Missing COVID-19 Antibodies Suggest Mysterious Immune Response

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Researchers at the Shanghai Public Health Center have made important discoveries about the immune response in patients who have recovered from mild COVID-19, which may help inform prevention and treatment methods, as well only to improve the effectiveness of community testing.

They found that many participants had high levels of neutralizing antibodies (NAbs) specific to the causative agent of the disease – severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, 30% did not have elevated levels of these antibodies, suggesting that other antibodies and immune factors contributed to their recovery.

Novel Coronavirus SARS-CoV-2: This scanning electron microscope image shows SARS-CoV-2 (round gold objects) emerging from the surface of cells grown in the laboratory. Credits: NIAID-RML

Novel Coronavirus SARS-CoV-2: This scanning electron microscope image shows SARS-CoV-2 (round gold objects) emerging from the surface of cells grown in the laboratory. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19. The virus shown was isolated from a patient in the United States. Credit: NIAID-RML

In addition to potentially providing useful information for antibody therapy and vaccine development, the results could help ensure that community tests are fast and sensitive enough to be effective and reliable.

About the pandemic

Since its epidemic in December 2019, the spread of COVID-19 has become a global threat to public health. To date, on April 13, the SARS-related coronavirus – SARS-CoV-2 – has caused 1,911,407 reported infections and 118,854 deaths.

Diagram of an influenza virus. Influenza A viruses are classified into subtypes based on the properties of their hemagglutinin (H) and neuraminidase (N) surface proteins. There are 18 different HA subtypes and 11 different NA subtypes. The subtypes are named by combining the numbers H and N - for example, A (H1N1), A (H3N2).
Diagram of an influenza virus. Influenza A viruses are classified into subtypes based on the properties of their hemagglutinin (H) and neuraminidase (N) surface proteins. There are 18 different HA subtypes and 11 different NA subtypes. The subtypes are named by combining the numbers H and N – for example, A (H1N1), A (H3N2).

Most people with the infection only had mild symptoms, but some 14% progressed to a more serious illness characterized by symptoms such as difficulty breathing and low oxygen saturation in the blood. In about 5% of cases, the condition has become critical, especially in people 60 years of age or older or those with existing health problems, and about 3.4% have died from organ or respiratory failure.

NAbs specific to the virus

The development of virus-specific NAb, either as a result of infection or immunization, is known to block and eliminate viral infections, and researchers expect (NAbs) against SARS-CoV -2 contribute to protection against disease and to the recovery of patients.

Passive antibody therapy using plasma or serum from recovered donors has already been shown to treat infections such as influenza, Ebola and SARS-CoV, and its effectiveness is correlated with levels of NAb or other antibodies donors. This therapy has been considered as a potential approach to prevent and treat COVID-19, but SARS-CoV-2 specific NAb have not yet been well studied in COVID-19 patients with clinical symptoms.

Now, Jinghe Huang and colleagues have used a sensitive, safe, and reproducible neutralization test to screen for SARS-CoV-2 specific ANB levels in plasma samples from 175 COVID-19 patients who had recovered from mild illness.

“Here, we sought to explore the clinical characteristics associated with the level of NAb in recovered patients, the results of which could provide useful information for the development of vaccines and passive antibody therapy for the prevention and treatment of SARS-CoV -2, ”wrote the team.

Although the document (available on MedRxiv) is currently in the pre-press stage and has not yet been peer reviewed, Eleanor Riley, professor of immunology and infectious diseases at the University of Edinburgh, says that ” it is a well written and methodologically sound study ”, and“ provides a very useful set of data. “

The main findings

The main conclusions were that most patients developed NAb specific to SARS-CoV-2 in the early stages of COVID-19 disease. NAb levels peaked 10 to 15 days after the onset of the disease, after which they remained stable.

University of East Anglia medical professor Paul Hunter said it “provides further evidence that if we are successful in deploying antibody tests, people would have to wait about two weeks after getting sick to get sick.” test”.

However, about 30% did not develop elevated levels of NAbs, but the duration of illness in these patients did not differ significantly from those who developed elevated levels.

“This is relevant to the current debate on antibody testing in the UK,” says Hunter. “If many people produce only low levels of antibodies to SARS-CoV-2, then any community test should have a high sensitivity. This helps to better understand why community antibody tests in the UK have not yet been authorized for use. “

In addition, for ten patients, the NAb were not detectable at all, indicating that other factors in the immune system such as cytokines or T cells may have contributed to recovery, suggest the researchers:

“If these patients were at high risk of rebound or reinfection, more studies should be explored,” they say.

Seniors may have had a stronger innate immune response

The team also reports that among those who developed NAb, the levels were significantly higher in elderly patients than in younger patients and correlated with markers of disease severity. Elderly patients had higher CRP blood levels and lower lymphocyte counts on admission to the center, suggesting a stronger innate immune response than younger patients.

“The question of whether the high level of NAb protects these patients from progression to severe and critical conditions deserves a full assessment,” the team wrote.

Results “should be deepened” for vaccine development

The authors state that to the best of their knowledge, their study is the first to report plasma NAb in patients who have recovered from COVID-19.

“The correlation of NAb titers with age, lymphocyte count and CRP blood levels suggested that the interaction between the virus and the host immune response in coronavirus infections should be further explored to developing an effective vaccine against the SARS-CoV-2 virus, ”he concludes the team.

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