ABSTRACT
Objectives The wide spectrum of clinical outcomes to SARSCoV-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, PCRand 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 interferonl-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.
ABSTRACT
P251 Figure 1Symptom score, virology, serology and nasal & serum cytokine data in the index case and their two PCR-positive household contacts since day of symptom onset at 4 timepoints across 28 days of follow up. A. Symptom score was calculated by allocating values for each self-reported symptom, weighted by self-reported severity, from a daily tracker;B. virology was measured by oropharyngeal swab RT-PCR. Samples below the detectable level were assigned value of 1;C-F. concentrations of 2 of the cytokines (IFNA1 and IP-10) measured in nasal lining fluid (C & E) and serum (D & F), measured by Meso Scale Discoveries U-plex assay. Grey dashed line indicates mean of healthy control values (C&E: n=4;D&F: n=5). Serum values for the fourth timepoint were not reported due to delayed sample processing.[Figure omitted. See PDF]ConclusionThese 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.ReferenceVabret N, Britton GJ, Gruber C, et al. Immunology of COVID-19: Current State of the Science. Immunity. 2020;52(6):910–41.