ABSTRACT
Background: Previous studies have demonstrated promising serologic responses in PLWH receiving a third dose of vaccine against SARS-CoV-2. However, real-world clinical effectiveness, especially during the pandemic caused by B.1.1.529 variant, remains less investigated. Method(s): PLWH seeking HIV care at our hospital from 2021/6 to 2022/6 were included and advised to receive the third dose of COVID-19 vaccine. Individuals were excluded from this study if they had been previously diagnosed with COVID-19. Different types of COVID-19 vaccines were available in the vaccination program, including BNT162b2, mRNA-1273 (either 50 or 100 mug), MVC-COV1901 and NVX-CoV2373 vaccines. PLWH were screening for the occurrence of COVID-19 through the reporting system of notifiable diseases of Taiwan CDC, and were tested for anti-nucleocapsid (anti-N) IgG every 1 to 3 months. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, occurrence of SARS-CoV-2 infection, seroconversion of anti-N IgG, death, or loss to follow-up, whichever occurred first. Result(s): 1,496 PLWH were included: 631 (42.2%) receiving 100 mug mRNA-1273 vaccine, 468 (31.3%) 50 mug mRNA-1273 vaccine, and 328 (21.9%) BNT162b2 vaccine, 65 (4.3%) MVC-COV1901 vaccine, and 4 (0.3%) NVX-CoV2373 vaccine for the third dose of SARS-CoV-2 vaccination. 297 (19.9%) PLWH were diagnosed with COVID-19 during the follow-up period, including 92 (14.6%) who received 100 mug mRNA-1273, 111 (23.7%) 50 mug mRNA-1273, 79 (24.1%) BNT162b2 and 15 (21.7%) either MVC-COV1901 or NVX-CoV2373;in addition, 98 PLWH had seroconversion of anti-N IgG during follow-up, including 23, 50, 19 and 6 PLWH who received 100 mug mRNA-1273, 50 mug mRNA-1273, BNT162b2, and either MVC-COV1901 or NVX-CoV2373, respectively. Similar rates of new infection with SARS-CoV-2 or seroconversion of anti-N IgG were demonstrated regardless the vaccine type of the third dose (log-rank test, p=0.46). Factors associated with a diagnosis of SARS-CoV-2 infection and seroconversion of anti-N IgG included an age >50 years (aOR, 0.67;95% CI, 0.49-0.91) and newly infected with hepatitis C virus (HCV) (aOR, 1.41;95% CI, 1.09-1.83). Conclusion(s): Our study demonstrated that clinical effectiveness of the third dose of different vaccines available to PLWH was similar in preventing SARSCoV- 2 infection or seroconversion of anti-N IgG Taiwan. PLWH aged less than 50 years and those with newly diagnosed HCV infection were at higher risk of acquiring COVID-19. Kaplan-Meier survival curve for acquiring COVID-19 or seroconversion of anti-N IgG in PLWH receiving different COVID-19 vaccination of the third dose (log-rank test, 4 groups, p = 0.46).
ABSTRACT
Background: Previous studies had demonstrated that patients with hematologic malignancies had suboptimal antibody response after receiving COVID-19 vaccines, especially among those having previously treated with anti- CD20 monoclonal antibodies. Method(s): Adult patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia (CLL) were enrolled before receiving the second dose of SARS-CoV-2 vaccine. Determinations of anti-SARS-CoV-2 spike and nucleocapsid IgG titers were performed every 1-3 months, after they received the second and the third dose of SARS-CoV-2 vaccine, respectively. Patients were excluded from analysis if they were diagnosed with COVID-19. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from subsequent analyses. Result(s): A total of 85 participants were enrolled, including 42 (49.4%) with diffused large B-cell lymphoma, and 13 (15.3) with follicular lymphoma and 9 with CLL. 72 (84.7%) participants had received anti-CD20 monoclonal antibodies, with a median interval of 24 months between last anti-CD20 treatment and the second dose of vaccine, and 21 (24.7%) had HIV infection. Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/ mL within 12 weeks after the second dose of vaccine included HIV infection (adjusted odds ratio [aOR], 0.14;95% CI, 0.04-0.51), active hematologic disease (aOR, 5.50;95% CI 1.42-21.32), receipt of anti-CD20 monoclonal antibodies (aOR, 6.65;95% CI 1.52-29.07), and receipt of two doses of homologous mRNA vaccination (aOR, 0.17;95% CI 0.05-0.56). In the participants having previously treated with anti-CD20 regimen, only 8.6% achieved an antibody response ( >141 BAU/mL) in the first year, while 78.3% achieved anti-spike IgG titer > 141 BAU/mL after two years post B-cell depleting treatment. After the third dose of SARS-CoV-2 vaccine, 53.6% achieved an antispike IgG titer > 141 BAU/mL in the first year post anti-CD20 treatment. Conclusion(s): Our study demonstrated that previous treatment with anti-CD20 monoclonal antibodies was associated a lower antibody response among patients with lymphoproliferative disorders receiving two doses of SARS-CoV-2 vaccine. While two doses of SARS-CoV-2 vaccines might not be sufficient even one year apart from the last dose of rituximab, a third dose of vaccine may boost anti-spike IgG particularly in the subset of recent exposure to rituximab. Anti-spike IgG determined 1-3 months after the second (A) / third (B) dose of COVID-19 vaccine, stratified by the interval between last anti-CD20 regimen and the second / third dose of COVID-19 vaccine. (Figure Presented).
ABSTRACT
Disulfiram is an FDA-approved drug that has been used to treat alcoholism and has demonstrated a wide range of anti-cancer, anti-bacterial, and anti-viral effects. In the global COVID-19 pandemic, there is an urgent need for effective therapeutics and vaccine development. According to recent studies, disulfiram can act as a potent SARS-CoV-2 replication inhibitor by targeting multiple SARS-CoV-2 non-structural proteins to inhibit viral polyprotein cleavage and RNA replication. Currently, disulfiram is under evaluation in phase II clinical trials to treat COVID-19. With more and more variants of the SARS-CoV-2 worldwide, it becomes critical to know whether disulfiram can also inhibit viral entry into host cells for various variants and replication inhibition. Here, molecular and cellular biology assays demonstrated that disulfiram could interrupt viral spike protein binding with its receptor ACE2. By using the viral pseudo-particles (Vpps) of SARS-CoV-2, disulfiram also showed the potent activity to block viral entry in a cell-based assay against Vpps of different SARS-CoV-2 variants. We further established a live virus model system to support the anti-viral entry activity of disulfiram with the SARS-CoV-2 virus. Molecular docking revealed how disulfiram hindered the binding between the ACE2 and wild-type or mutated spike proteins. Thus, our results indicate that disulfiram has the capability to block viral entry activity of different SARS-CoV-2 variants. Together with its known anti-replication of SARS-CoV-2, disulfiram may serve as an effective therapy against different SARS-CoV-2 variants.
ABSTRACT
Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.