Sequential activation of DNA viruses by the RNA virus SARS-CoV-2 in patients with long COVID syndrome

Abstract:

Background: Reactivation of Epstein-Barr virus (EBV) has been suggested to play role in long lasting multiorgan symptoms several months after the initial COVID-19 illness.
Purpose: The aim of our prospective study was to 1) to evaluate the reactivation of DNA viruses of EBV, Cytomegalovirus, Herpes simplex, Varicella zoster and Parvovirus-B19 by SARS-CoV-2 in patients with the diagnosis of long-COVID syndrome, 2) to investigate the effect of supposed virus reactivation on clinical conditions and long COVID syndromes.
Methods: Patients with long COVID syndrome were prospectively included into the Vienna PostCoV Registry between March 15th 2021 and September 30th 2021. – The time between COVID-19 infection and first clinical visit was 219±98 days (7±3 months). Clinical symptoms were documented and patients were divided into symptoms-oriented subgroups with dominantly respiratory, cardiovascular or neuropsychologic complaints. Qualitative and quantitative viral IgG and IgM titer of the selected DNA viruses of n=105 patients were compared with age and sex-matched healthy (non-infected, non-vaccinated, n=105) controls, who had neither spike- nor nucleocapsid antibodies, nor clinical history of COVID-19 disease.
Results: Long Covid patients had significantly higher cumulative number of IgM positivity of the DNA viruses (18.1% vs 6.7%, p=0.02), and significantly elevated quantitative EBV IgG (420±296 vs 339±282 mg/dL, p=0.033) and Parvo-B19 IgM (0.28±0.29 vs 0.03±0.12 mg/dL, p<0.001) titer as compared to healthy controls. Significantly more patients with long COVID symptoms had an EBV IgG titer above the detection limit as compared with healthy controls (40% vs 28%, p=0.018), suggesting EBV virus reactivation and chronic EBV infection. EBV IgG titer was significantly higher in patients with dominant respiratory symptoms, while elevated Parvo-B19 IgM titer was observed in patients with dominant cardiovascular complaints. In patients with long-COVID syndrome the quantitative EBV IgG titer increased with the time between infection and blood sampling (logarithmic correlation, p=0.011), suggesting the subclinical continuous EBV activation by the SARS-CoV2 RNA virus, while the quantitative Parvo-B19 IgM titer decreased linearly during the observation period
Conclusions: In this study of patients with long-COVID syndrome, SARS-CoV-2 infection apparently activated certain types of DNA viruses (EBV, and Parvo-B19), as demonstrated by the significantly higher incidence of cumulative IgM positivity, and elevated EBV IgG and parvovirus-B19 IgM titers, in long-COVID patients compared to healthy controls.
Source: M Gyongyosi, E Hasimbegovic, D Lukovic, K Zlabinger, A Spannbauer, E Samaha, J Bergler-Klein, C Hengstenberg, P Mucher, H Haslacher, M Breuer, R Strassl, M Riesenhuber, C Nitsche, T A Zelniker, Sequential activation of DNA viruses by the RNA virus SARS-CoV-2 in patients with long COVID syndrome, European Heart Journal, Volume 44, Issue Supplement_2, November 2023, ehad655.1823, https://doi.org/10.1093/eurheartj/ehad655.1823 https://academic.oup.com/eurheartj/article/44/Supplement_2/ehad655.1823/7393979 (Full text available as PDF file)

Comprehensive profiling of the human intestinal DNA virome and prediction of disease-associated bacterial hosts in severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disorder of unknown etiology with severely affected patients being house- and/or bedbound. A historical association with chronic virus infection and subsequent recent reports correlating intestinal microbial dysbiosis with disease pathology prompted us to analyze the intestinal virome in a small cohort of severely-affected ME/CFS patients and same household healthy controls (SHHC).

Datasets from whole metagenomic sequencing (WMS) and sequencing of virus-like particles (VLP)-enriched metagenomes from the same fecal sample yielded diverse, high-quality vOTUs with high read coverage and high genome completeness. The core intestinal virome was largely composed of tailed phages in the class Caudoviricetes with no significant differences in alpha diversity between ME/CFS and SHHC groups. However, the WMS dataset had a higher Shannon measure than the VLP dataset (p < 0.0001), with VLP- and WMS-derived sequences indicating differential abundances within several viral families and different viral compositions in beta diversity.

This confirms that combining different isolation methodologies identifies a greater diversity of viruses including extracellular phages and integrated prophages. DNA viromes and bacteriomes from ME/CFS and SHHC groups were comparable with no differences in any alpha or beta diversity measures. One vOTU derived from the VLP-derived dataset was assigned to ssDNA human virus smacovirus 1. Using an in-silico approach to predict cohort-based bacterial hosts, we identified members of the Anaerotruncus genus interacting with unique viruses present in ME/CFS microbiomes; this may contribute to the GI microbial dysbiosis described in ME/CFS patients.

Source: Shen-Yuan HsiehGeorge M SavvaAndrea TelatinSumeet K TiwariMohammad A TariqFiona NewberryKatharine A SetonCatherine BoothAmolak S BansalTom WilemanEvelien AndriaenssensSimon R Carding. Comprehensive profiling of the human intestinal DNA virome and prediction of disease-associated bacterial hosts in severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).