Plasma Torquetenovirus (TTV) microRNAs and severity of COVID-19

Abstract

Background Torquetenovirus (TTV), a widespread anellovirus recognized as the main component of the healthy human virome, displays viremia that is highly susceptible to variations in immune competence. TTV possesses microRNA (miRNA)-coding sequences that might be involved in viral immune evasion. Among TTV-encoded miRNAs, miRNA t1a, t3b, and tth8 have been found in biological fluids. Here, the presence of TTV DNA and TTV miRNAs in the plasma of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected subjects was investigated to monitor the possible association with coronavirus disease 2019 (COVID-19) severity. Methods Detection of TTV DNA and miRNA t1a, t3b, and tth8 was investigated in plasma samples of 56 SARS-CoV-2-infected subjects with a spectrum of different COVID-19 outcomes. TTV DNA and TTV miRNAs were assessed with a universal single step real-time TaqMan PCR assay and miRNA quantitative RT-PCR miRNA assay, respectively. Results The TTV DNA prevalence was 59%, whereas at least one TTV miRNA was found in 94% of the patients tested. miRNA tth8 was detected in 91% of subjects, followed by miRNAs t3b (64%) and miRNAt1a (30%). Remarkably, although TTV DNA was unrelated to COVID-19 severity, miRNA tth8 was significantly associated with the degree of disease (adjusted incidence rate ratio (IRR) 2.04, 95% CI 1.14–3.63, for the subjects in the high severity group compared to those in the low severity group). Conclusions Our findings encourage further investigation to understand the potential role of TTV miRNAs in the different outcomes of COVID-19 at early and late stages.

TTV viral load as a predictor of antibody response to SARS COV-2 vaccination

“…When combined, TTV DNA load and SARS-CoV-2 viremia allowed to predict the outcome of COVID-19 infection, with a higher risk (HR=12.4) of ICU admission in patients with low TTV DNA load and positive SARS-CoV-2 viremia ( 3 ). Stincarelli et al reported that serum TTV DNA seems unrelated to COVID-19 severity, while TTV miRNA tth8 seems related ( 4 ). At the other end of the spectrum, Emmel et al found that the 100-day survival rate in cancer patients who died from COVID-19 was significantly lower in the TTV-positive group than in the TTV-negative group (P = 0.0475), and that in the cancer TTV-positive group, those who died also had a higher load of TTV than those who did not die (P = 0.0097) ( 5 ).…”

Respiratory torque teno virus load at emergency department visit predicts intensive care unit admission of SARS‐CoV‐2 infected patients

“…However, this association was observed at a time when lymphocyte counts were notably lower in severe cases during the second week after symptom onset 25 . In small group of 56 SARS‐CoV‐2 infected patients, Stincarelli et al did not observe a correlation between TTV load in plasma and disease severity but identified a significant association between severe progression and TTV miRNA tth8 26 …”

“…week period between severe and mild-moderate SARS-CoV-2 cases, Solis et al demonstrated that a TTV DNA load lower than 700 copies/mL was linked to a higher risk of severe COVID-19.However, this association was observed at a time when lymphocyte counts were notably lower in severe cases during the second week after symptom onset 25. In small group of 56 SARS-CoV-2 infected patients, Stincarelli et al did not observe a correlation between TTV load in plasma and disease severity but identified a significant association between severe progression and TTV miRNA tth8 26. F I G U R E 1 Probability of ICU admission according to TTV load.…”

The mysterious anelloviruses: investigating its role in human diseases

“…Based on what previous studies show us, the aforementioned v-miRNAs can be identified and reported in both viremic and non-viremic individuals. ttv-miRNAs are involved in escaping from the host's immune system, viral reactivation, as well as pathogenicity, and finally maintaining chronic viral infection and helping the virus in these processes [ 65 , 75 , 76 ]. TTV uses the cellular miRNA-making machinery to encode and synthesize its viral miRNAs and use them to activate or inhibit specific intracellular signaling pathways [ 77 ].…”

“…The amount of viral load of TTV in the plasma of people with AIDS shows a noticeable decrease after starting the treatment of these patients [ 155 ]. TTV-specific miRNAs were observed in the plasma and cerebrospinal fluid of patients infected with HIV, HCV, or HBV [ 65 ]. Also, high TTMV DNA load has been observed in tissues such as bone marrow and spleen of people who are HIV positive or have progressed to AIDS [ 12 ].…”