The clinical manifestations of SARS-CoV-2 infection vary from one individual to the next, and much remains unknown about the mechanisms underpinning this variability. Since the nasal mucosa is one of the first entry points of the virus, scientists from the Institut Pasteur and Inserm, in collaboration with Cochin AP-HP Hospital, analyzed in parallel the immune responses in the nasal mucosa and in the blood of individuals infected by SARS-CoV-2. The scientists demonstrated that in these COVID-19 patients, the immune responses in the mucosa and the blood were differentially and independently regulated. They also observed perturbations in the nasal microbiota, and presence of opportunistic pathogenic bacteria that may cause secondary bacterial infections. These findings were published in Nature Immunology on September 1, 2021.
The response to SARS-CoV-2 infection varies from one individual to the next, ranging from mild symptoms to severe pneumonia. Much remains unknown about the immunological mechanisms
underlying this variability. Since the nasal mucosa is usually one of the first entry points of the virus, scientists from the Institut Pasteur and Inserm, in collaboration with Cochin AP-HP Hospital, analyzed the immune responses in the nasal mucosa (local responses) and in the blood (systemic responses) of patients who had contracted COVID-19.
The scientists made an in-depth analysis of the immune response: studying antibodies directed against SARS-CoV-2, cytokines and bacterial populations (the nasal microbiota) in nasopharyngeal swabs and blood samples taken from patients infected with SARS-CoV-2. The samples were taken from a patient cohort at Cochin Hospital 8 to 12 days after the onset of the first symptoms.
The results show that the immune response associated with the production and neutralizing capacity of SARS-CoV-2 antibodies was not the same in the nasal mucosa and in the blood. "Surprisingly, patients with nasal antibodies did not always have antibodies in the blood, and vice versa," says Darragh Duffy, Head of the Translational Immunology laboratory at the Institut Pasteur and joint last author of the study. Local immune responses (in the mucosa) and systemic immune responses (in the blood) to the virus may therefore be regulated independently.
The authors of the study also looked into cytokine production. They observed that the production of cytokines was also different in the nasal mucosa and in the blood. "All these results suggest that both cytokine responses and SARS-CoV-2 antibodies are regulated in a tissue-dependent way," explains James Di Santo, Head of the Innate Immunity Unit/Inserm U1223 at the Institut Pasteur and joint last author of the study.
The scientists also identified significant changes in the microbial species that populate the nasal mucosa in COVID-19 patients. In the same patient cohort, they observed an increase in potentially pathogenic microorganisms that are often involved in secondary respiratory infections. "SARS-CoV-2 infection could disrupt the nasal microbiota, indicating that there may be a link between the nasal microbiota and protective antiviral pathways," continues James Di Santo.
"Our results shed new light on local immune responses in the nasal mucosa, one of the first sites of infection with the SARS-CoV-2 virus," concludes Darragh Duffy. The scientists' observations suggest that modulating local immune defenses using techniques such as nasal vaccination could represent a preventive strategy against COVID-19.
Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection, Nature Immunology, Septembre 1st, 2021
Nikaïa Smith (1,16), Pedro Goncalves (2,16), Bruno Charbit ( 3), Ludivine Grzelak (4,5), Maxime Beretta (6), Cyril Planchais (6), Timothée Bruel (4), Vincent Rouilly (7), Vincent Bondet (1), Jérôme Hadjadj (8,9), Nader Yatim (1,8), Helene Pere (10), Sarah H. Merkling (11), Amine Ghozlane (12), Solen Kernéis (13,14,15), Frederic Rieux-Laucat (9), Benjamin Terrier (8), Olivier Schwartz ( 4), Hugo Mouquet (6), Darragh Duffy ( 1,17,*), and James P. Di Santo (2,17,*).
1 Translational Immunology Lab, Institut Pasteur, Paris, France.
2 Innate Immunity Unit, Institut Pasteur, INSERM U1223, Paris, France.
3 Cytometry and Biomarkers UTechS, Institut Pasteur, Paris, France.
4 Virus and Immunity Unit, Institut Pasteur, Paris, France.
5 Sorbonne Paris Cité, Université de Paris, Paris, France.
6 Humoral Immunology Laboratory, Institut Pasteur, INSERM U1222, Paris, France.
7 DATACTIX, Paris, France. 8Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Assistance Publique Hôpitaux de Paris-Centre (APHP-CUP), Université de Paris, Paris, France.
9 Imagine Institute, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Université de Paris, Paris, France.
10 Unité de Génomique Fonctionnelle des Tumeurs Solides, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.
11 Insect-Virus Interactions Unit, Institut Pasteur, CNRS UMR2000, Paris, France.
12 Hub de Bioinformatique et Biostatistique, Institut Pasteur, Paris, France.
13 Equipe Mobile d’Infectiologie, Hôpital Cochin, AP-HP, APHP-CUP, Paris, France.
14 Université de Paris, INSERM, IAME, Paris, France.
15 Epidemiology and Antimicrobial Resistance Modeling Laboratory, Institut Pasteur, Paris, France.
16 These authors contributed equally: Nikaïa Smith, Pedro Goncalves.
17 These authors jointly supervised this work: Darragh Duffy, James P. Di Santo.