ABSTRACT
Background: COVID-19 pandemic still pose a substantial threat worldwide despite increasing vaccine availability. Patients with haematological malignancies have been shown to have increased risk of contracting COVID-19 and are more susceptible to develop severe illness from SARS-CoV- 2 infection. The immune response to vaccines is impaired in patients with haematological malignancy due to underlying disease or antineoplastic therapies. The monoclonal-antibody combination, Evusheld is composed of tixagevimab and cilgavimab, two neutralising antibodies against SARS-CoV- 2. It has been shown to be safe and have efficacy for the prevention of COVID-19. Our aim of study is to describe the incidence and outcome of breakthrough COVID-19 infection among patients who received Evusheld in our centre and analyse the factors that possibly increase the risk of breakthrough infection. Material(s) and Method(s): A retrospective review of all adult patients with haematological malignancy who received tixagevimab/ cilgavimab 150/150 mg injection in Hospital Pulau Pinang from 1 July 2022 to 31 August 2022 with a follow-up period to 30 November 2022 was conducted. Demographic data, clinical characteristics and outcome will be retrieved from patient's medical records. Data were analysed using Statistical Package for Social Sciences software (version 21.0). Result(s): A total of 96 patients (50 males and 46 females) received tixagevimab/cilgavimab injection during the study period with a median age of 61 years (range 19-82). Majority of them were diagnosed with multiple myeloma (42.7%), followed by lymphoma (33.3%) and leukaemia (24%). One third of them had history of therapy with monoclonal antibody and 20% had haematopoietic stem cell transplantation. No major adverse effects of tixagevimab/cilgavimab injection were noted among the study population. Of the 12 patients (12.5%) who had COVID-19 infection, all of them had mild infection;three were asymptomatic and six patients received Paxlovid antiviral therapy. The median time from tixagevimab/cilgavimab to the onset of COVID-19 infection was 35 days (range 5-97 days). The mean age of patients with breakthrough COVID-19 infection were older compared to those without breakthrough infection but was not statistically significant. The incidence of breakthrough COVID-19 infection was not affected by type of haematological malignancy, history of monoclonal antibody therapy or COVID-19 vaccination. Discussion and Conclusion(s): Our findings showed that tixagevimab/cilgavimab was safe and effective in preventing COVID-19- related morbidity and mortality among patients with haematological malignancy during the study period. However, the limitation is the lack of access to whole genome sequencing for detection of resistant variants for breakthrough infections.
ABSTRACT
Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs). Objective(s): to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19. Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 +/- 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up. Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by aseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 +/- 3.2 days versus 4.6 +/- 1.6 days in group 1, p < 0.001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.Copyright © 2023 Russian Transplant Society. All rights reserved.
ABSTRACT
Background/Aims The immune response to SARS-CoV-2 is known to be reduced in the immunocompromised. However, extent to which immunity is affected by immunosuppression in specific disease cohorts remains poorly characterised. Furthermore, implications of the ongoing vaccination booster programme require further study. Individuals with lupus nephritis (LN) require prolonged high-dose immunosuppression in order to maintain disease control, rendering them important to study in this context. We evaluated SARS-CoV-2 nucleocapsid and spike antibody response in this cohort during the Spring/Summer 2022 booster vaccine campaign. Nucleocapsid antibody indicates previous infection whilst spike antibody indicates previous infection and/or vaccination response. Titre of spike antibody to prevent infection is not known, but presence of antibodies is likely to protect against severe disease. Methods SARS-CoV-2 spike and nucleocapsid antibody were measured in adult patients with LN attending a tertiary centre rheumatology clinic. Data was collected retrospectively on disease, immunosuppression, vaccine status and history of natural exposure. Results 35 cases of LN were investigated, of which LN III, IV and V were predominant biopsy diagnoses. Regarding immunosuppressants, the Eurolupus Cyclophosphamide protocol had been used in the majority of patients to achieve initial control, with 3/35 patients still receiving pulsed courses at data collection. 18/35 were on Mycophenolate Mofetil;a further 13/35 had previously received this. 31/35 took at least 5mg Prednisolone daily;25/35 took Hydroxychloroquine;7/35 took Azathioprine;7/35 had previously been on Methotrexate, 3/35 took Tacrolimus;1/35 took Ciclosporin. Regarding B-cell depleting monoclonal antibody therapy, 13/35 had received Rituximab and 8/35 were receiving Belimumab. Antibody levels were measured between 4 weeks and 13 months after last dose of vaccination;mean duration was 6 months. 11/35 had confirmed COVID-19 infection;a further 8/35 reported a possible history. Of the 35, 32 (91%) had mounted detectable SARS-CoV-2 spike antibody above the bottom 10% of assay detection, indicating some immunity to vaccination or natural exposure. 20 (57%) had detectable nucleocapsid antibody, suggesting natural infection with antibody response. Only 2 (6%) had not mounted any antibody response. Of note, neither were fully vaccinated: one had 1 vaccination with blood test 8 months subsequent;one had 2 vaccinations with blood test 7 months subsequent. The latter was also notably on haemodialysis. All who received 3+ vaccinations had detectable spike antibody responses, as well as 75% of those who had received 2 vaccinations. Conclusion Our study is the first analysis, to our knowledge, of SARS-CoV-2 antibody response in a LN cohort. Whilst neutralising capacity and level of antibody providing protection remains under research, these findings provide at least some reassurance that individuals with LN on immunosuppression are capable of mounting an immune response against SARS-CoV-2. Further work is required to establish extent and duration of protection with serial vaccinations in this cohort.
ABSTRACT
BACKGROUND: Monoclonal antibody (MAB) treatments for COVID-19 received Emergency Use Authorization in the United States. METHODS: We used surveillance data from Rhode Island to conduct a retrospective, statewide cohort study to estimate the effectiveness of MABs for preventing hospitalization and death during periods when Alpha and Delta variants were predominant. RESULTS: From 1/17/2021-10/26/2021, 285 long-term congregate care (LTCC) residents and 3,113 non-congregate patients met our eligibility criteria and received MAB; they were matched to 285 and 6,226 controls, respectively. Among LTCC residents, 8.8% (25/285) of patients who received MAB were hospitalized or died compared to 25.3% (72/285) of those who did not receive MAB (adjusted difference=16.7%, 95% confidence interval CI=11.0-22.3%). Among non-congregate patients, 4.5% (140/3,113) of patients who received MAB were hospitalized or died compared to 11.8% (737/6,226) of those who did not receive MAB (adjusted difference=7.2%, 95% CI=6.0-8.4%). CONCLUSIONS: Administration of MABs led to an absolute reduction in hospitalization or death during periods when Alpha and Delta variants were predominant.
Subject(s)
COVID-19 , Humans , Cohort Studies , Retrospective Studies , SARS-CoV-2 , Hospitalization , Antibodies, Monoclonal/therapeutic useABSTRACT
Purpose of study The COVID-19 pandemic led to an unprecedented rapid transmission of healthcare information. This information was critical to enact frequently changing patient care protocols and to inform staff about redistribution of hospital resources at New York University Langone Hospital- Long Island. In this investigation, we analyze our hospital clinicians' methods of mass communication to front-line health care workers, with particular interest in assessing how communication was informed by real-time clinical findings. At the height of the pandemic (March 25th- April 15th), a mass broadcast email disseminated daily from the Director of Pulmonary and Critical Care was effective in informing treatment protocols that were clinically observed to improve patient outcomes. We analyzed over thirty broadcast emails and identified three major categories of information that were routinely addressed and/or updated: (i) reallocation of resources, (ii) clinical protocol changes, (iii) recommended lab tests for monitoring patient clinical course. We also interviewed key hospital clinicians and administrators on their experience working during the height of the pandemic. We found treatment protocols in these emails included information regarding the use of steroids and monoclonal antibody therapy, ventilators, and patient repositioning. In addition, the hospital's first autopsy results on COVID related deaths gave further insight into the disease process and manner of death for many patients (diffuse alveolar damage and evidence of hypercoagulability). So, too, did clinical findings around this time support what was seen grossly on autopsy-patients with more severe disease often presented with serial d-dimer levels >6x the normal limit. The information through these different conduits was synthesized and subsequently communicated in the aforementioned mass emails as an anticoagulation treatment protocol. Through continuous input of data, this protocol was updated and adjusted over the course of three weeks. We found that real-time communication amongst hospital staff regarding patient treatment protocols was a dynamic process that required synthesis of lab values, autopsy findings, and observed response to treatments. Successful treatment of patients depended on continuous review and communication of this information. Methods used The COVID-19 pandemic led to an unprecedented rapid transmission of healthcare information. This information was critical to enact frequently changing patient care protocols and to inform staff about redistribution of hospital resources at New York University Langone Hospital-- Long Island. In this investigation, we analyze our hospital clinicians' methods of mass communication to front-line health care workers, with particular interest in assessing how communication was informed by real-time clinical findings. At the height of the pandemic (March 25th- April 15th), a mass broadcast email disseminated daily from the Director of Pulmonary and Critical Care was effective in informing treatment protocols that were clinically observed to improve patient outcomes. Summary of results We analyzed over thirty broadcast emails and identified three major categories of information that were routinely addressed and/or updated: (i) reallocation of resources, (ii) clinical protocol changes, (iii) recommended lab tests for monitoring patient clinical course. We also interviewed key hospital clinicians and administrators on their experience working during the height of the pandemic. We found treatment protocols in these emails included information regarding the use of steroids and monoclonal antibody therapy, ventilators, and patient repositioning. In addition, the hospital's first autopsy results on COVID related deaths gave further insight into the disease process and manner of death for many patients (diffuse alveolar damage and evidence of hypercoagulability). So, too, did clinical findings around this time support what was seen grossly on autopsy- patients with more severe disease often presented with seri l d-dimer levels >6x the normal limit. The information through these different conduits was synthesized and subsequently communicated in the aforementioned mass emails as an anticoagulation treatment protocol. Through continuous input of data, this protocol was updated and adjusted over the course of three weeks. Conclusions We found that real-time communication amongst hospital staff regarding patient treatment protocols was a dynamic process that required synthesis of lab values, autopsy findings, and observed response to treatments. Successful treatment of patients depended on continuous review and communication of this information.
ABSTRACT
Background: Given effectiveness of SARS-CoV-2 vaccines and outpatient antiviral and monoclonal antibody therapy for reducing progression to severe COVID-19, we sought to estimate the impact of these interventions on risk of hospitalization following SARS-CoV-2 infection in a large US healthcare system. Method(s): All patients >=18 of age in the UNC Health system, with first positive SARS-CoV-2 RT-PCR test or U07.1 ICD-10-CM (diagnosis date) during 07/01/2021- 05/31/2022, were included. The outcome was first hospitalization with U07.1 ICD-10-CM primary diagnosis <=14 days after SARS-CoV-2 diagnosis date. SARS-CoV-2 vaccinations were included if received >=14 days prior to diagnosis. Outpatient therapies were included if administered after diagnosis date and before hospital admission. Age, gender, race, ethnicity, and comorbidities associated with COVID-19 (using ICD-10-CM, if documented >=14 days prior to diagnosis date) were also evaluated. Risk ratios for hospitalization were estimated using generalized linear models, and predictors identified using extreme gradient boosting using feature influence with Shapley additive explanations algorithm. Result(s): The study population included 54,886 patients, 41% men and 27% >=60 years of age. One-third of SARS-CoV-2 diagnoses occurred July-December 2021 and 67% December-May 2022 (predominantly Delta and Omicron variants, respectively). Overall 7.0% of patients were hospitalized for COVID-19, with median hospitalization stay of 5 days (IQR: 3-9). 32% and 12% of patients received >=1 SARS-CoV-2 vaccine dose and outpatient therapy, respectively. Unadjusted and age-adjusted hospitalization risk decreased with vaccination and outpatient therapy (TABLE). Comparing patients who received 3 vaccine doses versus none we observed a 66% relative reduction in risk, with stronger association for more recent vaccination. For patients who received nirmatrelvir/ ritonavir versus no therapy we observed a 99% relative reduction in risk. In predictive models, older age was the most influential predictor of being hospitalized with COVID-19, while vaccination and outpatient therapy were the most influential factors predicting non-hospitalization. Conclusion(s): The impact of recent SARS-CoV-2 vaccination and outpatient antiviral and monoclonal antibody therapy on reducing COVID-19 hospitalization risk was striking in this large healthcare system covering Delta and Omicron variant timeframes. SARS-CoV-2 vaccinations and outpatient therapeutics are critical for preventing severe COVID-19. Unadjusted and age-adjusted risk ratios for hospitalization among patients with SARS-CoV-2.
ABSTRACT
The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of a number of basic anti-inflammatory drugs (DMARDs) and biological DMARDs on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biological DMARDs and to search for alternative therapy programs to maintain control over disease activity. Purpose of the study - to evaluate the efficacy and safety of the drug Artlegia (olokizumab), solution for subcutaneous injection, 160 mg/ml - 0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheumatoid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic. Materials and methods. The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000-500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. At 4, 8, 12 weeks after the switch, the severity of pain was assessed on the VAS scale, the number of painful and swollen joints (TJC28 and TSC28), the level of acute phase markers of inflammation, the DAS28 disease activity index calculated using ESR and CRP, and the CDAI (clinical activity index), functional state index HAQ, as well as assessment of the safety profile of therapy. Results. Data analysis was performed using median values (Me) were used for data analysis. A significant decrease of TJC28 was after the injection of olokizumab (Artlegia) in 8 and 12 weeks (Me baseline = 10;Me 8 weeks = 4;Me 12 weeks = 4;p<0.05) and a decrease of TSC28 in 4, 8 and 12 weeks (Me baseline = 9;Me 4 weeks = 3.5;Me 8 weeks = 2.5;Me 12 weeks = 2.0;p<0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me baseline = 21, Me 4 weeks = 1 (p<0.05);ESR: Me baseline = 31, Me 4 weeks = 7 (p<0.05)). Positive dynamics persisted at 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0;ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by the fourth week 4 became within the normal range, regardless of the initial values. All activity indices improved from the fourth week in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22 (p<0.05);DAS28-CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45 (p<0.05);CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0 (p<0.05). All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by the 12th week of the study: Me baseline = 1.62, Me 12 weeks = 1.31 (p<0.05). Conclusion. The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
ABSTRACT
Objectives: To describe the implementation of an ED-based program to offer monoclonal antibody therapy to patients with mild-moderate COVID-19 disease. Background(s): Monoclonal antibody therapy (MOAB) has recently emerged as a treatment for mild to moderate COVID-19, potentially preventing those with underlying conditions from progressing to severe illness and hospitalization. Further, as EDs are the primary point of health care access for many at-risk individuals, offering MOAB in the ED may increase availability of treatment options for patients from traditionally underserved communities. Method(s): A retrospective chart review was conducted of patients 12 years and above who received treatment in our urban, academic, community hospital. Patients 12 years and older were screened for eligibility during ED visits or during follow-up calls providing positive test results. Staff was trained on specific consent, infusion, monitoring, and documentation procedures adherent to MOAB administration under the Emergency Use Authorization. Patients were contacted following MOAB and queried regarding symptom resolution and healthcare utilization. Data regarding patient demographics, ED course, and 7-day unscheduled visits were collected. Result(s): In this ongoing quality improvement initiative, from December 2020 to March 2021, there were 26,229 patient encounters at the pilot ED site. 84 patients were provided MOAB, 87% Bamlanivimab and 13% Bamlanivimab/Etesevimab. Patients had a mean age of 52.3 years (SD 24.4);21% were 12-17 years of age and 37% were >65 years old. 52% were male. 33% self-reported as Caucasian, 19% Black, 18% Asian/Pacific Islander, 21% as other, and 9% were unknown. 17% identified as Latinx. 19% of patients were insured by Medicaid, 36% Medicare, 39% commercially insured, and 6% were uninsured. Patients had symptoms a median of 3 days prior to MOAB. After age (46%), the most commonly reported eligibility criteria was obesity (20%), followed by hypertension (11%) and immunocompromised state (11%). 74% of infusions were administered during nights and weekends. No infusion reactions occurred. 8% returned to an ED within 7 days of MOAB, 5% were hospitalized. No patients required ICU admission or died. Conclusion(s): ED-based MOAB has been safely implemented and may be an effective treatment for patients with mild to moderate COVID-19. Health-system wide expansion of this program may provide opportunities to offer this life-saving therapy to underserved populations with poor access to care.Copyright © 2023
ABSTRACT
As of April 2022, the Mater Hospital serves 190 patients who have been the recipient of a lung transplant in Ireland. During the COVID-19 pandemic, solid organ transplant was recognised as a risk factor for progression to severe disease. In January 2022, the European Medicines Agency (EMA) approved the use of Sotrovimab for high risk patients. Sotrovimab is a monoclonal antibody which neutralises SARS-CoV-2 with recent data showing efficacy in reducing the risk of progression to severe disease in high risk patients . We aim to describe our patient cohort and the rates of COVID-19 infection seen before and after the introduction of monoclonal antibody therapy. While likely reflecting emerging variants resulting in less severe disease, we observe variation in morbidity and mortality in this time. From March 2020 to April 2022, 116 post-lung transplant patients tested positive for COVID-19 infection. This represents 61% of our overall population. Since January 2022, coinciding with the surge of the omicron variant, 57 patients contracted COVID-19. 47 were deemed to be suitable for treatment with 10 presenting outside the window for therapeutic intervention. 3.5% (n=2) required ICU admission and 2 died directly as a result of COVID-19. Prior to this, 58 patients contracted COVID-19, 31 of which (53.5%) required hospital admission with 18 (58%) requiring ICU admission. Overall we saw 13 deaths representing 22.4% of this group and 6.8% of the overall population.
ABSTRACT
During the treatment of critically ill COVID-19 patients it has been revealed that the neutralizing monoclonal antibodies against 2019-nCoV have the advantages of high specificity, high purity, and can be prepared in a large scale, which are expected to be a effective preparation for clinical use. This article introduces the way of 2019-nCoV invasion into the host cells, the major variants of novel coronavirus, and the mechanism of action of anti-2019-nCoV monoclonal antibodies, as well as the progress of research and development of their preparation in major pharmaceutical companies, to provide reference for scientific research and clinical application.Copyright © Chinese Journal of Clinical Infectious Diseases.All rights reserved.
ABSTRACT
The objective was to evaluate real-world effectiveness of sotrovimab, a monoclonal antibody (mAb) for the treatment of high-risk outpatients with COVID-19, in reducing the risk of mortality or hospitalization during the SARS-CoV-2 Delta and initial Omicron variant waves in the US. A retrospective analysis was conducted of de-identified, high-risk patients diagnosed with COVID-19 (index date) from 1 September 2021 to 28 February 2022 in the FAIR Health FH NPIC claims database. Patients were divided into 2 cohorts based on claimed procedural codes: treated with sotrovimab and not treated with any mAb (no mAb). Facility-reported mortality ("mortality"), all cause hospitalizations and intensive care unit (ICU) admissions <=30 days of index were identified. Multivariable logistic regression was conducted to estimate the risk of 30-day mortality or hospitalization, adjusting for demographic and clinical factors. Of the high-risk COVID-19 patients identified,13,140 were treated with sotrovimab and 1,283,284 received no mAb therapy. In the no mAb cohort, 0.59% died and 5.74% were hospitalized (of whom 30% in ICU). In the sotrovimab cohort, 0.08% died and 2.50% were hospitalized (of whom 15% in ICU). After adjusting for potential confounders, sotrovimab treatment was associated with 85% reduced odds of 30-day mortality (OR: 0.15, 95% CI: 0.08-0.31) and 61% reduced odds of 30-day hospitalization or mortality (OR: 0.39, 95% CI: 0.35-0.44) among high-risk COVID-19 patients. In this US real-world study of high-risk COVID-19 patients during the Delta and initial Omicron waves, treatment with sotrovimab was associated with reduced odds of mortality and hospitalization compared to no mAb treatment.
ABSTRACT
BACKGROUND: Monoclonal antibodies represent one option for treatment of COVID-19 early after infection. Although large clinical trials have been successfully conducted, real world data are needed to obtain a realistic assessment of the assumed effect on hospitalization rates. METHODS: For this retrospective, observational study, clinical data were collected in 2021 from outpatients (402) as well as hospitalized patients (350) receiving monoclonal antibodies Bamlanivimab, Casirivimab/Imdevimab or Etesevimab/Bamlanivimab. These data were compared with data from a control group of patients not receiving antibodies because admission to the hospital was too late for this therapy. RESULTS: Both groups showed a comparable spectrum of risk factors. Due to the late hospitalization of control patients, a higher frequency of severe symptoms, such as fever, dyspnea, syncope and lower viral load, were observed. CRP and leukocytes counts were also higher in the untreated group. Most importantly, hospitalization time was significantly shorter and the number of deaths was also lower in the treated group. CONCLUSIONS: Apparently, the application of anti-SARS-CoV-2 antibodies reduced the work load of our hospital as shown by the shorter hospitalization time and lower number of COVID-19-related deaths.
ABSTRACT
The burden of morbidity and mortality from SARS-CoV-2 infection is especially significant in heart transplant patients who are at higher risk for poor outcomes owing to immunosuppression, blunted response to vaccination, and multiple comorbid conditions. Over the last 3 years the therapeutic landscape for COVID-19 has evolved and our drug armamentaria continues to expand. With these advancements comes a time of great hope to mitigate significant illness from SARS - CoV - 2 infection. However, as with many emerging frontiers, the administration of novel therapeutics to a complex patient population remains challenging. We present a patient case encountered at our institution that highlights the need for increased awareness of nuances while managing COVID-19 infection in a heart transplant recipient.
ABSTRACT
Background. Patients receiving CAR-T therapy may have impaired humoral responses to SARS-CoV-2 vaccinations due to their high net state of immunosuppression associated with the underlying disease, prior lines of therapy and CAR-T treatment associated hypogammaglobinemia. Comprehensive data on vaccine immunogenicity in this patient population are currently lacking. Methods. A single-center retrospective study of adults receiving CD19 CAR-T therapy for non-Hodgkin's lymphoma was conducted between 3/27/2018 - 8/31/ 2021. Patients received at least two doses of COVID-19 vaccinations with BNT162b2 (Pfizer, BioNTech), mRNA-1273 (Moderna), or 1 dose of Ad26.COV2.S (Janssen) and had SARS-CoV-2 anti-spike (S) levels measured at least one month after the last vaccine dose. We excluded patients who received COVID-19 monoclonal antibody therapy or immunoglobulin within 3 months of the index anti-S titer. Patients were followed from the time of the first COVID-19 vaccines through their index anti-S antibody result. Patients were censored on the first day of any additional antineoplastic therapy after disease relapse. Our primary endpoint was the percentage of patients who develop a positive anti-S response (assessed by anti-S assay cutoff of >0.8 U/mL, Roche assay). Results. Twenty-five patients met eligibility. Median age was 65 years (range 41 - 78), and majority of patients were male (72%). The number of patients with a positive antibody response was 12 (48%). Median number of vaccines received was 3. 18 patients (72%) received Pfizer vaccines, 4 patients (16%) received Moderna, 2 patients (8%) received Moderna and Pfizer, and 1 patient (4%) received Janssen and Pfizer. Median anti-S titers among patients with a positive response was 111 U/mL (range 2.44 - 12500). Two patients (8%) had COVID-19, both with negative anti-S responses. Conclusion. Our analysis shows that only 48% of patients who received CAR-T therapy developed a positive antibody response after at least two COVID-19 vaccine doses, with a low median titer among responders. This patient population is at higher risk for developing severe COVID-19 disease and likely remains vulnerable even after vaccination. Alternative approaches are needed to prevent COVID-19 and mitigate disease severity in patients undergoing CAR-T.
ABSTRACT
Background. We assessed correlation between prior acceptance of COVID-19 vaccination and acceptance of monoclonal antibody (MAb) treatment for mild-to-moderate COVID-19. Methods. Adult outpatients evaluated for treatment with MAb between August 31st, 2021 and April 23, 2022 in a large tertiary care VA healthcare system were included. MAb therapies administered over the period included casirivimab-imdevimab, sotrovimab, and bebtelovimab. All patients were screened by a small central clinician team with experience discussing COVID therapies under Emergency Use Authorization (EUA). Baseline characteristics, rationale for not offering MAb, and rates of vaccination and acceptance of therapy were recorded. In addition, rates of acceptance for the initial 4 months were compared to rates during the second 4 months of the program, using Chi-square or Fisher's exact test. Results. 203 patients (mean age 68, 91% male) with early COVID-19 were screened for MAb. 68% were vaccinated. 158 (78%) of those screened were offered MAb. The most common reason MAb was not offered was duration of illness longer than specified by EUA (65%). 112 (71%) patients offered MAb accepted, and 94 (84%) received MAb. Of 106 vaccinated patients offered MAb, 81 (76%) accepted. In contrast, of 52 unvaccinated patients offered MAb, only 31 (60%) accepted (Chi-square p = 0.046). However, when analyzed over time, unvaccinated patients were significantly more likely to accept MAb during the second 4 months of the program (7/7 patients, 100%) than during the first 4 months of the program (24/45 patients, 53%, Fisher's exact p = 0.033). This disparity was not seen in vaccinated patients, who accepted MAb at a rate of 73% during the first half of the program, and 88% during the second half (Chi-square p = 0.19). Conclusion. Vaccinated patients were significantly more likely to accept MAb therapy for COVID-19 than unvaccinated patients, suggesting that willingness to accept COVID-19 vaccination predicts willingness to accept other COVID-19 therapeutics. However, disparity in acceptance rates in our population is significantly attenuating over time, suggesting a 'late-adopter,' phenomenon that has implications for continued efforts to encourage therapeutics and vaccines for COVID-19.
ABSTRACT
Background. Effective therapeutic agents for the treatment of COVID-19 have been investigated since the onset of the pandemic. Monoclonal antibodies targeting the spike protein of SARS-CoV-2 have been developed for treatment of mild or moderate COVID disease in high-risk populations. Despite widespread use in the adult population, data are limited on the safety and efficacy of monoclonal antibody infusions in the adolescent and young adult population. Methods. Patients who received bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for treatment of mild COVID disease at Cincinnati Children's Hospital Medical Center from 5/1/2020 through 3/1/2022 were identified retrospectively. In accordance with the FDA EUA, patients were eligible for monoclonal antibody administration if they were >=12 years of age, weighed >=40kg, and were at high risk of progressing to severe disease or hospitalization. Results. Ninety-four patients received monoclonal antibody therapy, of which 14 (13.5%) received either bamlanivimab or bamlanivimab-etesevimab, 54 (51.9%) received casirivimab-imdevimab, and 26 (25%) received sotrovimab. Ten patients (10.6%) experienced one or more adverse events. Of those, 2 (14.3%) received either bamlanivimab or bamlanivimab-etesivimab, 7 (12.9%) received casirivimab-imdevimab, and 1 (3.8%) received sotrovimab. Most common symptoms include rash, nausea, and throat irritation (table R1), the majority (90%) of which were mild, either self-resolving with infusion cessation (60%) or persistent but requiring no medical intervention (30%) (table R2). Of the patients who experienced adverse events, only 1 (10%) received medical intervention - epinephrine. No life-threatening events or deaths occurred. Within 90 days of receiving a monoclonal antibody, 15 patients (15.9%) required additional medical care for ongoing COVID symptoms (table R3). Eight (53.3%) of these were either hospitalized or received escalation of care while already in the hospital. Classification of adverse events by grade and monoclonal antibody. Grade I events are defined as mild and generally not bothersome. Grade II events are defined as moderate: bothersome, but not dangerous. Grade III events are defined as medically significant, but not immediately life-threatening, and often require medical intervention. Patients who required additional medical care for ongoing COVID-19 symptoms within 90 days of receiving a monoclonal antibody. Conclusion. Overall, monoclonal antibodies are safe, largely well-tolerated COVID-19 therapies in high-risk adolescent and young adult populations.
ABSTRACT
Purpose: Solid organ transplant recipients are at high risk of morbidity and mortality from coronavirus disease 2019 (COVID-19) with mortality rates as high as 30% reported in the early pandemic period. COVID-19 vaccine efficacy in the immunosuppressed population is lower than the general population. Early studies suggest that monoclonal antibody (MAB) treatment against the SARS-CoV-S spike protein may decrease hospitalizations and emergency department (ED) visits. Herein, we report our single center experience with use of MAB for COVID-19 treatment in kidney transplant recipients. Method(s): We performed a retrospective chart review of all kidney transplant recipients who developed COVID-19 from March 17, 2020 to January 26, 2022 at our transplant center. Date of diagnosis, vaccine status, MAB treatment, hospitalization and patient outcome was reviewed. Result(s): Two hundred ninety-one kidney transplant recipients had positive testing for SARS-CoV-2 in the period reviewed. 120 (41%) patients received MAB treatment. One patient death, not COVID related, was excluded from analysis. Of those who received MAB treatment, 99.2% survived compared to 82.4% of those who did not (p=0.00), Figure 1. Hospitalization was lower in those who received MAB (18.3% vs 60.8%, p=0.00). Completion of vaccine series, defined as 2 doses of mRNA or 1 dose of Janssen vaccine prior to infection, was also associated with better survival (98.6% vs 80.3%, p=0.00), Figure 1. Hospitalization rate was lower in those who completed vaccination prior to infection with SARS-CoV-2 (27.1% vs 59.2%, p = 0.00). The combination of MAB therapy and completion of vaccination also decreased hospitalization compared to those who received MAB but did not complete vaccines series (14% vs 26.8%, Table 1). Subgroup analysis of 143 patients infected from December 2021 to Jan 26, 2022 which may have reflected the Omicron surge was performed (Table 2). Treatment with MAB was associated with a reduction in hospitalization (11.6%) compared to 44.6% in those who did not receive MAB. Conclusion(s): MAB treatment for COVID-19 and prior vaccination were associated with improved survival and decreased risk of hospitalization in kidney transplant recipients.
ABSTRACT
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: Persistent acute symptoms of coronavirus disease 2019 (Covid-19) have been previously described in patients receiving immunosuppression, and have additionally been associated with the development of new variants of the SARS-CoV-2 virus. Here follows a report of a similar case which eventually responded to treatment with antiviral and monoclonal antibody therapies. CASE PRESENTATION: The patient is a 51 year old male with a past medical history of bilateral optic neuritis (treated with rituximab), polysubstance use disorder, bipolar disorder, and hypertension. He initially presented to the emergency department in January 2022 with symptoms of shortness of breath, cough, and worsening fatigue over the preceding 3-4 weeks. On presentation he required intubation for hypoxia. A PCR test for SARS-CoV-2 returned positive and he was initiated on treatment with intravenous dexamethasone and antibiotics for presumed community acquired pneumonia. He was extubated 4 days later, but remained hospitalized for a further 6 weeks due to recurrent fevers and a persistent supplemental oxygen requirement. Due to concern for viral-induced cryptogenic organizing pneumonia he was started on high-dose intravenous steroids. However, he developed escalating oxygen requirements resulting in a second intubation to facilitate bronchoscopy, results of which were non-diagnostic. Serum testing for SARS COV2 IgG antibody, 10 weeks after the initial onset of his symptoms, returned negative, therefore he was then treated with a 5 day course of remdesivir, as well as monoclonal antibody therapy with casirivimab-imdevimab. He additionally underwent a VATS lung biopsy for definitive tissue diagnosis, which revealed interstitial inflammation with patchy fibroblastic linear nodules, consistent with diffuse alveolar damage. He was extubated and had improvement in his oxygen requirements and respiratory function, and was planned for discharge to pulmonary rehabilitation almost 3 months after his initial presentation. DISCUSSION: Patients receiving immunosuppression remain at risk for persistent symptoms, prolonged hospitalization, and increased morbidity and mortality, when infected with SARS-CoV-2. Notably, the patient described here had received only 2 doses of an FDA-approved COVID-19 vaccine at the time of his infection, and was being treated with rituximab for optic neuritis, with his last infusion being approximately one month before the onset of his symptoms. Such prolonged, symptomatic infection from SARS-CoV-2 remains a clinical concern, especially due to its association with the development of new viral variants, and further research into appropriate treatment for these patients continues to be investigated. CONCLUSIONS: This case demonstrates an immunocompromised patient with persistent symptoms of Covid-19 who eventually responded to treatment with the antiviral remdesivir, as well as monoclonal antibodies. Reference #1: Choi B, Choudhary MC, Regan J, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med 2020;383:2291-2293. DISCLOSURES: No relevant relationships by Vivek Sinanan