Abstract
Olfactory and taste disorders (OTD) are commonly found as presenting symptoms of SARS-CoV-2 infection in patients with clinically mild COVID-19. Virus-specific T cells are thought to play an important role in the clearance of SARS-CoV-2; therefore the study of T cell specific immune responses in patients with mild symptoms may help to understand their possible role in protection from severe disease. We evaluated SARS-CoV-2-specific T cell responses to four different peptide megapools covering all SARS-CoV-2 proteins during the acute phase of the disease in 33 individuals with mild or no other symptom beside OTD and in 22 age-matched patients with severe infection. A control group of 15 outpatients with OTD and consistently negative nasopharyngeal SARS-CoV-2 RNA swabs and virus-specific IgG serology was included in the study. Increased frequencies of virus-specific CD4+ and CD8+ T cells were found in SARS-CoV-2 positive patients with OTD compared with those with severe COVID-19 and with SARS-CoV-2 negative OTD individuals. Moreover, enhanced CD4+ and CD8+ T-cell activation induced by SARS-CoV-2 peptides was associated with higher interferon (IFN)γ production. Increased frequencies of Spike (S1/S2)-specific CD4+ T cells showing enhanced IFNγ secretion and granzyme B content were associated with serum spike-specific IgG in the OTD group. In conclusion, patients with SARS-CoV-2 induced OTD develop highly functional virus-specific CD4+ and CD8+ T cells during the symptomatic phase of the disease, suggesting that robust and coordinated T-cell responses provide protection against extension of COVID-19 to the lower respiratory tract.
Highlights
The spectrum of clinical manifestations of SARS-CoV-2 infection typically spans from cold-like symptoms, cough and fever to severe interstitial pneumonia associated with shortness of breath and respiratory failure requiring assisted ventilation [1, 2]
Anosmia and dysgeusia have been described as the presenting symptom in more than 85% of patients with a mild form of COVID-19 [15, 16], while they are less prevalent in the severe forms of the disease, as indicated by studies reporting a lower rate of Olfactory and taste disorders (OTD) in hospitalized patients (5-35%) [17,18,19,20,21]
Using a cut-off threshold based on the median values obtained after stimulation with the vehicle control, the proportions of subjects above the threshold after stimulation with MP_R and MP_S was higher in the OTD-CoV-2pos group than in severe COVID-19 patients or OTD-CoV-2neg individuals (Figures 1D, E)
Summary
The spectrum of clinical manifestations of SARS-CoV-2 infection typically spans from cold-like symptoms, cough and fever to severe interstitial pneumonia associated with shortness of breath and respiratory failure requiring assisted ventilation [1, 2]. The pathogenesis of anosmia is thought to be related to the high expression of angiotensin-converting enzyme (ACE)-2 receptor, which binds SARS-CoV-2, on the sustentacular cells of the olfactory neuroepithelium, which has been shown to be expressed 200-700 fold more than on nasal or tracheal epithelia [22]. In light of this evidence, it has been surmised that, in patients with a stronger upper airway mucosal immunity, SARS-CoV-2 replication may induce a local inflammatory reaction which leads to ear nose and throat (ENT) symptoms and to the generation of an immune response protecting against the development of severe respiratory complications. Patients with weaker local immunity are thought to more likely develop severe disease [23]
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