Long COVID treated successfully with antivirals in a rituximab-treated follicular lymphoma patient with persistent negative-antibodies to SARS-CoV2

Abstract:

Long COVID is a well-known complication to COVID-19 that affect millions of people worldwide and causes wide range of symptoms. We present a rare case of a previously diagnosed follicular lymphoma patient, who had a long COVID with persistent negative SARS-CoV-2 antibodies and required an aggressive antiviral treatment.

Source: Tayar E, Isber R, Isber N. Long COVID treated successfully with antivirals in a rituximab-treated follicular lymphoma patient with persistent negative-antibodies to SARS-CoV2. Heliyon. 2023 Jun;9(6):e17149. doi: 10.1016/j.heliyon.2023.e17149. Epub 2023 Jun 21. PMID: 37378376; PMCID: PMC10284434. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284434/ (Full text)

Impact of Polypharmacy on Candidate Biomarker miRNomes for the Diagnosis of Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Striking Back on Treatments

Abstract:

Fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are diseases of unknown etiology presenting complex and often overlapping symptomatology. Despite promising advances on the study of miRNomes of these diseases, no validated molecular diagnostic biomarker yet exists. Since FM and ME/CFS patient treatments commonly include polypharmacy, it is of concern that biomarker miRNAs are masked by drug interactions.

Aiming at discriminating between drug-effects and true disease-associated differential miRNA expression, we evaluated the potential impact of commonly prescribed drugs on disease miRNomes, as reported by the literature. By using the web search tools SM2miR, Pharmaco-miR, and repoDB, we found a list of commonly prescribed drugs that impact FM and ME/CFS miRNomes and therefore could be interfering in the process of biomarker discovery. On another end, disease-associated miRNomes may incline a patient’s response to treatment and toxicity.

Here, we explored treatments for diseases in general that could be affected by FM and ME/CFS miRNomes, finding a long list of them, including treatments for lymphoma, a type of cancer affecting ME/CFS patients at a higher rate than healthy population. We conclude that FM and ME/CFS miRNomes could help refine pharmacogenomic/pharmacoepigenomic analysis to elevate future personalized medicine and precision medicine programs in the clinic.

Source: Almenar-Pérez E, Sánchez-Fito T, Ovejero T, Nathanson L, Oltra E. Impact of Polypharmacy on Candidate Biomarker miRNomes for the Diagnosis of Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Striking Back on Treatments. Pharmaceutics. 2019 Mar 18;11(3). pii: E126. doi: 10.3390/pharmaceutics11030126. https://www.mdpi.com/1999-4923/11/3/126 (Full article)

 

A computational analysis of Canale-Smith syndrome: chronic lymphadenopathy simulating malignant lymphoma

Abstract:

OBJECTIVE: The objective of this study was to simulate changes in the human T cell system representing Canale-Smith syndrome using a dynamic computer model of T cell development and comparing with available human data.

STUDY DESIGN: Physiological stepwise maturation and function of T lymphocytes in the computer model is altered by introducing functional disturbances following lymphotropic virus infection. In the present model, acute and chronic persistent infection with the human herpesvirus-6 (HHV-6) was simulated, and ensuing changes in T cell populations were compared with those measured in human patients.

RESULTS: Using our computer model we previously found that simulated acute HHV-6 infection produced T cell computer data, which resembled an infectious mononucleosis-like disease in patients. Simulated chronic persistent infection, instead, resulted in variable cell changes comparing well to patients with chronic fatigue syndrome. In one setting, however, persistent immature lymphocytosis was observed similar to what initial has been described in this journal as Canale-Smith syndrome.

CONCLUSION: Using a computer model developed by us we were able to produce simulations that resemble the immune system features of Canale-Smith syndrome. Further understanding of these simulation results may possibly guide future investigations into this disorder.

 

Source: Krueger GR, Brandt ME, Wang G, Berthold F, Buja LM. A computational analysis of Canale-Smith syndrome: chronic lymphadenopathy simulating malignant lymphoma. Anticancer Res. 2002 Jul-Aug;22(4):2365-71. http://www.ncbi.nlm.nih.gov/pubmed/12174928

 

The disease associations of the antibody response against the Epstein-Barr virus transactivator protein ZEBRA can be separated into different epitopes

Abstract:

The BamHI-Z-encoded Epstein-Barr virus (EBV) replication activator (ZEBRA) is a key mediator of the switch from latency to productive cycle in EBV virus. Antibodies against ZEBRA are a marker of EBV reactivation and are regularly found among patients with infectious mononucleosis (IM) or nasopharyngeal carcinoma (NPC), but are only rarely found among healthy EBV-seropositive donors.

In order to define the serologically reactive epitopes in the ZEBRA protein, we synthesized a set of overlapping peptides and tested them for reactivity with serum samples from EBV-seronegative persons, patients with NPC, IM, chronic fatigue syndrome, lymphoma or from healthy donors. Three major EBV-specific epitopes were found.

These epitopes were further defined and optimized using substitution or truncation analogues of the peptides. Reactivity with epitope number 22 was found in 63% of NPC patients’ sera, with < 2% of healthy donors’ sera being positive. Serological reactivity with epitope number 19 was associated with IM (57% positive, 5% healthy donors positive).

Serum antibodies against epitope 1 were found among healthy donors, but were significantly elevated among patients with NPC, IM or lymphomas. In conclusion, different serologically reactive epitopes in the ZEBRA protein associate with different EBV-associated diseases.

 

Source: Tedeschi R, Foong YT, Cheng HM, dePaoli P, Lehtinen T, Elfborg T, Dillner J. The disease associations of the antibody response against the Epstein-Barr virus transactivator protein ZEBRA can be separated into different epitopes. J Gen Virol. 1995 Jun;76 ( Pt 6):1393-400. http://www.ncbi.nlm.nih.gov/pubmed/7540196

Note: You can read the full study HERE.

 

Antibodies to Epstein-Barr virus-specific DNase and DNA polymerase in the chronic fatigue syndrome

Abstract:

In an attempt to examine further the association between active Epstein-Barr virus (EBV) infection and the chronic fatigue syndrome (chronic EBV syndrome, or chronic or atypical mononucleosis), antibodies acting against EBV-specific DNase and DNA polymerase, which are expressed only during virus replication, were assayed.

Serum samples from 25 healthy EBV-seropositive individuals neutralized 3.5 +/- 5.1 U (mean +/- SD) of DNase activity and 14.7 +/- 8.5 U of DNA polymerase activity. From these values were selected upper limits of anti-EBV enzyme activity of 17.9 and 31.3 U neutralized in normal individuals, respectively (representing the 95% confidence limit). Serum samples from six groups of subjects representing a variety of EBV-related illnesses were then studied.

Only patients with notably elevated anti-EBV antibody titers to viral capsid antigen (VCA) (greater than 10,000) had elevated levels of anti-EBV DNase (38 to 56 U neutralized) and anti-EBV DNA polymerase (72 to 106 U neutralized). Three additional patients and two geriatric controls with average anti-EBV early antigen/VCA titers had slightly elevated levels of antibody to EBV DNA polymerase. IgA anti-VCA, anti-early antigen antibodies, or both, were also detected in the same patients who had high EBV DNase and polymerase antibody levels.

These antibody profiles are similar to those in patients with nasopharyngeal carcinoma. Since three of the six patients with elevated anti-EBV enzyme antibody levels developed fatal lymphomas, patients with chronic EBV and this antibody profile might be in another illness category at risk for malignant disease.

 

Source: Jones JF, Williams M, Schooley RT, Robinson C, Glaser R. Antibodies to Epstein-Barr virus-specific DNase and DNA polymerase in the chronic fatigue syndrome. Arch Intern Med. 1988 Sep;148(9):1957-60. http://www.ncbi.nlm.nih.gov/pubmed/2843138