Study Shows That Those Infected With SARS-CoV-2 Also Manifest High Viral Loads Of Torque Teno Virus (TTV) Which Can Also Be Used As A Biomarker

A new study by Brazilian researchers from the University of Sao Paulo has found that individuals infected with SARS-CoV-2 also manifest high viral loads of another virus called Torque Teno Virus (TTV) which can also be used as a biomarker for COVID-19 severity or even recovery.

 
Torque Teno Virus is a small chronically persisting circular negative ssDNA virus reaching near 100% prevalence. It is reported to be a marker for immune function in immunocompromised patients.
 
TTV or Torque Teno Virus is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants.
 
The study team assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status.
 
Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group.
 
The study findings showed that the saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2–4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved.
 
The study team proposed that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis.
The study findings were published in the peer reviewed journal: PLOS One.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256357
 
The Torque Teno virus (TTV) is one of the viruses most frequently found in the human organism. It is also common in monkeys and domestic animals. Its presence has not been associated with any known disease, but its excessive replication is a sign that something is wrong with the immune system.
 
Importantly the correlation between high TTV load and immunosuppression has been used in medicine in certain contexts, such as monitoring transplant patients who take medication to prevent rejection of the transplanted organ.
 
The study team suggests that TTV load in individuals infected by SARS-CoV-2 can be used as a marker of COVID-19 severity and recovery.
 
First author Dr Maria Cássia Mendes-Correa, a professor at the Medical School (FM-USP), University of Sao Paulo told Thailand Medical News, "We used analyzed samples from 91 patients diagnosed with SAR S-CoV-2 by RT-PCR, and from 126 people with flu symptoms who tested negative. We found TTV titer to be higher in subjects infected by the novel coronavirus. The higher the titer, the longer they remained sick. Symptoms disappeared as viral load decreased. In uninfected subjects, TTV titer remained stable throughout the symptomatic period."
 
Dr Mendes-Correa heads the Virology Laboratory (LIM52) at the Institute of Tropical Medicine (IMT-USP), where TTV has been analyzed for several years in a variety of contexts. The research line is led by Dr Tania Regina Tozetto-Mendoza, a biologist and second author of the study just published.
 
Dr Tozetto-Mendoza added, "We're studying TTV as a potential biomarker for certain clinical outcomes measured in different biological fluids."
 
The research was conducted under the aegis of the São Caetano Corona Program, an online platform established to organize remote monitoring of inhabitants of São Caetano do Sul (a city in metropolitan São Paulo) with symptoms of COVID-19 by healthcare workers, and home collection of samples for diagnosis.
 
The program is an initiative of the Municipal University of São Caetano do Sul (USCS) in partnership with IMT-USP, the city government, and a startup called Modular Research System (MRS).
 
By detailed analysis of samples from patients treated via this program, the IMT-USP researchers have investigated how elimination of SARS-CoV-2 varies over time in different body fluids, such as blood, urine and saliva. The research is supported by FAPESP.
 
Dr Mendes-Correa further added, "We then had the idea of analyzing TTV load in these samples in order to find out whether it correlated with COVID-19 severity. The results showed that TTV can indeed serve as a marker of the progression and outcome of this disease. The more symptomatic the patient, the higher the TTV load in the sample."
 
All participants included in the study had mild or moderate COVID-19, she explained. TTV and SARS-CoV-2 viral loads were measured in saliva samples.
 
The results of the analysis of the answers to a questionnaire showed that none of the participants had diseases that cause immunosuppression, such as cancer or HIV/AIDS.
 
Dr Mendes-Correa added,"COVID-19 appears to lead to a degree of immunodepression by causing an immune system imbalance, and this favors replication of TTV.”
 
This new discovery has no direct clinical applications, but may in future contribute to improved COVID-19 diagnosis and prognosis.
 
Dr Mendes-Correa said, "We're all looking for ways to obtain rapid and accurate diagnosis. One of the possibilities is to develop a kit that doses several biomarkers of the disease at the same time and then assess the results with the aid of algorithms. Measuring TTV titer is one of several tests that could be included in these algorithms to support diagnosis. This is the direction medicine is going in."
 
It should be noted that increased titers of TTV according to some past studies are associated with increased of other disease conditions and also liver issues.
 
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