Study of the effectiveness of immunotropic therapy of Long-COVID-19 patients with type 6 of human herpes virus reactivation, Zubchenko et al., 2024

rapidboson

Senior Member (Voting Rights)
Introduction. After the acute form of COVID-19, 10 to 30% of patients tend to develop a post-covid syndrome or long-COVID-19. Research is actively being conducted into the causes of long-term COVID-19, one of which may be a violation of the immune response after SARS-CoV2 enters the body as a superantigen and the reactivation of “latent” viruses, in particular, human herpes virus type 6 (HHV6).

Aim. Study of the clinical and virological effectiveness, tolerability, and safety of the medicinal product inosine pranobex in long COVID-19 patients with HHV6 reactivation.

Materials and methods. Anamnestic, clinical, general laboratory, biochemical, molecular genetic studies, and statistical analysis were performed. The study group consisted of 20 patients with long COVID-19 and HHV6 reactivation, 55.0% women and 45.0% men. The control group consisted of 20 practically healthy people of respective age and sex.

Results. The prevalence of HHV6 reactivation in patients with long COVID-19 amounted to 100.0% regardless of the severity of COVID-19 history. The most frequent complaints of patients were increased fatigue in 100.0%; sleep disturbances, constant fatigue, and increased sweating in 85.0%; impaired mobility, headaches, and loss of smell in 80.0%, and others. In patients with long COVID-19 and HHV6 reactivation, changes in the complete blood count were determined compared to the control group of healthy individuals. After the treatment, the patient’s condition and laboratory parameters improved significantly. The clinical effectiveness of treatment with inosine pranobex for 12 weeks generally amounted to 60.1%, and the virological efficacy was 79.4%. Long-term treatment of patients with long COVID-19 and active phase of chronic HHV6 infection with the drug inosine pranobex demonstrated safety and good tolerability.

Conclusions. Treatment of long COVID-19 patients with HHV-6 reactivation with the drug inosine pranobex demonstrated 60.1% clinical and 79.1% virological efficacy, good tolerability, and safety.

LINK PDF
 
The prevalence of HHV6 reactivation in patients with long COVID-19 amounted to 100.0% regardless of the severity of COVID-19 history.
The 100% relationship between Long Covid and HHV6 reactivation is, I assume, because that was the selection criteria.
The study group consisted of 20 patients with long COVID-19 and HHV6 reactivation

So, a question would be 'how common is HHV6 reactivation in Long Covid?'. And, 'how common is HHV6 reactivation in people without Long Covid?'

My other questions would be 'what is clinical effectiveness?', and to what extent did clinical effectiveness and virological efficacy overlap. That is, were all cases of symptom improvement accompanied by control of the virus?

web search said:
Inosine pranobex is a synthetic product, also known as isoprinosine or inosine dimepranol acedobene, with antiviral properties that are assumed to be related to its effect on T cell-mediated immunity rather than to direct antiviral activity. It has been tried in a wide range of viral diseases and also in rheumatoid arthritis [1], multiple sclerosis [2], and alopecia [3]. However, clinical trials have mostly shown only modest therapeutic benefit or none at all [1,4], and no specific adverse effects or reactions, except for an increase in serum uric acid concentrations [5], reflecting the metabolic pathways of purines [6].
 
The virologist I saw did a study with Dr. Byron Hyde on 36 CFS patients who took Imunovir and found that they felt 'less fatigued'.

I on the other hand had a complete relapse after only taking it for less than 3 weeks, it changed the course of my illness to worse when I was feeling 80-90% improved at the time.
 
So, a question would be 'how common is HHV6 reactivation in Long Covid?'.

Seems like they've had a pilot study beforehand?

88 patients were recruited for this study, including subjects with reactivation of herpes viruses, 68 (72.3%) (main group) and 20 (27.7%) subjects without detectable DNA of herpesviruses (control group): 46 (52.3%) female and 42 (47.7%) male; median age was 41.4 ± 6.7 years. Patients with post-COVID manifestations presented with reactivation of EBV in 42.6%, HHV6 in 25.0%, and EBV plus HHV6 in 32.4%. Compared with controls, patients with herpes virus infections presented with more frequent slight fever temperature, headache, psycho-neurological disorders, pulmonary abnormalities and myalgia (p < 0.01), activation of liver enzymes, elevated CRP and D-dimer, and suppressed cellular immune response (p ≤ 0.05).

And a review that seems to address this (haven't read).
 
The 100% relationship between Long Covid and HHV6 reactivation is, I assume, because that was the selection criteria.
I don't see any indication in the text that that's the case:
Inclusion criteria were adults of both sexes aged 18 to 65 with a history of asymptomatic, mild, moderate, or severe COVID-19 and symptoms lasting more than 12 weeks. COVID-19 was confirmed by PCR detection of RNA from nasal/oropharyngeal swabs and antigen rapid tests.

Exclusion criteria: individuals who have suffered from COVID-19 and do not show any long-term complaints, children, pregnant women, HIV-infected patients, patients with autoimmune, oncological, acute infectious and chronic cardiovascular, pulmonary, neurological, lymphoproliferative diseases, diabetes type 1, and type 2, and any other accompanying decompensated diseases, as well as individuals who abuse alcohol, narcotic substances or were exposed to toxic or chemical substances.
All patients were tested for the presence of HHV6 DNA in 3 media. According to PCR data, it was established that in all 100.0% of patients with long-COVID-19, HHV6 DNA was detected in saliva, in 90.0% – in the mucous membrane of the back wall of the pharynx, and in 30.0% – in blood. Thus, the prevalence of HHV6 reactivation in patients with long COVID-19 amounted to 100.0% regardless of the severity of COVID-19 history.
upload_2025-5-14_9-2-33.png
 
@forestglip the abstract makes it look like it:
Hmm, yeah maybe. They didn't make it clear enough in the full text if that is the case.

Edit: Ah actually, it seems they do say they confirm the patients were positive to be included:
To be included in the study and to confirm the presence of HHV6, molecular genetic analyses were performed to detect HHV6 DNA in three environments (blood, saliva, mucosa).
 
Hmm, yeah maybe. They didn't make it clear enough in the full text if that is the case.

Edit: Ah actually, it seems they do say they confirm the patients were positive to be included:
The pdf also says this:
To be included in the study and to confirm the presence of HHV6, molecular genetic analyses were performed to detect HHV6 DNA in three environments (blood, saliva, mucosa).
Either way, they should have been less ambiguous.
 
The pdf also says this:

Either way, they should have been less ambiguous.
Thanks yeah, missed it the first time. So I don't think the decrease in HHV6 is very meaningful here without a long COVID control group. Their patient group might just select for people who had a temporary flare-up of the virus and at the follow-up they were back to normal - regression to the mean. Just glancing at the study @rapidboson posted above, their followup proportion seems to almost exactly match the proportion from the other observational study. I think 45% positive for HHV6 here, and in the other study I get 39 positive out of 88 total = 44.3%.
 
Back
Top