SARS-CoV-2 infection generates tissue-localized immunological memory in humans

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Adaptive immune responses to SARS-CoV-2 are well-studied in blood.
• Protective immunity relies heavily on tissue-level immune functions.
• Understanding tissue-resident memory is key for long-term protection.

Purpose of the Study:

• To investigate the presence and distribution of SARS-CoV-2 specific immune memory cells in various tissues.
• To determine the duration of immune memory in tissues up to six months post-infection.
• To explore the correlation between circulating and tissue-resident immune memory.

Main Methods:

• Analysis of immune cells (CD4+, CD8+ T cells, B cells) from organ donors (ages 10-74) up to 6 months post-SARS-CoV-2 infection.
• Examination of bone marrow, spleen, lung, and lymph nodes for SARS-CoV-2 specific immune cells.
• Identification of germinal centers and follicular helper T cells in lymphoid tissues.

Main Results:

• SARS-CoV-2 specific CD4+ T, CD8+ T, and B cell memory were detected in bone marrow, spleen, lung, and lymph nodes up to 6 months post-infection.
• Lungs and lung-associated lymph nodes showed the highest prevalence of SARS-CoV-2 specific memory T and B cells.
• Significant correlations were observed between circulating and tissue-resident memory cells across all examined sites.
• SARS-CoV-2 specific germinal centers and follicular helper T cells were identified in lung-associated lymph nodes and lungs.

Conclusions:

• Immune memory against SARS-CoV-2 is established and maintained in various tissues for at least six months.
• Lungs and associated lymph nodes are critical sites for SARS-CoV-2 specific cellular and humoral immune memory.
• Local tissue immune memory contributes to site-specific protection against future SARS-CoV-2 challenges.