoantibodies in the COVID-19 disease process with various effects on immune functionality and clinical outcomes.
"Our findings reinforce the importance of getting vaccinated. The fact that even mild infections are associated with autoantibody production underscores the potential for long-term health consequences of COVID-19," Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology at Yale, said.
There are more than 165 million infections from SARS-CoV-2 COVID-19 globally and over 3.43 million deaths since the start of the pandemic. The United States remains with the highest number of COVID-19 cases, reaching over 33 million, followed by India with over 26 million cases.