Epstein-Barr virus (EBV) reactivation in COVID-19 patients has been reported, but studies on its clinical significance are lacking. We herein report the occurrence of infectious mononucleosis (IM) ...due to EBV reactivation in a 60-year-old man with rheumatoid arthritis being treated with methotrexate and tocilizumab. The patient presented with a fever and tested positive for COVID-19. Laboratory findings revealed an increased atypical lymphocyte count, decreased platelet count, and elevated liver enzyme levels. Flow cytometry showed predominant expansion of reactive T cells. EBV reactivation was confirmed using real-time polymerase chain reaction. The patient was treated with remdesivir, and clinical improvement was observed after 10 days of treatment. Follow-up showed a gradual decrease in the EBV-DNA load with no recurrence of atypical lymphocytes. These findings suggest that COVID-19 in immunocompromised patients may lead to unexpected EBV reactivation and IM, even for patients outside the age at which IM is likely to occur.
Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become ...known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein–Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p < 0.001, Fisher’s exact test). A similar ratio was observed in a secondary group of 18 subjects 21–90 days after testing positive for COVID-19, indicating reactivation may occur soon after or concurrently with COVID-19 infection. These findings suggest that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of COVID-19 inflammation-induced EBV reactivation.
An 81-year-old man underwent rituximab-containing chemotherapy for chronic lymphocytic leukemia (CLL). Thirteen years after his last chemotherapy, he was diagnosed with hepatitis B virus (HBV) ...reactivation. He was then treated with entecavir, and improvement was seen in his liver injury. He developed diffuse large B cell lymphoma (DLBCL) after improvement in his hepatitis. Despite chemotherapy, he contracted the coronavirus disease 2019 (COVID-19) and died of COVID-19. We suspect that HBV reactivation was triggered by DLBCL. When HBV reactivation occurs a long time after chemotherapy has concluded, the onset of DLBCL should be considered.
Recently, varicella‐zoster virus (VZV) reactivation has been observed after the administration of coronavirus disease 2019 (COVID‐19) vaccines. Autoimmune inflammatory rheumatic diseases (AIIRDs) ...patients are at a higher risk for VZV reactivation for immunocompromised status. The study aimed to investigate the adverse events (AEs), especially VZV reactivation, following vaccination against severe acute respiratory syndrome coronavirus‐2 in a Chinese cohort of AIIRD patients. A cross‐sectional survey using an online questionnaire was conducted among AIIRD patients and healthy controls (HCs). Multivariate logistic regression was used to identify potential factors associated with VZV reactivation. 318 AIIRD patients and 318 age and sex‐matched HCs who got COVID‐19 inactivated vaccines were recruited. The main AIIRDs are rheumatoid arthritis (31.8%) and systemic lupus erythematous (23.9%). Most of patients (85.5%) had stable disease and 13.2% of them had aggravation after vaccination. Compared to HCs, patients had higher rates of rash (p = 0.001), arthralgia (p < 0.001) and insomnia (p = 0.007). In addition, there were 6 (1.9%) AIIRD patients and 5 (1.6%) HCs reported VZV reactivation after the COVID‐19 vaccination (p = 0.761). Multivariate logistic regression analysis illustrated that diabetes mellitus (odd ratio OR, 20.69; 95% confidence interval CI, 1.08−396.79; p = 0.044), chronic hepatitis B virus infection (OR, 24.34; 95% CI, 1.27−466.74; p = 0.034), and mycophenolate mofetil (OR, 40.61; 95% CI, 3.33−496.15; p = 0.004) independently identified patients with VZV reactivation. Our findings showed that the inactivated COVID‐19 vaccination was safe for AIIRD patients though some patients could suffer from VZV reactivation.
The persistence of latent HIV-1 reservoirs in cells presents a formidable challenge towards a complete HIV cure. Edelfosine is an FDA-approved investigational, anti-neoplastic drug. In this study, we ...aimed to investigate its role as a HIV-1 Latency Reversal Agent (LRA) using latency model cell lines. Our findings demonstrated that edelfosine reactivated latent HIV-1 viruses in myeloid cells in a dose and time-dependent manner. The mechanism of reactivation by edelfosine involved the activation of NF-κB and AP1 pathways in these cells. The reactivated virus was non-infectious. Delineating the mechanism of non-infectious virus production revealed an increased stabilization of cellular APOBEC3G protein as well as its enhanced incorporation into the released viruses. Thus, our study demonstrated for the first time an additional role of edelfosine in reactivation of latent HIV-1 and production of non-infectious virus. Our results have paved the way for repurposing of edelfosine as a novel HIV-1 latency reversal agent.
•Edelfosine reactivated latent HIV-1 in myeloid cells in a dose and time-dependent manner.•The mechanism of reactivation involved the activation of NF-κB and AP1 pathways.•The reactivated virus was non-infectious due to enhanced APOBEC3G packaging.•Our results shows edelfosine may be repurposed as a novel LRA.
The risk of hepatitis B virus (HBV) reactivation remains unclear in people with multiple sclerosis (MS) receiving ocrelizumab. We aimed to assess HBV seroprevalence and reactivation risk in MS ...patients on ocrelizumab and to evaluate the effectiveness of antiviral prophylaxis against HBV reactivation.
In this single-center, cross-sectional study, 400 people with MS receiving ocrelizumab were screened for HBV at baseline and antiviral prophylaxis was implemented based on serological results. Patients were monitored for HBV reactivation, and outcomes were analyzed.
Among 56 (14%) patients who had serology compatible with occult or resolved HBV infection, 49 (85.7%) received antiviral prophylaxis regularly and had no HBV reactivation during the follow-up. Reactivation of HBV occurred in 2 out of 7 (28.6%) patients who did not receive antiviral prophylaxis and in one patient who did not adhere to the prophylaxis regimen. All patients with reactivation had anti-HBs levels below 100 mIU/mL and the median titer was significantly lower than the patients with no HBV reactivation (p = 0.034).
This study highlights a 14% anti-HBc positivity, indicating a potential risk for HBV reactivation in people with MS receiving ocrelizumab. This suggests the importance of vigilant monitoring and the implementation of prophylactic measures. Our recommendation emphasizes antiviral prophylaxis, particularly for patients with low anti-HBs, and a pre-emptive strategy for others.
An 88-year-old man was admitted for elevated liver enzyme levels. Nine years earlier, the patient had been diagnosed with diffuse large B-cell lymphoma (DLBCL) and undergone rituximab, ...cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisone (R-CHOP) therapy. This patient previously had had a hepatitis B virus (HBV) infection before chemotherapy. After the chemotherapy, he was administered an LHRH agonist for prostate cancer. We diagnosed him with HBV reactivation because of positive serum HBV-DNA. HBV reactivation can occur a long time after chemotherapy, particularly if another treatment with immunity-altering drugs is added. In such cases, additional surveillance may be required to detect HBV reactivation.
Nanoparticles (NPs) released from engineered materials or combustion processes as well as persistent herpesvirus infection are omnipresent and are associated with chronic lung diseases. Previously, ...we showed that pulmonary exposure of a single dose of soot-like carbonaceous NPs (CNPs) or fiber-shaped double-walled carbon nanotubes (DWCNTs) induced an increase of lytic virus protein expression in mouse lungs latently infected with murine γ-herpesvirus 68 (MHV-68), with a similar pattern to acute infection suggesting virus reactivation. Here we investigate the effects of a more relevant repeated NP exposure on lung disease development as well as herpesvirus reactivation mechanistically and suggest an avenue for therapeutic prevention. In the MHV-68 mouse model, progressive lung inflammation and emphysema-like injury were detected 1 week after repetitive CNP and DWCNT exposure. NPs reactivated the latent herpesvirus mainly in CD11b+ macrophages in the lungs. In vitro, in persistently MHV-68 infected bone marrow-derived macrophages, ERK1/2, JNK, and p38 MAPK were rapidly activated after CNP and DWCNT exposure, followed by viral gene expression and increased viral titer but without generating a pro-inflammatory signature. Pharmacological inhibition of p38 activation abrogated CNP- but not DWCNT-triggered virus reactivation in vitro, and inhibitor pretreatment of latently infected mice attenuated CNP-exposure-induced pulmonary MHV-68 reactivation. Our findings suggest a crucial contribution of particle-exposure-triggered herpesvirus reactivation for nanomaterial exposure or air pollution related lung emphysema development, and pharmacological p38 inhibition might serve as a protective target to alleviate air pollution related chronic lung disease exacerbations. Because of the required precondition of latent infection described here, the use of single hit models might have severe limitations when assessing the respiratory toxicity of nanoparticle exposure.
Drug hypersensitivity reactions (DHR) are heterogeneous and unusual immune reactions with rather unique clinical presentations. Accumulating evidence indicates that certain non‐covalent drug‐protein ...interactions are able to elicit exclusively effector functions of antibody reactions or complete T‐cell reactions which contribute substantially to DHR. Here, we discuss three key interactions; (a) mimicry: whereby soluble, non‐covalent drug‐protein complexes (“fake antigens”) mimic covalent drug‐protein adducts; (b) increased antibody affinity: for example, in quinine‐type immune thrombocytopenia where the drug gets trapped between antibody and membrane‐bound glycoprotein; and (c) p‐i‐stimulation: where naïve and memory T cells are activated by direct binding of drugs to the human leukocyte antigen and/or T‐cell receptors. This transient drug‐immune receptor interaction initiates a polyclonal T‐cell response with mild‐to‐severe DHR symptoms. Notable complications arising from p‐i DHR can include viral reactivations, autoimmunity, and multiple drug hypersensitivity. In conclusion, DHR is characterized by abnormal immune stimulation driven by non‐covalent drug‐protein interactions. This contrasts DHR from “normal” immunity, which relies on antigen‐formation by covalent hapten‐protein adducts and predominantly results in asymptomatic immunity.
Hepatitis B virus reactivation (HBV-R), which can lead to HBV-related morbidity and mortality, is a common and well-known complication that occurs during the treatment of non-Hodgkin lymphoma (NHL) ...patients with current or past exposure to HBV infection. HBV-R is thought to be closely associated with chemotherapeutic or immunosuppressive therapies. However, immunosuppressive agents such as anti-CD20 antibodies (e.g., rituximab and ofatumumab), glucocorticoids, and hematopoietic stem cell transplantation (HSCT) administered to NHL patients during treatment can cause deep immunodepression and place them at high risk of HBV-R. In this review, we explore the current evidence, the guidelines of several national and international organizations, and the recommendations of expert panels relating to the definition, risk factors, screening and monitoring strategies, whether to use prophylaxis or pre-emptive therapy, and the optimal antiviral agent and duration of antiviral therapy for HBV-R.
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