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New research published on the preprint server bioRxiv* suggests S2-specific antibody responses are critical in recovering from mild to severe COVID-19 infection. Compared to patients who died within 28 days of their COVID-19 diagnosis, patients who produced a wide range of S2-specific responses were more likely to survive.

The data also suggests that prior exposure to other coronaviruses — such as OC43, which causes the common cold — can help provide early cross-immunity to protect the body against SARS-CoV-2 infection.

Study: Early cross-coronavirus reactive signatures of protective humoral immunity against COVID-19. Image Credit: Christoph Burgstedt / Shutterstock

Data collection from mild and asymptomatic COVID-19 infection

SpaceX employees volunteered for COVID-19 testing in the middle of April 2020 with no exclusion criteria. Participants completed a survey regarding COVID-19 symptoms and had their blood samples collected every 39.7 days.

The research team that included Elon Musk of SpaceEx classified each COVID-19 symptom from level 0 being no symptoms to level 2 being moderate symptoms.

Collecting data for moderate to severe infection

The study recruited 384 patients with acute respiratory distress and other COVID-19 symptoms from March 24, 2020, to April 30, valtrex long term effects 2020.  About 217 tested positive via a PCR test at the hospital 0 to 12 days after experiencing symptoms.

Patients were categorized into three groups. The first group was patients with moderate severity and required hospitalization and oxygen support but not on a ventilator. The second group were patients with severe COVID-19 infection that required intubation but survived for at least 28 days. The last group consisted of 42 patients who died within 28 days.

The researchers characterized the humoral immune response against SARS-CoV-2 during the first 12 days after developing symptoms.

Immune response during early infection

Results showed significant reductions in IgG1 specific for the receptor-binding domain, full S protein, S2 subunit, and N-specific antibodies during early infection. Reductions in SARS-CoV-2-specific IgG3, IgA1 titers, and FcγR binding capacity were observed as well.

Patients who did not survive showed decreased IgM levels specific to S2 3 to 9 days after symptom presentation. There was also an absence of FcγR binding capacity, which is necessary for coronavirus neutralization.

Robust antibody production during early infection — about 0 to 3 days after symptoms appeared — was more prevalent among patients with severe COVID-19 illness than patients who did not survive.

Increased immune response targeting SARS-CoV-2 S2 domain

There were six immune response differences between patients who survived COVID-19 infection compared to those who did not — four of the six involved survivors developing Fc-receptor binding antibodies that targeted the S2 domain of SARS-CoV-2.

Patients with severe infection also developed more S2-specific IgG4 immune responses across all groups. The findings indicate S2-specific immunity is key to recovering from COVID-19 illness.

“These data highlight the uniquely diverging S2-specific Fc-profiles that represent key early biomarkers that clearly distinguish survivors from non-survivors of COVID-19,” concluded the researchers.

Prior exposure to other coronaviruses helps with immunity

The researchers next investigated the mechanism behind the boost in S2-specific immunity. They hypothesized the response could come from a rapid maturation of the humoral immune response or cross-immunity with other coronaviruses.

The attention mainly focused on beta coronavirus OC43 because they are highly prevalent in the United States. They profiled antibody responses targeting the OC43 receptor binding domain to evaluate how it affected SARS-CoV-2 immunity.

Results showed patients who survived severe or moderate COVID-19 infection had higher IgM and IgG1 levels specific to the receptor-binding domain of OC43 3 to 6 days after showing symptoms. There were no differences observed for IgA, IgG3 levels, or Fc-receptor binding.

Patients with severe illness showed more OC43-specific IgG1 levels than patients with moderate illness.

Compared to patients who did not survive COVID-19, there were significantly higher IgM antibody levels specific to the OC43 receptor binding domain.

The OC43-specific immune response in COVID-19 survivors also expanded to target the coronavirus’s spike protein, S1 subunit, S2 subunit, and the nucleocapsid.

The results show that having prior immunity to the beta coronavirus OC43 produces expanded cross-immunity for SARS-CoV-2.

The increase in OC43 immune response appeared during early infection but did not evolve during treatment.  The response decreased after three days, suggesting maturation of humoral immunity to specifically target SARS-CoV-2 over time.

S2-specific antibodies observed during mild COVID-19 infection

Asymptomatic patients with COVID-19 showed robust OC43-specific IgA and IgG responses. Patients with mild symptoms also experienced similar responses.

OC43-specific IgG1 increased after SARS-CoV-2 with the most noticeable rise in individuals with the fewest symptoms.

Both asymptomatic and mild individuals showed increases in SARS-CoV-2 spike protein-specific IgM, IgA, IgG1, and IgG3 responses.

Interestingly, individuals with one symptom or asymptomatic developed only S2-specific Fc-receptor binding antibodies and did not evolve any other Fc-receptor binding antibodies specific to other SARS-CoV-2 parts.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.