"Nature": Significant progress has been made in research on the new crown!

good news! Really good news.

Today, a research team led by Ali H.
Ellebedy of the University of Washington School of Medicine published a paper in the top journal “Nature”, saying: They found new coronavirus-specific long-lived bone marrow plasma cells (BMPCs) in the bone marrow of patients with mild new coronary pneumonia.
, An effector B cell) [1].

Such cells will survive for life and continue to release antibodies.

This finding shows that, at least for people who have recovered from mild coronavirus, the new coronavirus induces a strong antigen-specific, long-lasting humoral immune response in their bodies.

In addition, it is worth mentioning that this is the first time it has been confirmed that the virus can induce antigen-specific BMPCs after infecting humans.

According to previous research, we already know that the re-infection of seasonal coronavirus generally occurs 6-12 months after the previous infection [2].

This indicates that the human body's protective immunity to these viruses may be short-lived [2].

At the beginning, scientists discovered phenomena in blood samples of survivors of new coronary pneumonia, which made us think that the new coronavirus may have similar characteristics.

For example, some studies have found that serum antibodies against the new coronavirus rapidly decay in the first few months after infection [3, 4].

This has aroused the concern of researchers, because it may mean that long-lived BMPCs are not produced in the recovered body, after all, long-lived BMPCs are the persistence and basic source of protective antibodies [5-7].

Some researchers even believe that the new coronavirus infection may not cause the response of the functional germinal center (mainly composed of B cells), and this will seriously affect the production of long-lived BMPCs [8].

The new coronavirus (source: NIAID-RML) However, the good news is that when researchers analyzed samples collected 4 to 6 months after infection, they found that the antibody titer of the new coronavirus decreased slowly [9, 10].

Moreover, studies have found that the risk of re-infection in patients who have recovered from new coronary pneumonia is significantly reduced [11, 12].

There are various signs that the new crown survivors should have long-term immunity to the new crown pneumonia.

What is the truth? Ellebedy realized that the key to the problem lies in the bone marrow in order to find out whether there is durable antibody immunity in the body of patients who have recovered from coronary pneumonia.

Have to study bone marrow, friends.

Compared with blood samples, obtaining bone marrow samples is much more difficult.

New crown virus (Source: NIAID-RML) In this study by Ellebedy, they recruited 77 patients who have recovered from mild new crown pneumonia, 49% of whom were women and 51% were men, aged between 21 and 69.
Between, the median age is 49 years old.

Six of them have been hospitalized.

All patients started about one month after the initial infection and provided blood samples every three months.

The most critical bone marrow sample was also obtained by the Ellebedy team.
With the help of Iskra Pusic[13], they collected bone marrow from 18 survivors who had been diagnosed with the new coronavirus for seven or eight months; 4 months later, some of them Five people contributed another bone marrow.

As a control, they also collected bone marrow from 11 people who had never been infected with new coronary pneumonia.

Blood sample and bone marrow sampling time Based on the above experimental materials, Ellebedy and his colleagues found that the antibody level in the blood of survivors of the new crown declined rapidly in the first few months after infection, and then stabilized, some people even 11 months after infection Some antibodies can also be detected.

This is basically consistent with the previous research data.

The trend of blood sample antibody changes over time is next to study an important question: whether there are new coronavirus-specific long-lived BMPCs in the bone marrow of COVID-19 patients.

To this end, they enriched BMPCs from bone marrow samples and analyzed the frequency of influenza virus vaccine, tetanus/diphtheria vaccine and new coronavirus S protein specific IgG and IgA in 2019/2020.

They found that the frequency of influenza and tetanus/diphtheria vaccine-specific BMPCs was comparable between the control group and the recovered.

Analysis of influenza and tetanus/diphtheria vaccines, new coronavirus S protein-specific BMPCs, and then look at new coronavirus S protein specific cells.

Of the 19 bone marrow samples from patients who recovered from COVID-19, 15 contained antibody-producing cells specific to the S protein of COVID-19, and no such cells were detected in 11 control participants.

It is worth mentioning that at the time of bone marrow sampling, no S protein-specific antibody secreting cells were detected in the blood of all recovered patients.

This indicates that the BMPCs detected by the researchers are bone marrow resident cells, rather than contamination from circulating plasma cells.

Comparison of influenza and tetanus/diphtheria vaccines and new coronavirus S protein-specific BMPCs As for the second bone marrow sample collected 4 months later by 5 recovered patients, the researchers found that the frequency of anti-S IgG BMPCs was stable, while anti-S IgA The frequency of BMPCs was stable in 4 out of 5 people, and one of them dropped below the detection threshold.

Comparison of new coronavirus S protein-specific BMPCs at different times.
Ellebedy has his own understanding of his research results.
He believes that [13]: "Patients with mild new coronary pneumonia will clear the virus from the body two to three weeks after infection.
After 7 or 11 months of infection, there will be no active virus-driven immune response.

” In addition, Ellebedy also believes [13] that these new coronavirus-specific BMPCs are in a static state, not dividing, but staying quietly in the bone marrow.
, Secrete antibodies silently, and they will continue to do so indefinitely.

For those with asymptomatic infection, Ellebedy speculates that they may also have long-term immunity [13].

However, whether there is long-term immunity for those severely infected people still needs further research.

The first author Jackson Turner believes that the excessive inflammatory response of severely infected patients may lead to a defect in the immune response, so it is not certain whether there are new coronavirus-specific long-lived BMPCs in such patients [13].

As for whether the new crown vaccine will induce the production of long-lived BMPCs, Ellebedy and colleagues said they are studying [13].

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