Background:
Reactivation of Herpes Human Viruses (HHV) has been described mostly in severe SARS-CoV-2 patients (pts) [1]. We aim to study HHV reactivation, HHV-mediated T-cell response and inflammatory milieu during SARS-CoV-2-mild infection.
Methods:
We enrolled pts with SARS-COV-2 infection at baseline (T0), days 7 (T7) and 30 (T30) and healthy donors (HD). We evaluated HHV-serology, HHV-DNA-plasma level and the IFN-γ production after whole blood stimulation with SARS-CoV-2-spike peptides, HHV peptides designed to elicit CD4/CD8 response for Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), HHV1/2, Epstein-Barr virus (EBV), and IL-2, IL-6, IL-8, TNF-, IFN-γ, CXCL-10 plasma levels.
Results:
We enrolled 19 HD and 53 COVID pts with WHO median score 2 (IQR 2-4). No differences in terms of age, sex, and SARS-CoV-2 vaccinations in the 2 groups were observed. All HD referred a previous SARS-CoV-2 infection. There were no clinical HHV reactivations. At T0, no difference in lymphocytes count (while CD3 and CD4 T cells differed both with a p<0.01), in HHV-seroprevalences, HHV-antibodies level and HHV reactivation were reported between groups. Blood EBV-DNA was more commonly detected at T0-T7-T30, with no difference between groups. A higher CMV-T-cell response compared to that induced by the other HHV was constantly found in both pts (p<0.0001) and HD (p=0.003). However, the CMV-CD8 response of pts was significantly higher compared to HD at T30 (p=0.032), whereas the EBV-induced CD4 and CD8 response was lower compared to HD at T0 and T7 (T0 p=0.005; p=0.003; T7 p=0.008 p=0.003). As expected, at T7 the SARS-CoV-2 response of pts was higher compared to HD (p=0.026). In pts an increased EBV-CD8 response (T0/T7 p=0.005; T0/T30 p=0.0004) was reported. Pts showed the highest SARS-CoV-2-specific response at T7 compared to T0 (p=0.044). No difference in HD over time was found. Plasma IL-2, IL-6, IFN-γ and CXCL-10 were significantly higher at T0, T7 in pts compared to HD (for all p<0.007), while no difference at T30 was observed.
Conclusions:
Inflammatory milieu, HHV T-cells response are present during SARS-CoV-2 mild infection, despite not significant plasma HHV detection. In COVID pts we observed a consistently high CMV and a decreased EBV T-cell response, probably reflecting EBV viremia. Indeed, among HHV, the CMV response appears to be the driving force with a higher CD8-mediated proportion. The identification of subclinical HHV-reactivation during SARS-CoV-2 mild infection is worthy of further investigations.
