SARS-Cov2 infection and DH:
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) patients have also begun to display DH. It is difficult to determine whether DH occurs more frequently following SARS-CoV-2 infections by looking at case reports/series alone. The latter, however, suggests that the clinical presentation of DH in SARS‑CoV‑2 patients is more extensive/severe [22, 40, 41]. Strikingly, according to the observations of others [42, 43] and ourselves, most of these DHRs were observed during the first wave of infections in 2020, and mostly in patients with a severe disease course. These DHs were characterized by an extensive cutaneous involvement, prominent eosinophilia, a slow clinical resolution, and, in DRESS patients, a lack of responsiveness to high-dose systemic corticosteroids.
Although it is tempting to hypothesize that SARS-CoV-2 itself could act as a warning signal and impact DH, our experimental findings suggest an indirect rather than direct effect in promoting DH via triggering cytokine storm. This, in turn, leads to the hyperactivation and enhanced expression of co-stimulatory molecules on APCs/monocytes [44] and primes a p-i T cell response to drugs. This is in line with the clinical observations that 1) these DHR seem to occur at the later stages of SARS-CoV-2 infections when the virus is barely still detected in the blood, and 2) that only patients with severe SARS-CoV-2 infections are affected.