Human herpesvirus‐6, ‐7, and Epstein‐Barr virus reactivation in pityriasis rosea during COVID‐19

Abstract

Cutaneous manifestations during coronavirus disease 2019 (COVID-19) include pityriasis rosea (PR) and PR-like eruptions.1-3 We describe a patient with PR demonstrating that concurrent viral reactivations may occur during COVID-19. A 16-year-old boy presented with a cutaneous eruption, fever (37.5°C), and systemic symptoms (headache, fatigue, arthralgias, myalgias, loss of appetite, inability to concentrate, and drowsiness). On examination, symmetrical oval erythematous papulosquamous lesions were observed over the trunk in the typical “Christmas tree” distribution. The eruption was preceded by a single scaly oval patch on the abdomen. Erythematous macules with petechiae were localized on the hard and soft palate (Figure 1). PR was diagnosed. Three weeks earlier, the patient's mother and father had COVID-19. Blood investigations revealed leukopenia (3.1 × 109/L) and lymphopenia (900 cells/109L, normal values [nv] > 1200 cells/109L) with reduced CD4+ T cells (450, nv: 500–1300 /μl) and CD8+ T cells (180, nv: 225–1180/μl). Routine investigations and chest X-rays were normal. Serology for cytomegalovirus, hepatitis A, B, and C viruses, human immunodeficiency virus, and parvovirus B19 was negative or indicative of past immunity. Treponema pallidum hemagglutination assay was negative. Serology for Epstein-Barr virus (EBV) revealed immunoglobulin M (IgM) against the viral capsid antigen (VCA; titers 1/160), anti-VCA immunoglobulin G (IgG; 1/320), antiearly antigen IgG (1/160), and anti-Epstein-Barr nuclear antigen IgG (1/80). Serology was positive for human herpesvirus-7 (HHV-7) and HHV-6, with IgG at 1/80 and 1/320, respectively. IgM titers attained 1/80 and 1/160, respectively. HHV-6 DNA (viral load: 420 viral genome equivalents/ml) was found in plasma by calibrated quantitative (CQ) RT-PCR,4 while HHV-7 DNA was undetectable. Plasma EBV-DNA (530 copies/ml) was detected by CQ RT-PCR. High-avidity EBV and HHV-6 IgG antibodies (avidity index value 61%; cut-off > 50%) were found in the serum demonstrating reactivation of latent infection. The nasopharyngeal swab test proved positive for SARS-CoV-2 by CQ RT-PCR assay. Systemic symptoms and cutaneous lesions cleared in 4 weeks. Six weeks later IgM antibodies against EBV and HHV-6 were persisting (titers of 1/80), lymphopenia recovered (1600 cells/109L) and HHV-6 and EBV DNA in plasma were undetectable. Two consecutive nasopharyngeal swabs were negative for SARS-CoV-2. Coinfections may attain up to 50% of COVID-19 nonsurviving patients. Copathogens include bacteria, fungi and viruses-like influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus.5 We demonstrated that in the setting of COVID-19 it is possible to find the reactivation of other viral infections as HHV-6, HHV-7, and EBV. Several PR and PR-like eruptions have been described during COVID-19.1 Regrettably, in none of them HHV-6/7 viral reactivations have been investigated, although their pathogenetic role in PR is well-known.4 Thus, the possible relationship between COVID-19 and HHVs remains unsettled. We suggest that SARS-CoV-2 may have played a transactivating role, triggering HHV-6, HHV-7 and EBV reactivation and, consequently, causing cutaneous PR manifestations.6 Lymphopenia may have favored this mechanism. On its turn, it has been demonstrated that HHV-6 can have reactivated EBV, independently.7, 8 Overall, SARS-CoV-2 may have triggered a chain viral reaction. Two cases in the literature may show similarities with ours. Lamentably, none of them have possible HHV-6 and HHV-7 viral reactivations been considered. Sanchez et al.9 found EBV reactivation in a patient with a skin eruption (suggesting an atypical PR) associated with COVID-19. Importantly, PCR for SARS-CoV-2 in a fresh skin biopsy specimen of the same patient proved negative. Furthermore, Gianotti et al.10 revealed ballooning and multinucleated keratinocytes in a patient with diffuse skin eruption and COVID-19. Such cytopathic effects might be due to HHV-6 and/or HHV-7 reactivation, but no specific virologic investigations in the patient's blood or skin were performed. Actually, the pathogenesis of COVID-19 could not be simply related to the effect of SARS-CoV-2 on the targeted tissues, but the damage of lung, kidney, and other organs could be the result of a systemic immune-mediated inflammatory environment, which includes the endothelium and tissues infected by the SARS-CoV-2.11 In this view, the multisystem inflammatory syndrome related to SARS-CoV-2 infection may cause multiple viral reactivations that, in turn, may contribute to the patient's systemic inflammation. Since it has been established that coinfections may influence morbidity and mortality in COVID-19 patients,5, 12 additional studies are warranted to establish whether concurrent viral reactivations during COVID-19 could influence disease outcomes. The authors declare that there are no conflict of interests.

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