August 2020 is about to end, but COVID-19 has not stopped, especially the second wave of epidemics in France, Spain and other countries recently, which can be described as menacing. This situation is related to their treatment: natural infection → herd immunity.

In Spain, where the epidemic is serious, the positive rate of antibody testing is only 5%, which is far below the threshold of herd immunity; and the neutralizing antibodies in many severely ill patients cannot maintain the level required for subsequent immune infections for a long time.

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Why can’t the natural infection of COVID-19 keep patients immune for a long time?

In the recent “Cell”, the Harvard University research team released a new discovery: the “cytokine storm” secondary to the new crown pneumonia infection may affect the production of human memory B cells, making it difficult for patients to maintain exposure to the new coronavirus. Long-term immunity!

This study found that in the lymph nodes and spleen of patients with severe new coronary pneumonia, the germinal centre (germinal centre), a structure necessary for the production of memory B cells, is obviously missing, and it also lacks the one that can express the transcription factor BCL-6 to help the germinal centre form. Follicular helper T cells.

In critically ill patients with cytokine storms, this lack of germinal centres is the most obvious, so the patient’s humoral immune function in response to secondary infections will be significantly affected. Studies believe that tumour necrosis factor-α (TNF-α) and other cytokines, which are significantly increased after infection, are the main reason for this phenomenon.

In fact, as early as when SARS and MERS were two respiratory infectious diseases that were also caused by coronaviruses, studies pointed out that with the exception of a few patients, most of the patients who were naturally infected could not maintain a high level of specific antibodies in the body for a long time. , But the reason for this phenomenon has not been explained clearly.

Although studies have suggested that new coronaviruses and other coronaviruses that infect humans may cause lymphopenia, atrophy or even exhaustion of lymph nodes, similar situations have also occurred in infections with other viruses or pathogens. What is special about the coronavirus infection that causes the long-term humoral immunity to be unable to be established, and further analysis is needed.

In this study, the Harvard University team first compared the lymph nodes of the thoracic cavity of patients who died of new coronary pneumonia with the lymph nodes of people who died of other causes and found that patients with severe new coronary pneumonia died within 10 days of infection. He died 15 days later, and there was a significant lack of germinal centres in the lymph nodes.

Following the analysis of the spleen, the main immune organ, the research team also reached a similar conclusion-the B cells and T cells in the spleen of patients with severe new coronary pneumonia were significantly reduced, and BCL-6, which plays an important role in the formation of germinal centers, was positive. B cells and BCL-6 positive follicular helper T cells are lacking.

When analyzing the tonsils of patients with new coronary pneumonia, the research team discovered the reason that may lead to the decrease of lymph nodes and spleen germinal centres-there are a large amount of TNF-α around the tonsil follicles. Last year, a study showed that the cytokine storm after bacterial infection Among them, a large amount of TNF-α will inhibit the formation of germinal centres

Although further analysis shows that even without the help of germinal centres and follicular helper T cells, the human immune system can still produce a certain humoral immune response, but because the differentiation and maturation of B cells are affected, both immune strength and efficiency are obvious Weakened, it is difficult to maintain long-term humoral immunity.

Research author Shiv Pillai said, “Without a germinal center, there is no long-term immune memory of antigens”, which is why other coronaviruses may repeatedly infect the human body. But the research team also said that because the new crown vaccine generally does not cause a cytokine storm, the protective effect of the vaccine should not be affected by this discovery.

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