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Non-Drug Intervention (NDI) is one of the important means to prevent and control the outbreak of coronavirus disease 2019 (COVID-19), and the implementation of this series of measures plays a key role in the development of the epidemic. The purpose of this paper is to study the impact of different mitigation measures on the situation of the COVID 19, and effectively respond to the prevention and control situation in the "post-epidemic era". The present work is based on the Susceptible-Exposed-Infectious-Remove-Susceptible (SEIRS) Model, and adapted the agent-based model (ABM) to construct the epidemic prevention and control model framework to simulate the COVID-19 epidemic from three aspects: social distance, personal protection, and bed resources. The experiment results show that the above NDI are effective mitigation measures for epidemic prevention and control, and can play a positive role in the recurrence of COVID-19, but a single measure cannot prevent the recurrence of infection peaks and curb the spread of the epidemic;When social distance and personal protection rules are out of control, bed resources will become an important guarantee for epidemic prevention and control. Although the spread of the epidemic cannot be curbed, it can slow down the recurrence of the peak of the epidemic;When people abide by social distance and personal protection rules, the pressure on bed resources will be eased. At the same time, under the interaction of the three measures, not only the death toll can be reduced, but the spread of the epidemic can also be effectively curbed. © 2022 ACM.
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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).
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Background: Patients with Inflammatory bowel disease (IBD) receiving anti-TNF or JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the currently dominant Omicron BA.4/5 variants. Method(s): We prospectively recruited 329 adults (68 healthy controls (HC) and 261 IBD) who had received three doses of COVID-19 vaccine at nine UK centres. The IBD population was established (>12 weeks therapy) on either thiopurine (n=60), infliximab (IFX) (n=43), thiopurine and IFX combination (n=46), ustekinumab (n=43), vedolizumab (n=46) or tofacitinib (n=23). Pseudoneutralisation assays were performed and the half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARSCoV-2 neutralising response against wild-type (WT) virus and the BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, ethnicity, vaccine type and age. Result(s): Heterologous (two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both WT SARS-CoV-2 virus and the BA.4/5 variants in HCs and IBD (fig 1). Antibody titres against BA.4/5 were significantly lower than antibodies against WT virus in both groups (Geometric Mean Ratio (GMR) [95% CI], 0.11 [0.09, 0.15], P<0.0001 in healthy participants;GMR 0.07 [0.06, 0.08], P<0.0001 in IBD patients). Multivariable models showed that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in IBD patients on IFX (GMR 0.44 [0.20, 0.97], P=0.042), IFX and thiopurine combination (GMR 0.34 [0.15, 0.77], P=0.0098) or tofacitinib (GMR 0.37 [0.15, 0.92], P=0.032), but not in patients on thiopurine monotherapy, ustekinumab or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against WT and BA.4/5 (P<0.05). Conclusion(s): A third dose of COVID-19 vaccine based on the WT spike glycoprotein boosts neutralising antibody titres in patients with IBD. However, responses are lower against the currently dominant variant BA.4/5, particularly in patients taking anti-TNF or JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed IBD patients may receive additional benefit from bivalent vaccine boosters which target Omicron variants. .
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The Bohai Bay as a typical semi-enclosed bay in northern China with poor water exchange capacity and significant coastal urbanization, is greatly influenced by land-based inputs and human activities. As a class of pseudo-persistent organic pollutants, the spatial and temporal distribution of Pharmaceuticals and Personal Care Products (PPCPs) is particularly important to the ecological environment, and it will be imperfect to assess the ecological risk of PPCPs for the lack of systematic investigation of their distribution in different season. 14 typical PPCPs were selected to analyze the spatial and temporal distribution in the Bohai Bay by combining online solid-phase extraction (SPE) and HPLC-MS/MS techniques in this study, and their ecological risks to aquatic organisms were assessed by risk quotients (RQs) and concentration addition (CA) model. It was found that PPCPs widely presented in the Bohai Bay with significant differences of spatial and seasonal distribution. The concentrations of ∑PPCPs were higher in autumn than in summer. The distribution of individual pollutants also showed significant seasonal differences. The high values were mainly distributed in estuaries and near-shore outfalls. Mariculture activities in the northern part of the Bohai Bay made a greater contribution to the input of PPCPs. Caffeine, florfenicol, enrofloxacin and norfloxacin were the main pollutants in the Bohai Bay, with detection frequencies exceeding 80 %. The ecological risk of PPCPs to algae was significantly higher than that to invertebrates and fish. CA model indicated that the potential mixture risk of total PPCPs was not negligible, with 34 % and 88 % of stations having mixture risk in summer and autumn, respectively. The temporary stagnation of productive life caused by Covid-19 weakened the input of PPCPs to the Bohai Bay, reducing the cumulative effects of the pollutants. This study was the first full-coverage investigation of PPCPs in the Bohai Bay for different seasons, providing an important basis for the ecological risk assessment and pollution prevention of PPCPs in the bay. © 2022 Elsevier B.V.
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The outbreak of COVID-19 has led to the increase in face mask waste globally. In this study, face mask-derived carbocatalysts doped with nitrogen (N-Mask) were fabricated through one-step pyrolysis of 1:5 w/w mixture of face mask and urea at different temperatures to activate peroxymonosulfate (PMS) for gatifloxacin (GAT) degradation. The N-Mask prepared at 800 degrees C (N-Mask800) exhibited the highest GAT degradation rate with k(app) = 0.093 min(-1) which could be attributed to its high N doping level (17.1 wt%) and highest specific surface area (237.13 m(2) g(-1)). The relationship between k(app), catalyst loading and PMS dosage at various pHs on GAT degradation were successfully established. It was also found that the GAT degradation rate was inhibited in the sequential operating mode compared to the simultaneous operating mode. It was construed that adsorption and catalysis share the same active sites. Deterioration in catalytic performance was observed over successive cycles due to the surface chemistry change during catalysis, and difficulty in catalyst recovery after treatment. Radical scavenger study revealed that both radical and nonradical pathways were involved during GAT degradation, with nonradical pathway playing a dominant role. XPS analysis revealed that pyrrolic N and graphitic N can facilitate PMS activation via radical and nonradical pathways. Based on the LC-MS/MS analysis, the GAT degradation intermediates were identified, and the possible degradation pathways were tentatively proposed. Overall, this study demonstrated that carbocatalyst derived from face mask could be transformed into costeffective and environmentally friendly PMS activator for environmental wastewater treatment applications.
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Background: To contain the coronavirus disease 2019 (Covid-19) pandemic, non-pharmacologic interventions, including lockdown and social distancing, may have adverse impact on access to HIV testing and care. This study investigated the impact of Covid-19 on HIV testing and care at a major hospital in Taiwan in 2020-2021. Method(s): The numbers of clients seeking anonymous HIV voluntary counseling and testing were compared 2 years before (2018-2019) and 2 years after Covid-19 outbreak (2020-2021). People living with HIV (PLWH) who sought care at the hospital during 2018-2021 were included to examine the status of HIV care delivery and disposition. Result(s): The annual number of HIV screening tests performed had significantly decreased from 2507 to 2794 in 2018 and 2019, respectively, to 2161 and 1737 in 2020 and 2021, respectively. The rate of discontinuation of HIV care among PLWH was 3.7% in 2019, which remained unchanged in 2020 (3.7%) and 2021 (3.8%). The respective percentage of annual plasma HIV RNA testing <2 times increased from 8.4% to 7.8% in 2018 and 2019 to 7.0% and 10.7% in 2020 and 2021, so was that of annual syphilis testing <2 times (10.1% and 8.8%-7.9% and 12.0%). The rates of plasma HIV RNA <200 copies/ml ranged from 97.0% to 98.1% in 2018-2021. Conclusion(s): During the Covid-19 pandemic, access to HIV counseling and testing was significantly limited. While the number of HIV-related testing decreased, the impact of Covid-19 on the continuity of antiretroviral therapy and viral suppression among PLWH appeared to be minimal in Taiwan. Copyright © 2022
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Objective: To understand the characteristics and associated factors of viral nucleic acid conversion in children infected with Omicron variant strain of SARS-CoV-2 in Shanghai. Methods: The clinical symptoms, laboratory results and other data of 177 children infected with SARS-CoV-2 who were hospitalized in Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University (designated hospital for SARS-CoV-2 infection in Shanghai) from April 25 to June 8, 2022 were retrospectively analyzed. According to the chest imaging findings, the children were divided into mild and common type groups. According to their age, the unvaccinated children were divided into<3 years old group and 3-<18 years old group. According to the vaccination status, the children aged 3-<18 year were divided into non-vaccination group, 1-dose vaccination group and 2-dose vaccination group. Comparison between groups was performed by independent sample t-test and analysis of variance, and multivariate linear regression analysis was used for multivariate analysis. Results: Among the 177 children infected with Omicron variant of SARS-CoV-2, 96 were males and 81 were females, aged 3 (1, 6) years. The time of viral nucleic acid negative conversion was (10.3±3.1) days. The 177 children were 138 cases of mild type and 39 cases of common type. Among the children aged 3-<18 years old, 55 cases were not vaccinated, 5 cases received 1-dose and 36 cases received 2-dose vaccination. Among the 36 children who received 2 doses of vaccination, the time of viral nucleic acid negative conversion was shorter in those vaccinated within 6 months than those over 6 months ((7.1±1.9) vs. (10.8±3.0) d, t=-3.23, P=0.004). Univariate analysis showed that the time of nucleic acid negative conversion of SARS-CoV-2 was associated with age, underlying diseases, gastrointestinal symptoms, white blood cell count, proportion of neutrophils, proportion of lymphocytes, and the number of doses of SARS-CoV-2 vaccine (t=3.87, 2.55, 2.04, 4.24, 3.51, 2.92, F=16.27, all P<0.05). Multiple linear regression analysis showed that older age (ß=-0.33, 95% CI -0.485--0.182, P<0.001) and more doses of vaccination (ß=-0.79, 95% CI -1.463--0.120, P=0.021) were associated with shortened nucleic acid negative conversion time in children, while lower lymphocyte proportion (ß=-0.02, 95% CI -0.044--0.002, P=0.031) and underlying diseases (ß=1.52, 95% CI 0.363-2.672, P=0.010) were associated with prolonged nucleic acid negative conversion time in children. Conclusion: The children infected with Omicron variant of SARS-CoV-2 with reduced lymphocyte proportion and underlying diseases may have longer time of viral nucleic acid negative conversion,while children with older age and more doses of vaccination may have shorter time of viral nucleic acid negative conversion.
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COVID-19 , Nucleic Acids , Child , Female , Male , Humans , Child, Preschool , Adolescent , SARS-CoV-2 , COVID-19 Vaccines , Retrospective Studies , China/epidemiology , Translocation, Genetic , Hospitals, PediatricABSTRACT
SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: COVID-19 patients requiring admission to an ICU have a higher risk of invasive pulmonary aspergillosis (IPA) with a reported incidence of 19.6%-33.3%. CASE PRESENTATION: A 63-year-old male presented with progressively worsening dyspnea for one week. He has a past medical history of atrial fibrillation, hypertension, and obesity. He was tested positive for COVID about two weeks prior. He did receive a single dose of Moderna vaccine. Initial chest x-ray(CXR) showed diffuse ground-glass opacities. He was initiated on Remdesivir and decadron, and later received a dose of tocilizumab. He was intubated on hospital day 3 for worsened hypoxemia. Repeat CXR suggested some improvement but a new left lower lobe airspace haziness. He also had new-onset leukocytosis with elevated procalcitonin level. He was started on cefepime for concern of superimposed hospital-acquired pneumonia. A second dose of tocilizumab was administered. No clinical improvement was seen, and additional workups were obtained. Serial CXRs revealed increasing diffuse airspace opacities concerning for ARDS. Tracheal aspirate culture grew coagulase-negative staphylococcus and Aspergillosis Fumigatus. Cefepime was changed to vancomycin, and voriconazole and caspofungin were added. Unfortunately, the patient's respiratory status worsened with increasing ventilation requirement. He also developed septic shock and acute renal failure requiring CVVH. He became even more hypotensive after CVVH initiation, and multiple vasopressors were required to maintain his hemodynamics. Unfortunately, he continued to deteriorate and he also developed profound respiratory acidosis. He died shortly afterwards after family decided to withdraw care. DISCUSSION: In this case, in addition to superimposed bacterial pneumonia, pulmonary aspergillosis likely also contributed to his clinical deterioration. The mechanism by which fungal infections develop in COVID-19 infection is not well-understood. Severe COVID-related immune dysregulation, ARDS, and high-dose steroids use are potential culprits for the increased risk of IPA. Tocilizumab, an IL-6 receptor monoclonal antibody used in patients with severe COVID-19 infection, may also predispose the patient to IPA according to post-marketing data. The mortality rate from current case reports is as high as 64.7%. Diagnosis and treatment in such a scenario remain a challenge. Sputum culture, serum Beta-galactomannan, Beta-D glucan, and aspergillosis PCR have low sensitivity. Tissue biopsy and CT scan in critically ill patients are often not feasible. Voriconazole is usually considered the first-line treatment in IPA. CYP3A4-mediated drug interactions between azoles and antiviral agents require further investigation. CONCLUSIONS: Clinicians should be aware that severe COVID-19 patients are at higher risk of IPA. The prognosis is poor. Early detection and treatment in clinically deteriorated patients are warranted. Reference #1: Borman, A.M., Palmer, M.D., Fraser, M., Patterson, Z., Mann, C., Oliver, D., Linton, C.J., Gough, M., Brown, P., Dzietczyk, A. and Hedley, M., 2020. COVID-19-associated invasive aspergillosis: data from the UK National Mycology Reference Laboratory. Journal of clinical microbiology, 59(1), pp.e02136-20. Reference #2: Lai CC, Yu WL. COVID-19 associated with pulmonary aspergillosis: A literature review. J Microbiol Immunol Infect. 2021;54(1):46-53. doi:10.1016/j.jmii.2020.09.004 Reference #3: Thompson Iii GR, Cornely OA, Pappas PG, et al. Invasive Aspergillosis as an Under-recognized Superinfection in COVID-19. Open Forum Infect Dis. 2020;7(7):ofaa242. Published 2020 Jun 19. doi:10.1093/ofid/ofaa242 DISCLOSURES: No relevant relationships by Jason Chang No relevant relationships by Jason Chang No relevant relationships by kaiqing Lin No relevant relationships by Guangchen Zou
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Leisure farm tourism would not only allow tourists to experience agricultural activities but also can increase farmers' income and deeply root rural culture. However, during the recent period of COVID-19 leisure farm should consider and evaluate its competitive ability for attracting tourists to go to leisure farm again. In this research LTOPSIS and SWOT technology is applied to evaluate and analyze competitive ability for leisure farms. According to quasi-experimental analysis, case leisure farm should be operated its business carefully due to uncertainty of COVID-19. Leisure farm should retain some fund to avoid the possibility of collapse in the future. © 2022 ACM.
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Eight to ten percent of total global greenhouse gas emissions are associated with food loss and waste. Tackling the challenges of food loss and sustainable food waste management is key to fulfilling the Paris Agreement. However, among the Nationally Determined Contributions to the Paris Agreement, very few countries make references to food loss and waste. In this work, we reviewed the problem of food loss and waste from a global viewpoint and highlighted the opportunities of managing food loss and waste towards carbon mitigation and beyond. The importance of developing a coherent collaboration among all associated stakeholders was implied. Some recent policy developments and the impacts of COVID-19 pandemic are discussed followed by the summarization of potential solutions to tackling the fool loss and waste challenge.
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The authors reported the clinical course of a 58-year-old female suffering from cerebral venous sinus thrombosis associated with hemorrhage after the ChAdOx1 nCov-19 vaccination. Emergent decompressive craniectomy was performed, and aggressive blood transfusion was given. Nevertheless, progressive intracerebral hemorrhage and thrombocytopenia developed. A delayed diagnosis was made on a rare complication of vaccine-induced immune thrombotic thrombocytopenia (VITT) with a positive result of anti-platelet factor 4 antibodies (PF4 Ab). The patient died 4 days postoperative due to brainstem failure.
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Background: Symptoms reduction is a crucial outcome to be considered when testing novel treatments for COVID-19. The goal was to assess the impact of casirivimab+imdevimab (cas+imd) dose/exposure on the trajectory and resolution time of symptoms in outpatients with COVID-19. Methods: Analysis used data from the COV-2067 trial (NCT04425629). Cas+imd was administered intravenously (total dose 1.2 to 8 g). Symptoms data were collected using SE-C19, a patient-reported survey developed de novo to assess the symptomatic course of COVID-19. Based on patients' responses on SE-C19, a Rasch analysis was used to derive a latent score to infer their overall underlying symptom severity. A direct response model was fitted to the latent score-time data to quantify the effects of dose/exposure, demographic and clinical characteristics on latent symptom trajectory. Symptoms resolution time was defined as time from randomization to the 1st day during which the patient scored "no symptom". Several parametric models were tested as structural model, assuming a known distribution, eg, exponential or Weibull, for time to symptoms resolution data. Risk variables (eg, binary treatment or categorical dose levels, exposure metrics, baseline demographic, clinical, and biological characteristics) were tested as covariates using a proportional hazard model. Results: Results from the direct response model suggest that each dose, as compared to placebo, remarkably reduced IT50 (time taken to achieve half of the maximal response of reducing symptom) by ∼40%. By excluding data from placebo arm, none of the tested doses or predicted exposures, were significant covariates on any of the model parameters. Results from the parametric regression analysis further confirmed that cas+imd (HR=1.25) is a major factor shortening the symptoms resolution time in a dose-and exposure-independent manner. Males (HR=1.13) have a shorter symptoms resolution time. Older age (HR=0.991), higher BMI (HR=0.988), and more severe baseline symptoms (HR=0.783 for moderate and 0.589 for severe) significantly contribute to longer symptoms resolution time. Conclusion: Treatment with cas+imd (1.2 g or above), rapidly resolved symptoms in outpatients in a dose-and exposure-independent manner as indicated by a direct response model using derived latent score and further confirmed by a survival analysis using time to symptoms resolution. In addition, symptom severity, age, BMI, sex were major risk factors affecting the symptoms resolution time.
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Background: A large-scale community COVID-19 outbreak occurred between April and August 2021 in Taiwan, where non-pharmaceutical interventions (NPIs) have been strictly implemented and COVID-19 vaccination program was not implemented until 1 March, 2021. Although COVID-19 vaccination is recommended for at-risk populations, the vaccine effectiveness in people living with HIV (PLWH) remains incompletely understood. We evaluated the effectiveness of COVID-19 vaccination among PLWH during a COVID-19 outbreak in Taiwan. Methods: From 1 March to 30 September, 2021, all adult PLWH without previous SARS-CoV-2 infection were included and advised to receive 2 doses of COVID-19 vaccine. The government-funded vaccination campaign provided different types of COVID-19 vaccine, including ChAdOx1 nCoV-19 (AZD1222), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and MVC-COV1901 (Medigen) vaccines. The primary endpoint of this study was the vaccine effectiveness in preventing COVID-19 among PLWH, which was estimated by comparing incidence rates between the unvaccinated, partially vaccinated, and fully vaccinated groups in a dynamic cohort. Results: During the study period, 3131 PLWH were included, with 99.9% on antiretroviral therapy, 99.8% being MSM and median CD4 count of 627 cells/mm3. In the dynamic cohort, 3128 PLWH contributed 516892 person-days of follow-up (PDFU) to the unvaccinated group, 2476 PLWH contributed 139163 PDFU to the partially vaccinated group, and 236 PLWH contributed 12011 PDFU to the fully vaccinated group (Table). During the follow-up, 37 PLWH (1.2%) acquired SARS-CoV-2 infections. The incidence rate of SARS-CoV-2 infection was 6.4 per 100,000 PDFU in the unvaccinated group, which decreased to 2.9 and 0 per 100,000 PDFU in the partially and fully vaccinated groups, respectively. The adjusted incidence rate ratios were 0.47 (95% CI, 0.17-1.32) in the partially vaccinated group and <0.01 in the fully vaccinated group compared with the unvaccinated group, resulting in vaccine effectiveness rates of 53.4% and 99.9% for single-and 2-dose COVID-19 vaccination, respectively. Conclusion: COVID-19 vaccination was clinically effective among PLWH during the outbreak setting where NPIs were strictly implemented.
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Background: Casirivimab+imdevimab (hereinafter referred to as drug) remains vital in reducing hospitalization/death by 70% when administered early in the course of the infection. Our aim was to illustrate the mechanism of drug action in vivo and determine the magnitude of antiviral efficacy of various dose regimens given to outpatients with COVID-19, evaluating the presence of SARS-CoV-2 sero-antibody and ≥1 high-risk factor for developing severe COVID-19 illness as predictors of viral kinetics. Methods: Analysis data came from 2 clinical studies in SARS-CoV-2 infected outpatients with no or ≥1 risk factor for severe COVID-19 (NCT04425629 and NCT04666441), who received single dose of placebo or drug IV (300mg to 8g) or SC (600mg to 1.2g), had assessed viral load in nasopharyngeal swab and drug concentrations in serum (N=4500). The median number of viral load assessments per patient was 5 (range 1-8) within up to 14 days of follow-up time. Drug concentrations were predicted using the individual pharmacokinetic parameters yielded by a population model. The median patient age was 42 years, with similar proportion of males and females. The median viral load at baseline was 6.79 log10 copies/mL, and the median time of symptom onset was 3 days before study baseline. A standard target cell-limited model was used to estimate the time of infection and reconstruct viral kinetic profiles. Various relationships between exposure and resulting antiviral response were evaluated, where the drug could block de novo infection, increase the elimination rate of infected cells, or reduce viral production from infected cells. Results: The results support that the main mechanism of drug action is blocking de novo infection with an estimated decrease in the infectivity rate of 96.6%, for all dose regimens evaluated herein. High-risk factor for severe COVID-19 and baseline sero-antibody-positive/other status were associated with a 4.71% decrease and a 4.96% increase in the elimination rate of infected cells, respectively. The estimated median and 95th percentile of time to viral clearance (ie, viral count reaches below assay quantification limit) were 1.4 and 3.4 days shorter in drug vs placebo (median 10.6 vs 12.0 days, and 95th percentile 15.2 vs 18.6 days). Conclusion: All IV and SC casirivimab+imdevimab dose regimens evaluated herein showed similar near-maximal antiviral activity by blocking de novo infection;hence, shortening the time to virus clearance.
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Background: Antibody responses following SARS-CoV-2 infection or a single-dose of SARS-CoV-2 vaccine are impaired in patients with inflammatory bowel disease treated with anti-TNF compared to those treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody. Here we sought to determine if patients treated with infliximab have attenuated serological and T cell responses and an increased risk of breakthrough COVID-19 infection following primary SARS-CoV-2 vaccination. Methods: Anti-spike (S) receptor binding domain (RBD) antibody concentration in 2306 infliximab-treated patients were compared to a cohort of 1045 vedolizumab-treated patients. Our primary outcome was anti-S RBD antibodies 2 to 10 weeks after a second dose of the BNT162b2 or ChAdOx1 nCoV-19 vaccines. Secondary outcomes were anti-spike T cell responses, durability of vaccine responses and risk of breakthrough infections following two doses of vaccine. Results: Anti-S RBD antibody concentrations were lower in patients treated with infliximab than in those treated with vedolizumab, following a second dose of BNT162b2 (567.3 U/mL [6.1] vs 4601.1 U/ mL [5.3], p <0.0001) and ChAdOx1 nCoV-19 (183.9 U/mL [5.0] vs 789.4 U/mL [3.5], p <0.0001) vaccines (Fig. 1). Vaccination with the BNT162b2 vaccine compared to the ChAdOx1 nCoV-19 was independently associated with a 3.7-fold [95% CI 3.30 - 4.13] higher anti-S RBD antibody concentration (p < 0.0001) (Fig. 2). There were no significant differences in the magnitude of anti-spike T cell responses observed in infliximab- compared with vedolizumabtreated patients after one or two doses of either vaccine. Antibody half-life was shorter in infliximab- than vedolizumabtreated patients following two-doses of BNT162b2 (4.0 weeks [95% CI 3.8 - 4.1] vs 7.2 weeks [95% CI 6.8 - 7.6]) and ChAdOx1 nCoV- 19 (5.3 weeks [95% CI 5.1 - 5.5] vs 9.3 weeks [95% CI 8.5 - 10.2], p value < 0.0001). Breakthrough SARS-CoV-2 infections were more frequent (5.8% (202/3467) vs 3.9% (66/1691), p = 0.0032) and the time to breakthrough shorter in patients treated with infliximab than vedolizumab (p = 0.0023) (Fig. 3). Higher anti-S RBD antibody concentrations following a second dose of SARS-CoV-2 vaccine protected against breakthrough SARS-CoV-2 infection: overall, for every 10-fold rise in anti-S RBD antibody level we observed a 0.8-fold reduction in odds of breakthrough infection ([95% CI 0.70 - 0.99], p = 0.035). Conclusion: Infliximab was associated with attenuated, less durable vaccine induced anti-S RBD antibody responses and a 50% increase in breakthrough SARS-CoV-2 infection. Further follow-up is required to assess whether third primary doses can mitigate the effects of infliximab on anti-S RBD antibody responses.