P251 The induction of early, dynamic airway mucosal and systemic immune responses following recent SARS-CoV-2 household exposure

Journal article

Objectives

The wide spectrum of clinical outcomes to SARS-CoV-2 exposure suggests that early immune responses play a pivotal role.¹ We aim to describe early, longitudinal, local (nasal mucosal lining fluid) and systemic (peripheral blood) cytokine and cellular immune responses to SARS-CoV-2 in a symptomatic index case and their household contacts with detailed clinical and virological phenotyping. We hypothesise that immune responses at symptom onset would correlate with outcomes.

Methods

Participants from the London area are referred to INSTINCT study by general practitioners as suspected, or Public Health England as laboratory-confirmed, cases (ethical review details: IRAS 282820, approved 24.04.2020). Households are visited the day after identification and again on days 7, 15 and 28. Clinical and exposure questionnaires, samples of environment (surface swabs and air); oropharynx (swabs); nasal mucosa (synthetic absorptive matrix) and blood, and daily symptom diaries are collected. Samples are analysed by PCR, serology, 20-plex cytokine assay and flow cytometry in institutional laboratories.

Results

The index case was the first SARS-CoV-2 PCR-positive recruit of INSTINCT, confirmed on oropharyngeal swab 5 days after symptom onset. Contacts 1 and 2, the spouse and daughter, became symptomatic 2 days after the index case and were confirmed PCR-positive 3 days after symptom onset. The three PCR-positive individuals seroconverted during follow-up. Contact 3, the son, remained asymptomatic, PCR- and serology-negative throughout (figure 1a-b). None required hospitalisation. Swabs of the kettle and fridge handles were positive for virus, while other household surfaces and air samples were negative. Induction, peak and decline of interferon-λ-1 and IP-10 levels were captured in nasal mucosa, with lower serum levels (figures 1c-f).

Conclusion

These data demonstrate the ability of the INSTINCT household contact study to capture early immune responses in mild SARS-CoV-2 infection, not captured by COVID-19 hospital cohort studies. Early nasal mucosal cytokine responses to SARS-CoV-2 infection are not reflected in serum. The correlations observed provide cogent hypotheses that will be tested in the larger INSTINCT cohort, with implications for COVID-19 risk stratification, therapeutics, prophylaxis and vaccinology.

Reference

Vabret N, Britton GJ, Gruber C, et al. Immunology of COVID-19: Current State of the Science. Immunity. 2020;52(6):910–41.

Authors: Pillay, T; Kondratiuk, A; Davies, M; Narean, J; Tejpal, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BMJ Publishing Group
• Journal: Thorax
• Volume: 76
• Issue: Suppl 1
• Pages: A225-A226
• Publication date: 2021-01-21
• DOI: 10.1136/thorax-2020-btsabstracts.395
• EISSN: 1468-3296
• ISSN: 0040-6376
• Language: English
• Keywords: Asymptomatic; Medicine; Immune system; Internal medicine; Antibody; Immunology; Serology