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1.
J Nanobiotechnology ; 20(1): 335, 2022 Jul 16.
Article in English | MEDLINE | ID: covidwho-1935529

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals, including transplant recipients and Acquired Immune Deficiency Syndrome patients. Antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity. METHODS: The antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo. RESULTS: MPDGP showed significant inflammation tropism and efficient suppression of viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects of the combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently. CONCLUSION: The present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cell to deliver antiviral drugs for pneumonia treatment.


Subject(s)
Antiviral Agents , Nanoparticle Drug Delivery System , Pneumonia/drug therapy , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cytomegalovirus , Cytomegalovirus Infections/drug therapy , Fatty Acids, Monounsaturated/chemistry , Foscarnet/pharmacology , Foscarnet/therapeutic use , Ganciclovir/pharmacology , Ganciclovir/therapeutic use , Humans , Inflammation/drug therapy , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Quaternary Ammonium Compounds/chemistry , Stem Cells
2.
Transpl Int ; 35: 10332, 2022.
Article in English | MEDLINE | ID: covidwho-1933951

ABSTRACT

Infections are leading causes of morbidity/mortality following solid organ transplantation (SOT) and cytomegalovirus (CMV) is among the most frequent pathogens, causing a considerable threat to SOT recipients. A survey was conducted 19 July-31 October 2019 to capture clinical practices about CMV in SOT recipients (e.g., how practices aligned with guidelines, how adequately treatments met patients' needs, and respondents' expectations for future developments). Transplant professionals completed a ∼30-minute online questionnaire: 224 responses were included, representing 160 hospitals and 197 SOT programs (41 countries; 167[83%] European programs). Findings revealed a heterogenous approach to CMV diagnosis and management and, sometimes, significant divergence from international guidelines. Valganciclovir prophylaxis (of variable duration) was administered by 201/224 (90%) respondents in D+/R- SOT and by 40% in R+ cases, with pre-emptive strategies generally reserved for R+ cases: DNA thresholds to initiate treatment ranged across 10-10,000 copies/ml. Ganciclovir-resistant CMV strains were still perceived as major challenges, and tailored treatment was one of the most important unmet needs for CMV management. These findings may help to design studies to evaluate safety and efficacy of new strategies to prevent CMV disease in SOT recipients, and target specific educational activities to harmonize CMV management in this challenging population.


Subject(s)
COVID-19 , Cytomegalovirus Infections , Organ Transplantation , Antiviral Agents/therapeutic use , Cytomegalovirus , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/prevention & control , Ganciclovir/therapeutic use , Humans , Organ Transplantation/adverse effects , Surveys and Questionnaires , Transplant Recipients
3.
Immun Inflamm Dis ; 10(4): e597, 2022 04.
Article in English | MEDLINE | ID: covidwho-1739166

ABSTRACT

BACKGROUND: Systemic reactivation of Epstein-Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the clinical consequences of EBV reactivation remain uncertain. METHODS: In this retrospective study, we screened 1314 patients with confirmed COVID-19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)-immunoglobulin G (IgG), Epstein-Barr nuclear antigen-IgG, VCA-IgM, early antigen (EA)-IgG, CMV-IgG, and CMV-IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics. RESULTS: EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p < .001), female gender (31 [56%] vs. 60 [37%], p = .02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], p = .08). EA-IgG levels were significantly higher in nonsurvivors than in survivors (median difference: -0.00005, 95% confidence interval, CI [-3.10, 0.00], p = .05). As compared to patients with COVID-19 who did not receive ganciclovir therapy, ganciclovir-treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], p = .01). Hemoglobin (p < .001) and prealbumin (p = .02) levels were significantly higher in ganciclovir-treated patients. CONCLUSION: A high proportion of COVID-19 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID-19 patients complicated with EBV reactivation warrants to be addressed in a placebo-controlled randomized trial in the future.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , COVID-19/drug therapy , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/drug therapy , Female , Ganciclovir/therapeutic use , Herpesvirus 4, Human/physiology , Humans , Retrospective Studies , SARS-CoV-2
4.
J Neuroimmunol ; 353: 577521, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1091758

ABSTRACT

BACKGROUND: Serious neurological complications of SARS-CoV-2 are increasingly being recognized. CASE: We report a novel case of HHV6 myelitis with parainfectious MOG-IgG in the setting of COVID-19-induced lymphopenia and hypogammaglobulinemia. The patient experienced complete neurological recovery with gancyclovir, high dose corticosteroids, and plasma exchange. To our knowledge, this is the first case of HHV6 reactivation in the central nervous system in the setting of COVID19 infection and the first case of MOG-IgG myelitis in the setting of SARS-CoV-2 and HHV6 coinfection. CONCLUSION: Patients with neurological manifestations in the setting of COVID19-related immunodeficiency should be tested for opportunistic infections including HHV6. Viral infection is a known trigger for MOG-IgG and therefore this antibody should be checked in patients with SARS-CoV-2 associated demyelination.


Subject(s)
COVID-19/complications , Coinfection/complications , Lymphopenia/virology , Myelitis, Transverse/virology , Roseolovirus Infections/immunology , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Autoantibodies/immunology , Autoantigens/immunology , COVID-19/immunology , Coinfection/immunology , Ganciclovir/therapeutic use , Herpesvirus 6, Human , Humans , Male , Methylprednisolone/therapeutic use , Middle Aged , Myelitis, Transverse/immunology , Myelitis, Transverse/therapy , Plasma Exchange/methods , Roseolovirus Infections/drug therapy , SARS-CoV-2 , Virus Activation/immunology
5.
Cornea ; 40(3): 383-386, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1066450

ABSTRACT

PURPOSE: To present a patient with bilateral conjunctivitis, testing positive for viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in both nasopharyngeal and conjunctival samples. METHODS: A 40-year-old man with bilateral acute conjunctivitis and suspicious signs of coronavirus disease 2019 (COVID-19) presented to the hospital. A detailed ophthalmic examination was performed. Samples obtained from conjunctival and nasopharyngeal swabs were tested by reverse transcription PCR (RT-PCR) for the detection of SARS-CoV-2 virus. Ocular findings and duration of the presence of viral RNA in the conjunctival specimens were evaluated at follow-up visits. RESULTS: Slit-lamp biomicroscopy revealed bilateral acute follicular conjunctivitis. The RT-PCR assay demonstrated the presence of viral RNA in the nasopharyngeal and conjunctival specimens at the initial visit and at the 4-day follow-up. Conjunctivitis findings were decreased after 4 days and recovered completely without any sequelae within10 days. The PCR results of both nasopharyngeal and conjunctiva specimens were negative for the viral RNA at 10 days. CONCLUSIONS: Bilateral conjunctivitis is rare in patients infected with COVID-19. Although it is difficult to detect viral RNA from conjunctival swabs, conjunctival secretions may be a source of contamination, and protective measures must be taken.


Subject(s)
COVID-19/virology , Conjunctiva/virology , Conjunctivitis, Viral/virology , Eye Infections, Viral/virology , Nasopharynx/virology , RNA, Viral/genetics , SARS-CoV-2/isolation & purification , Administration, Ophthalmic , Administration, Oral , Adult , Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Nucleic Acid Testing , Conjunctivitis, Viral/diagnosis , Conjunctivitis, Viral/drug therapy , Drug Therapy, Combination , Eye Infections, Viral/diagnosis , Eye Infections, Viral/drug therapy , Ganciclovir/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Intraocular Pressure , Male , Pharmaceutic Aids/therapeutic use , Povidone/therapeutic use , SARS-CoV-2/genetics , Slit Lamp Microscopy , Visual Acuity
6.
J Cataract Refract Surg ; 46(12): e61-e63, 2020 12.
Article in English | MEDLINE | ID: covidwho-910345

ABSTRACT

This case report describes a negative result for antigen testing for the SARS-CoV-2 virus in an aqueous sample taken during the management of suspected herpes simplex keratitis from a patient with confirmed SARS-CoV-2 based on antigen testing of high nasal swab. The implications of no viral load detectable in the aqueous sample are discussed in context of routine phacoemulsification surgery during the SARS-CoV-2 pandemic.


Subject(s)
Aqueous Humor/virology , COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Corneal Stroma/virology , Keratitis, Herpetic/diagnosis , SARS-CoV-2/isolation & purification , Antiviral Agents/therapeutic use , COVID-19/genetics , COVID-19/virology , Ganciclovir/therapeutic use , Humans , Keratitis, Herpetic/drug therapy , Keratitis, Herpetic/virology , Male , Middle Aged , Recurrence , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , Simplexvirus/pathogenicity , Visual Acuity/physiology
7.
Antiviral Res ; 180: 104857, 2020 08.
Article in English | MEDLINE | ID: covidwho-602131

ABSTRACT

SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 worldwide pandemic. We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine. We report here the evaluation of a library of nucleoside triphosphate analogues with a variety of structural and chemical features as inhibitors of the RdRps of SARS-CoV and SARS-CoV-2. These features include modifications on the sugar (2' or 3' modifications, carbocyclic, acyclic, or dideoxynucleotides) or on the base. The goal is to identify nucleotide analogues that not only terminate RNA synthesis catalyzed by these coronavirus RdRps, but also have the potential to resist the viruses' exonuclease activity. We examined these nucleotide analogues for their ability to be incorporated by the RdRps in the polymerase reaction and to prevent further incorporation. While all 11 molecules tested displayed incorporation, 6 exhibited immediate termination of the polymerase reaction (triphosphates of Carbovir, Ganciclovir, Stavudine and Entecavir; 3'-OMe-UTP and Biotin-16-dUTP), 2 showed delayed termination (Cidofovir diphosphate and 2'-OMe-UTP), and 3 did not terminate the polymerase reaction (2'-F-dUTP, 2'-NH2-dUTP and Desthiobiotin-16-UTP). The coronaviruses possess an exonuclease that apparently requires a 2'-OH at the 3'-terminus of the growing RNA strand for proofreading. In this study, all nucleoside triphosphate analogues evaluated form Watson-Crick-like base pairs. The nucleotide analogues demonstrating termination either lack a 2'-OH, have a blocked 2'-OH, or show delayed termination. Thus, these nucleotide analogues are of interest for further investigation to evaluate whether they can evade the viral exonuclease activity. Prodrugs of five of these nucleotide analogues (Cidofovir, Abacavir, Valganciclovir/Ganciclovir, Stavudine and Entecavir) are FDA-approved medications for treatment of other viral infections, and their safety profiles are well established. After demonstrating potency in inhibiting viral replication in cell culture, candidate molecules can be rapidly evaluated as potential therapies for COVID-19.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus Infections/virology , Nucleotides/pharmacology , Pneumonia, Viral/virology , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Severe Acute Respiratory Syndrome/virology , /enzymology , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Betacoronavirus/enzymology , Betacoronavirus/genetics , COVID-19 , Cidofovir/chemistry , Cidofovir/pharmacology , Cidofovir/therapeutic use , Coronavirus Infections/drug therapy , Dideoxynucleosides/chemistry , Dideoxynucleosides/pharmacology , Dideoxynucleosides/therapeutic use , Ganciclovir/chemistry , Ganciclovir/pharmacology , Ganciclovir/therapeutic use , Guanine/analogs & derivatives , Guanine/chemistry , Guanine/pharmacology , Guanine/therapeutic use , Nucleotides/chemistry , Nucleotides/therapeutic use , Pandemics , Pneumonia, Viral/drug therapy , Prodrugs/chemistry , Prodrugs/pharmacology , Prodrugs/therapeutic use , RNA, Viral/antagonists & inhibitors , RNA, Viral/biosynthesis , SARS-CoV-2 , Severe Acute Respiratory Syndrome/drug therapy , Stavudine/chemistry , Stavudine/pharmacology , Stavudine/therapeutic use , Valganciclovir/chemistry , Valganciclovir/pharmacology , Valganciclovir/therapeutic use
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