Does HHV-6B reactivate in COVID-19 patients?

So far only one case report has documented HHV-6B reactivation in COVID-19, but the rise in Kawasaki-like symptoms and pityriasis rosea has at least one dermatology group suspicious of HHV-6/7 reactivation.

Some physicians, who are working on the frontlines of the pandemic and are familiar with HHV-6 pathology, have noticed consistencies between some COVID-19 presentations and HHV-6B reactivation. Dr. Vincent Descamps, a dermatologist from the Bichat Hospital in Paris, France is currently treating COVID-19 patients. Descamps says that the cytokine storm and hemophagocytic syndrome seen in a few of their COVID-19 patients is similar to what is seen in DRESS/DIHS patients. He also reported that some patients have developed Pityriasis rosea, a rash associated with HHV-6 infection, and one patient had reactivation of Epstein-Barr virus.

The CD4+ T cells that are present in COVID-19 patients have significantly increased expression of the HHV-6B receptor, CD134 (OX40) (Zhou 2020). Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), a condition in which HHV-6 reactivation is common, is also associated with increased expression of CD134 on CD4+ T cells (Miyagawa 2016). Furthermore, high levels of the inflammatory cytokine IL-6 have been associated with serious HHV-6B reactivation, and again a similar increase in IL-6 is characteristic of COVID-19 patients. There have also been a few reports of a Kawasaki-like condition appearing in children with COVID-19, referred to as Pediatric Multisystem Inflammatory Syndrome (PMIS). Some characteristics of PMIS resemble the inflammatory conditions that often result in an increased risk of HHV-6 reactivation. All these similarities may be purely coincidental and a product of systemic infection by the coronavirus, but they beg the question of whether HHV-6 may play a role in COVID-19 pathology.

A publication from Necmettin Erbakan University in Turkey observed a significant increase in cases of Pityriasis rosea and Kawasaki’s disease and believe that this is related to the COVID-19 pandemic (Dursun 2020). The investigators retrospectively compared patient data from 1 April to 15 May 2019 to the patient data from the same period in 2020. In the 2019 period 0.8% and 0.03% of patients who were treated at the dermatology outpatient clinic were diagnosed with Pityriasis rosea and Kawasaki’s disease respectively. In 2020, during the pandemic, the rates of both conditions increased to 3.9% and 0.3% (p = 0.000 and p = 0.009 respectively).

So far there is only one documented case of HHV-6B reactivation Xi’an Jiaotong University, Xi’an, China. The patient described in this report is a 70-year-old male from Xi’an, China who presented with an ocular COVID-19 as well as persistent HHV-6B and HSV1 infection (Hu 2020).

Patients with severe cases of COVID-19 appear to have lower CD4+ and CD8+ T cell counts than other cohorts (Diao 2020; Qin 2020). The mechanisms behind this correlation are unknown, however T-cell depletion is also a characteristic of HHV-6 infection (Phan 2018).