Co-infections and Reactivation of some Herpesviruses (HHV) and Measles Virus (MeV) in Egyptian Cancer Patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Abstract

Abstract Background Coinfections and reactivation of persistent or latent viral infections such as herpesviruses (HHV) and/or measles virus (MeV) have been reported among COVID-19 patients. However, there is limited information regarding cancer patients who experienced severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The primary purpose of this study was to investigate the interplay between SARS-CoV-2, HHV and MeV in cancer patients, aiming to provide insights into the pathophysiology of these infections and to enhance the patients’ health outcomes. Methods A prospective observational study was conducted on 4 groups (n = 147): newly diagnosed cancer patients infected with SARS-CoV-2 (n = 37), newly diagnosed cancer patients non-infected with SARS-CoV-2 (n = 13), apparently normal individuals infected with SARS-CoV-2 (n = 82) and finally a normal control group (n = 15). All samples were tested for SARS-CoV-2 infection using the real-rime quantitative reverse transcription polymerase chain reaction (qRT-PCR). Antibody responses were analyzed using indirect enzyme-linked immunosorbent assay (ELISA), and antibody levels were compared between patients and controls. Potential re-activation was investigated using fourfold (i.e. 400%) rise model criterion. Results In all positive cases of SARS-CoV-2, recent infections or re-infection of herpes simplex viruses 1 and 2 (HSV1/2 or HHV1-2) were found to be significantly increased approximately three-fold higher in COVID-19 patients (p = 0.007) identified via pooled HSV1/2 IgM levels in plasma. Furthermore, reactivation of HSV1/2 was 29.7% in cancer/COVID-19 patients (n = 37) versus 0.0% of normal/COVID-19 group (n = 22) (p = 0.008). Likewise, Epstein-Barr Nuclear Antigen-1 (EBNA-1) IgG levels showed a ≥ fourfold increase in 20% (p = 0.034) of cancer patients (n = 50) versus 4.9% of controls (n = 41) for reactivation of Epstein-Barr virus (EBV or HHV-4). Obviously, MeV IgG levels increased up to 78.0% in cancer patients (n = 50) versus 17.5% in non-cancerous group (n = 40, p < 0.001). Reactivation of MeV in cancer and COVID-19 patients was 43.2% versus 30.8% cancer non-COVID-19 group, 3.3% normal COVID-19, and 0.0% in healthy volunteers (p < 0.001). Conclusion Cancer patients infected with SARS-CoV-2 were at increased risk of HHV and MeV co-infection and reactivation.

Keywords

• Cancer
• COVID-19
• SARS-CoV-2
• Measles Virus (MeV)
• Human Herpesviruses (HHVs)
• Viral reactivation