Metagenomic Next-Generation Sequencing in the Diagnosis of HHV-1 Reactivation in a Critically Ill COVID-19 Patient: A Case Report

Background: Secondary infections pose tremendous challenges in Coronavirus disease 2019 (COVID-19) treatment and are associated with higher mortality rates. Clinicians face of the challenge of diagnosing viral infections because of low sensitivity of available laboratory tests. Case Presentation: A 66-year-old woman initially manifested fever and shortness of breath. She was diagnosed as critically ill with COVID-19 using quantitative reverse transcription PCR (RT-qPCR) and treated with antiviral therapy, ventilator and extracorporeal membrane oxygenation (ECMO). However, after the condition was relatively stabled for a few days, the patient deteriorated with fever, frequent cough, increased airway secretions, and increased exudative lesions in the lower right lung on chest X-rays, showing the possibility of a newly acquired infection, though sputum bacterial and fungal cultures and smears showed negative results. Using metagenomic next-generation sequencing (mNGS), we identified a reactivation of latent human herpes virus type 1 (HHV-1) in the respiratory tract, blood and gastrointestinal tract, resulting in a worsened clinical course in a critically ill COVID-19 patient on ECMO. Anti-HHV-1 therapy guided by these sequencing results effectively decreased HHV-1 levels, and improved the patient\u27s clinical condition. After 49 days on ECMO and 67 days on the ventilator, the 66-year-old patient recovered and was discharged. Conclusions: This case report demonstrates the potential value of mNGS for evidence-based treatment, and suggests that potential reactivation of latent viruses should be considered in critically ill COVID-19 patients

ALT level negatively associated with stress and anxiety.

<p>(A)Comparison of ALT between high and low perceived stress group; (B) Comparison of ALT between high and low state anxiety; (C) Comparison of ALT between high and low trait anxiety. <i>P</i> value was indicated.</p

Shift of the type-1/type-2 cytokine balance towards a type-2 cytokine response in high perceived stress patients.

<p>(A)Comparison of INF-γ between low and high perceived stress group; (B) Comparison of IL-10 between low and high perceived stress group; (C) Comparison of INF-γ:IL-10 ratio between low and high perceived stress group. <i>P</i> value was indicated.</p

Comparison of lymphocytes count and circulating cytokines between low and high perceived stress patients with hepatitis B.

<p>Comparison of lymphocytes count and circulating cytokines between low and high perceived stress patients with hepatitis B.</p

Sociodemographic, disease-specific characteristics comparison between high and low perceived stress and anxiety patients with chronic hepatitis B.

a<p>P_H, high stress group; P_L, low perceived stress; S_H, high state anxiety group; S_L, low state anxiety group;T_H, trait anxiety score; T_L, low trait anxiety; ^bSelf reported economic status; ^c Years; ^d Log₁₀(copies/ml).</p