Levels and types of SARS-CoV-2 antibody vary depending on the severity of the disease, a study found

Researchers have measured antibody levels and types in patients with hospital-acquired coronavirus infection 2019 (COVID-19) with various inflammatory bowel diseases. Their findings suggest that gut immune pathways may play a role in reducing inflammation and virus overgrowth.

COVID-19, the disease caused by acute respiratory coronavirus 2 (SARS-CoV-2) syndrome, affects humans differently. Some patients are asymptomatic, but in others, the disease can be fatal. However, the reasons for this variability in symptoms are not yet fully understood. Studies suggest that a person’s immune response to the virus may be important in determining how the disease progresses.

Infection of SARS-CoV-2 causes the immune system to produce neutral antibodies against the spike protein of the virus or the nucleocapsid protein. Higher levels of antibodies have been observed in patients with very severe symptoms of disease, suggesting that antibody response affects not only virus clearance but also immunopathology. In addition to their neutral properties, antibodies may have properties that can lead to increased inflammation or increased antibody-dependent infection.

Of the four types of IgG antibodies, IgG1 and IgG3 are considered pro-inflammatory because they can inhibit and deliver powerful immune signals. The character of the different types of antibodies can provide information about the immune response.

Types of antibody vary with depth of disease

To do so, researchers identified serum antibodies to the spike protein and the nucleocapsid protein obtained from hospitalized COVID-19 patients with moderate to severe infection. They reported their findings in a paper published on the medRxiv* preprint server.

The authors collected serum samples from 38 patients between March and May 2020, within 44 days of the onset of the symptom. They identified the types of antibodies by isotyping for IgG, IgA, and IgM and subtyping into IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2 using ELISA.

They found higher amounts of antibody classes and receptor binding domain (RBD) subclasses in COVID-19 patients than pre-pandemic control samples. Most patients had IgG1 and IgG3 subclasses. The RBD-specific IgA response included IgA1 and IgA2 subclasses. In the nucleocapsid-specific antibodies, they detected IgG1 and IgG3 in the majority of patients.

Next, the authors assigned a group of patients based on antibody titers to RBD and nucleocapsid proteins, along with patient demographic data. They found that RBD-specific IgA antibodies were combined with RBD-specific non-inflammatory IgG2 and IgG4 antibodies and isolated nucleocapsid protein-specific antibodies collected by RgD-specific IgG1, IgG3, and IgM.

They found four groups of COVID-19 patients when grouped according to antibody levels. Patients in the early stages of the disease had RgD-specific IgA and IgD and IgG3-specific IgG1. The next group of patients with moderate infection showed particularly low IgG1 and IgG3 antibodies with or without RBD. Patients with more severe infection had maintained RBD-specific IgG responses. Patients with severe disease received an IgG response of both RBD and nucleocapsid proteins in combination with IgA antibodies.

Capable of gut immune system

Further analysis of the results showed that higher levels of RBD-specific IgG1, and significantly lower IgG3 levels, are associated with a higher disease rate. The authors used machine learning modeling to find the minimum number of variables that could differentiate patients based on the severity of disease. They found RgD-specific IgG levels to determine the severity of the disease. IgG2 and IgG4 subclasses were not associated with disease rate. They also found that the IgA response, seen mainly in patients with gastrointestinal symptoms, was associated with positive clinical outcomes.

Previous studies have reported that SARS-CoV-2 neutral antibody levels are higher in hospitalized patients. The higher IgG1 and IgG3 levels seen in severe disease may be due to the fact that they can exacerbate inflammation at advanced disease levels. The authors found that these antibodies also bind to serum LDH and ferritin, which are biomarkers for inflammation. Antibodies to nucleocapsid proteins do not bind to disease depth, but the reasons for this are not yet clear.

In addition to the IgG antibodies, the authors also found IgA and IgM antibodies specific to RBD and nucleocapsid proteins. However, IgA1 and IgM were not associated with disease or inflammation biomarkers. IgA1 is found in both the intestine and the respiratory tract, and IgA2 is found mainly in the abdomen. The observations of IgA2 in some COVID-19 patients suggest a gut immune response.

Recent observations indicate that gastrointestinal symptoms of COVID-19 have favorable clinical results and increased survival. The authors also found a negative correlation between RBD-specific IgA2 titers and hospital days. These findings suggest that gut immunity may reduce the severity of COVID-19 infection and improve recovery. Because there is a large interaction between the gut and respiratory mucus membrane, gut immune responses may reduce lung inflammation in COVID-19 patients. However, this idea needs to be further proven.

* Important message

medRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.