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Objectives: Social determinants of health (SDoH) including income, education, employment, and housing are known to affect health outcomes;while use in real-world database studies are limited. This study assessed socioeconomic differences in burden of disease and utilization of COVID-19 specific medications in a large cohort of patients in the US. Method(s): A total of 17,682,111 patients having a COVID-19 diagnosis between 4/1/2020 and 4/30/2022 were identified in the IQVIA longitudinal medical and pharmacy claims databases of >277 million patients. For SDoH, a 3-digit zip code median Area Deprivation Index (ADI) (v2.0 University of Wisconsin School of Medicine and Public Health 2015) was calculated for each patient, maintaining patient privacy. The ADI is a validated tool ranking neighborhoods by socioeconomic disadvantage. Medical and pharmacy utilization was assessed and stratified by ADI pentiles, where 0-20 was the least disadvantaged, and 81-100 was the most disadvantaged. Result(s): The proportion of patients having a claim with COVID-19 diagnosis was higher in the most disadvantaged (7.75%) compared to the least disadvantaged group (5.94%) (US overall: 6.37%). Medical claims prior to COVID-19 diagnosis were highest in the least disadvantaged, while prior pharmacy utilization was highest in the most-disadvantaged group. There was sparse use of COVID-19 medications overall;the least disadvantaged patients had the lowest use of COVID-19 specific medications. Casirivimab/imdevimab use was highest in the 61-80 (2.01%) and 81-100 (1.79%) ADI groups, and remdesivir use was highest in the moderately disadvantaged (ADI 41-60 and 61-80) groups (both 2.33%). Utilization of hydroxychloroquine (unapproved for COVID-19) increased from 0.91% in the least to 2.13% in the most disadvantaged groups. Conclusion(s): This study shows unequal burden of COVID-19 prevalence by SDoH, with the most disadvantaged having a higher disease burden and utilization of certain approved and unapproved COVID-19 medications, highlighting the need for further study of the reasons for these disparities.Copyright © 2023
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Objectives: COVID-19 infected over 150 million people and caused over 1 million deaths in the US. This study evaluates several variables thought to be associated with mortality risk in the COVID-19 population. Method(s): The IQVIA longitudinal medical and pharmacy claims databases identified 17,682,111 patients with a COVID-19 diagnosis between 4/1/2020-4/30/2022 from a population of >277 million patients in the US. Patients were linked to Veritas Data Research fact-of-death records (90% complete compared to CDC reporting) and confirmed deaths were flagged. Confirmed mortality rates (CMR) were evaluated by age group, socioeconomic status (SES) using the Area Deprivation Index (v2.0, University of Wisconsin, 2015), co-morbidities and COVID-specific (approved and unapproved) treatments. Result(s): Of the 563,744 patients (3.2%) identified as dead (3.67% in men, 2.85% in women overall), CMR was lowest in patients aged 0-17 (0.08%), highest in age 65-75 (5.92%) and >75 (16.40%). Patients in the lowest 40% of SES had CMR of 4.43% while in the highest 20% was 1.56%. Respiratory failure, pneumonia and sepsis were the most common acute diagnoses accompanying COVID-19 deaths in all SES. In patients with comorbid dementia or Alzheimer's disease, CMR were 21.62% and 23.40% respectively. Additionally, congestive heart failure (15.79%), atrial fibrillation (15.50%), chronic kidney disease (15.30%) and COPD (12.19%) were associated with high CMR. Among patients receiving approved therapies, casirivimab/imdevimab and remdesivir had CMR of 1.41% and 12.63% respectively, while for those receiving unapproved therapies, ivermectin and hydroxychloroquine had CMR of 2.54% and 2.45%. Conclusion(s): Compared to the 1.1% case-mortality rate (Johns Hopkins 2023) among US COVID-19 patients, we found CMR exceeded 3% among those with a medical claim for COVID-19. Advanced age, dementia, and cardio-renal disease were associated with mortality. Patients with the lowest SES had approximately 3 times the confirmed mortality rate compared to those in the highest SES group.Copyright © 2023
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Objectives: According to the CDC, as of December 2022, almost one in three Americans had confirmed COVID-19 infection;yet only a small portion generated healthcare claims related to COVID-19. Higher burden of COVID-19 cases in Northeastern states compared to other US regions has been documented. This study examined the regional variation in demographic characteristics and treatment patterns among patients with a claim for COVID-19 in a nationwide US claims database. Method(s): Analysis of data from over 277 million patients in IQVIA's longitudinal medical and pharmacy claims databases resulted in a cohort of 17,682,111 patients with COVID-19 diagnosis between 4/1/2020 and 4/30/2022. Demographic characteristics and treatment rates for key approved and un-approved COVID-19 therapies were assessed and stratified by region. Result(s): Among patients in the database, 6.4% had a COVID-19 diagnosis. The proportion was higher in the Northeast (7.1%) and South (6.9%) compared with the West (4.8%). The highest proportion of patients were aged 18-44 years (32.7% in South to 35.2% in West). Over a fifth of the patients were >= 65 years old (US overall= 23.7%;22.5% in Northeast to 25.8% in Midwest). Approximately 57% of the patients nationally and within each region were women. For approved medications, utilization ranged from 1.7% in Northeast to 2.7% in Midwest (overall:2.2%) for remdesivir;0.7% in Northeast to 2.2% in South (overall: 1.5%) for casirivimab/imdevimab. For unapproved medications, utilization ranged from 0.9% in Northeast to 1.6% in South (overall:1.3%) for hydroxychloroquine and 0.4% in Northeast to 1.8% in South (overall:1.1%) for ivermectin. Conclusion(s): Less than one in five US cases of COVID-19 had a claim with diagnosis of COVID-19. Use of COVID-19 specific medications remained low throughout the pandemic. Despite the higher disease burden, proportion of patients with claims and receiving COVID-19 treatment were low nationally, particularly in the northeast US region.Copyright © 2023
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In December 2022, the Council of Experts was held. It purpose was to determine the place of virus-neutralizing monoclonal antibodies (NMA) in the ethiotropic treatment of COVID-19 in vulnerable categories of patients. The main issues were identified and their solutions were proposed. At the first visit of pregnant women due to COVID-19, proactive identification of risk factors and early prescription of NMA are recommended, preferably - with published safety data in this category of patients (casirivimab + imdevimab). In patients with oncological and other chronic (rheumatology, pulmonology, gastroenterology) diseases, prophylactic use of NMA is recommended. regardless of the severity of the disease. For patients with chronic pathology regardless of the severity of the disease an early prescription of ethiotropic therapy must be provided, combating the long-term circulation of the virus. To solve the problem of late treatment prescription, it is necessary to: use rapid tests, prescribe NMA if indicated, even if the patient presents late, introduce digital technologies to transfer information about COVID-19 cases between healthcare institutions (HI), create call centers for primary triage of patients, daily hospitals to reduce the burden on the HI. The issue of NMA using related to changes in their activity against new variants of SARS-CoV-2 remains relevant. Among the proposed solutions are: priority of indications over information about the activity of NMA, the diversification of the choice of NMA in HI, taking into account clinical experience, indications for use and prognosis of NMA activity, the use of combined forms of NMA (for example, casirivimab + imdevimab) or a combination of NMA with other means of ethiotropic therapy.Copyright © 2023, Dynasty Publishing House. All rights reserved.
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Passive immunization with mAbs has been employed in COVID-19. We performed a systematic review of the literature assessing the endogenous humoral immune response against SARS-CoV-2 in patients treated with mAbs. Administration of mAbs in seronegative patients led to a reduction in both antibody titres and neutralizing activity against the virus.Copyright © 2022
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X-linked inhibitor of apoptosis (XIAP) deficiency is a primary immunodeficiency associated with recurrent hemophagocytic lymphohistiocytosis (HLH) episodes. The clinical phenotypes of XIAP deficiency vary, ranging from splenomegaly to life-threatening inflammation. We report a case of XIAP deficiency with unusual late-onset HLH presentation likely triggered by a drug allergy. A previously healthy adolescent boy presented to the hospital with fever and rash seven days after starting antibiotics for a neck abscess. Laboratory evaluation demonstrated cytopenias, elevated liver enzymes, and increased inflammatory markers. Initially, antibiotics were discontinued due to concern for drug rash. He continued to deteriorate clinically and became hypotensive. Additional testing revealed decreased NK cell function, as well as elevated ferritin, triglycerides, and soluble IL-2 receptor. SLAM-Associated Protein (SAP) and XIAP evaluation by flow cytometry demonstrated decreased XIAP expression. Subsequently, genetic testing revealed a known pathogenic mutation in BIRC4 (c.421_422del), confirming the diagnosis of XIAP deficiency.Copyright © 2023
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Background & Purpose: Pregnant women are at higher risk of developing severe COVID-19 compared with non-pregnant women, particularly in the third trimester1. Despite ongoing campaigns, the proportion of pregnant women vaccinated against SARS-CoV-2 is lower than in the general population2. The medium-term effects of COVID-19 during pregnancy are not well characterized. We report a cohort of pregnant women admitted to hospital with moderate-to-severe COVID-19. Method(s): Data from clinical records were retrospectively collected from all pregnant women admitted through the maternity assessment unit at St. Thomas' Hospital, between January 2021 and January 2022, due to COVID-19 requiring oxygen to maintain saturations >94%. Result(s): Fourteen women were identified (age=33.4+/-5.2 years;42.8% Caucasian;28.6% Black), requiring admission at 31+/-4.7 weeks gestation. Only two were double vaccinated (14.2%). Body mass index (BMI) was 27.2+/-6.4 kg/m2. Two women had concomitant co-morbidities (asthma and type 1 diabetes). They were managed in the obstetric high- dependency unit (level 1), barring one that required invasive ventilation for one day. The Delta variant was most commonly implicated (43%). All women requiring oxygen received steroids. Four women received Tocilizumab and three casirivimab/imdevimab;two received both. Four women were delivered by emergency Caesarean section due to maternal or fetal concerns, while the others continued their pregnancies. There was one late intrauterine death at 35 weeks. Women were followed-up for an average of six weeks. At follow-up in the obstetric medicine COVID-19 clinic, all women had complete resolution of COVID-19 on clinical examination, pulse oximetry and chest radiograph. Conclusion(s): In 14 pregnant women requiring admission to hospital for hypoxia secondary to moderate-to-severe COVID-19, concomitant co-morbidities and high BMI were not prevalent. Most were not vaccinated against SARS-CoV-2. Despite experiencing moderate-to-severe COVID-19, they had complete clinical and radiological resolution at six weeks follow-up.
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The proceedings contain 48 papers. The topics discussed include: statin use and risk of rheumatoid arthritis or osteoarthritis in type 2 diabetes mellitus: a propensity score-matched population-based study;oxidative stress index as predictive marker for disease progression and its correlation with proinflammatory cytokines and lymphocyte subsets in COVID-19;translating pharmacological developments into clinical practice: case study of Ronapreve for COVID-19;finding a cost-effective alternative from commonly used dipeptidyl peptidase-4 inhibitors in India: a systematic study;older adult psychiatry patient medication education SusQI 2021;how much data for prescribers of new medicines are derived from studies in healthy volunteers?;how much data for prescribers of new medicines are derived from studies in healthy volunteers?;and the interactive walkway provides sensitive biomarkers for drug effects on (adaptive) walking in healthy elderly volunteers.
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Introduction: Favipiravir and remdesivir are antiviral drugs being used in the present pandemic and were also used previously for other viral infections in the past. Monoclonal antibody (Mab) Casirivimab-Imdevimab is a Coronavirus Disease 2019 neutralising antibody approved in the last one year. Therefore, a clinical comparison with the existing treatment modalities is imperative. Aim: To compare Mab with remdesivir and favipiravir for mild to moderate COVID-19 disease. Materials and Methods: A retrospective, observational and single-centre study was conducted at a COVID-19 infection facility and private tertiary care hospital, Mumbai, Maharashtra, India. Data of patients admitted during the period of 1st June 2021 to 31st August 2021 was collected and analysed in the months of September 2021 and October 2021. Adults participants diagnosed to have COVID-19 infection, not requiring critical care or oxygen therapy were included in the study. Time to recovery from treatment onset and the need for treatment escalation were the primary outcome measures. Data was entered into Microsoft Excel spreadsheet version 16 and analysed. Statistical analysis was carried out using Chi-square test for the significance of association between tabulated values of data for qualitative and categorical data. Two-tailed unpaired t-test and Analysis of Variance (ANOVA) was used for quantitative tabulated data. Results: This study included 158 participants, grouped into remdesivir(n=63),favipiravir(n=30)andMab(n=65)treatmentgroups. Gender distribution was comparable in all groups (p-value=0.08). The three groups were compared for need of treatment escalation and time of recovery. The Mab treatment group (on comparing with other treatment arms) had earlier symptom recovery when given to patients with mild COVID-19 disease (p-value=0.006 for major symptoms) or when treatment was started within five days of symptom onset (p-value <0.001). Patients in Mab treatment group with mild illness required no treatment escalation compared to other groups (p-value=0.011). However, time to recovery patients in all treatment groups was comparable in case of patients with moderate COVID-19 illness (p-value=0.7381). In patients with moderate COVID-19 illness Mab treatment group required more frequent treatment escalation compared to remdesivir treatment group (p-value=0.044), when treatment was started within 5 days of symptom onset remdesivir and mab were comparable for treatment escalation (p=0.144). Vaccination status of the three groups differed significantly (p-value=0.033) hence a further subanalysis was done. On further analysis, non-vaccinated patients receiving Mab recovered from minor symptoms (p-value=0.0006) earlier than those receiving Remdesivir. Amongst the participants of the Mab treatment-group, vaccinated and non-vaccinated patients had comparable recovery time and need for treatment escalation (p-value=0.57 and p-value=0.76, respectively). Participants who received Mab-treatment within five days of symptom onset;recovered earlier compared to those who received Mab treatment after five days (p-value=0.019). Conclusion: Monoclonal antibody treatment group compared to the other treatment groups had earlier recovery in non vaccinated patients, mild COVID-19 disease, and when treatment was started before or on the 5th day of symptom onset.
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Background: Information regarding effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant strains on clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in pregnant women is limited. Methods: A retrospective observational study was conducted using the data from the nationwide COVID-19 registry in Japan. We identified pregnant patients with symptomatic COVID-19 hospitalized during the study period. The Delta and Omicron variants of concern (VOC) predominant periods were defined as August 1 to December 31, 2021 and January 1 to May 31, 2022, respectively. Clinical characteristics were compared between the patients in the Delta and Omicron VOC periods. In addition, logistic regression analysis was performed to identify risk factors for developing moderate-to-severe COVID-19. Results: During the study period, 310 symptomatic COVID-19 cases of pregnant women were identified;111 and 199 patients were hospitalized during the Delta and Omicron VOC periods, respectively. Runny nose and sore throat were more common, and fatigue, dysgeusia, and olfactory dysfunction were less common manifestations observed in the Omicron VOC period. In the multivariable logistic regression analysis, onset during the later stage of pregnancy (OR: 2.08 [1.24–3.71]) and onset during the Delta VOC period (OR: 2.25 [1.08–4.90]) were independently associated with moderate-to-severe COVID-19, whereas two doses of SARS-CoV-2 vaccine were protective against developing moderate-to-severe COVID-19 (OR: 0.34 [0.13–0.84]). Conclusions: Clinical manifestations of COVID-19 in pregnant women differed between the Delta and Omicron VOC periods. SARS-CoV-2 vaccination was still effective in preventing severe COVID-19 throughout the Delta and Omicron VOC periods. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
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In the 1930's the corona virus was first identified as a highly contagious chicken respiratory virus. Two human coronaviruses were later identified, the human coronavirus 229E causing the flu and secondly the human coronavirus OC43. Others are also important as SARS-CoV. In late 2019 the outbreak of Pneumonia occurred in the Chinese city of Wuhan which was investigated as a result of the corona virus, renamed as 2019-nCoV by the World Health Organization (WHO) and. now called as SARS-CoV-2. The WHO has identified the global health problem as an epidemic. Respiratory droplets produced during coughing and sneezing are the main means of transmission of COVID-19. Infection with COVID-19 in an infected person may remain undetected. Common symptoms of fever and dry cough are less common in the production of sputum, fatigue and in some cases may be dyspnoea or shortness of breath. The COVID-19 virus is a type of RNA virus, the outer envelope containing a lipid bilayer in which various proteins are synthesized such as membrane (M), envelope (E) and spike (S). Hand washing, coughing, social isolation, wearing a face mask in public, disinfection areas, and isolation are various ways to prevent the disease. The diagnosis of COVID-19 can be made on the basis of symptoms and confirmed using reverse transcription polymerase chain reaction (RT-PCR) tests. There are currently no antiretroviral drugs approved for COVID-19, only symptomatic and supportive treatment is used to treat people with this viral infection. Drugs that have been approved for the purpose of treating other viral infections are under investigation. Vaccination is an ultimate prevention and protection;few vaccines are given emergency approval and some are in progressive development phase in various countries to prevent this deadly pandemic.
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The lack of effective etiotropic therapy is a serious challenge in the treatment of patients with COVID-19. The recent emergence of a new class of medications neutralizing monoclonal antibodies against the SARS-CoV-2 spike protein allows to partially solve this problem. This article presents a clinical case of a patient with an increased risk of COVID-19 complications (paroxysmal atrial fibrillation, atherogenic dyslipidemia, impaired carbohydrate tolerance) who was treated with 600 mg casirivimab and 600 mg imdevimab by intravenous infusion. A significant improvement in the patient's well-being was noted within the first 24 hours: normalization of body temperature, stool, reduction of weakness, disappearance of arthralgia and myalgia. After 48 hours, a negative test result for SARS-CoV-2 RNA was obtained, which altogether made it possible to state the recovery. There were no adverse events during and after therapy. The casirivimab and imdevimab monoclonal antibody combination may be considered as a promising etiotropic treatment for COVID-19. Copyright © 2022, Dynasty Publishing House.
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Numerous therapeutic and prophylactic interventions are tried being developed and tried for COVID-19, from repurposed drugs, antivirals to immunotherapy including convalescent serum, vaccines and monoclonal antibodies to reduce the global burden of the disease. Vaccine-derived immunity develops over time and remains as the primary option for prophylaxis. Administration of neutralizing mAbs is an immediate and passive immunotherapy with the potential to reduce disease progression, hospitalizations and death. Antibody-based treatments are likely to be more effective if used during the early phase of the illness. Casarivimab together with Imdevimab, holds emergency use authorizations in several countries globally and in India. This review discusses the mechanism of action, current clinical indications, dose, use with other medications and vaccines, duration of protection, protection against variants and evidence of Casarivimab and Imdevimab monoclonal antibody cocktail therapy for mild to moderate COVID-19 patients. Copyright All © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research.
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Purpose: Kidney transplant recipients are at high-risk for severe coronavirus disease 2019 (COVID-19). Studies suggest that intervention with monoclonal antibody (MAB) treatment may decrease hospitalization rates. Here we describe a single-center experience of the use of casirivimab-imdevimab, a currently approved MAB, for treatment of COVID-19 disease in kidney transplant recipients. Method(s): This is a retrospective single center study of adult kidney transplant patients who were diagnosed with mild to moderate COVID-19 and received casirivimab-imdevimab as an outpatient infusion between 12/29/20 to 10/20/21. All patients had at least 30 days of study follow-up from date of infusion. Result(s): 69 patients were included with the following characteristics: 65.2% male, 73.9% white, mean age 50+/-13 years, 33% diabetic. Median time from transplant to COVID-19 diagnosis was 80 (IQR 33-143) months. 49.3% of patients were not vaccinated for COVID-19 while 1.5%, 34.8%, and 14.5% had received 1, 2 and 3 doses, respectively. Median time from COVID-19 diagnosis to MAB treatment was 3 (range 0-9) days. Of the 69 patients, 3 (4.3%) required hospitalization within 30 days after MAB infusion (table). There were no emergency department-only visits within 30 days after MAB infusion. There were no deaths, graft losses, or acute rejection episodes recorded in the 30-day follow-up period. One infusion reaction of flushing and palpitations was reported. Conclusion(s): To our knowledge, this study describes the largest cohort of kidney transplant recipients treated with casirivimab-imdevimab and demonstrates that among high-risk, immunosuppressed patients with COVID-19, casirivimabimdevimab therapy is associated with low rates of hospitalization and a favorable safety profile.
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Purpose: Kidney transplant(KTx) recipients are at increased risk of COVID-19 related complications. KTx pts who have undergone therapy to induce tolerance are a unique cohort regarding SARS-CoV-2 susceptibility, clinical course following infection, and vaccine response. We have reported results of a phase 2 trial to induce tolerance through establishment of durable donor whole blood and T-cell chimerism using FCR001, an investigational cell therapy. Pts received nonmyeloablative conditioning, LD KTx, FCR001 infusion and weaning of IS as previously described (Leventhal et al STM 2012). Full withdrawal of immunosuppression (IS) was possible in 26 of 37 pts, with a low (5.5%) risk of graft versus host disease (GvHD). We evaluated the impact of COVID-19 infection and vaccination response in this cohort. Method(s): A chart review of pts was conducted;variables of interest included demographic data, clinical course, and virologic assays. Result(s): We identified 28 evaluable pts (Figure 1), 7 of which tested Covid positive. No infected pts were hospitalized;there was no evidence of renal function impairment, mean eGFR pre-infection was 57.83 mL/min/1.73 m2 and post-infection was 59.25 mL/min/1.73 m2. No change in chimerism was seen with infection. Three infected pts received casirivimab/imdevimab. Reported symptoms during COVID-19 infection were mild (Table 1). 22 pts have been vaccinated (16 Pfizer-BioNtech, 3 Johnson&Johnson(J&J), and 3 Moderna). 4 pts had serology performed (Table 2). Vaccination was well tolerated with no loss of chimerism. Conclusion(s): No KTx/FCR001 pts with COVID-19 developed a severe disease type. Infection in pts off IS was not associated with loss of chimerism. SARS-CoV-2 vaccination resulted in strong humoral responses and did not lead to loss of chimerism or allograft dysfunction.
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Purpose: The risk of severe COVID-19 requiring hospitalization and death is higher in solid organ transplant recipients (SOTr). There remains limited data on the use of monoclonal antibodies and long-term outcomes in SOTr. Method(s): This is a retrospective study conducted at Jackson Health System-Miami Transplant Institute in SOTr with mild-moderate COVID-19, from November 2020 to October 2021. Bamlanivimab was used initially for outpatients with mild to moderate COVID-19 but switched to casirivimab/imdevimab on March 1, 2021, due to rising prevalence of SARS-CoV-2 variants in the Miami-Dade area. Outcomes assessed included emergency department visits, hospitalizations, allograft rejection, and death. Result(s): Ninety-two patients were treated, most commonly with casirivimab/imdevimab (74%). The median age was 51 (range, 18-81) years, with 61% male and 60% Hispanic ethnicity. Transplanted organs included 68 kidney (74%), 10 liver (10.8%), 10 heart (10.8%), and 7 lung (7.6 %). Forty-two (45.6%) had a vaccine breakthrough infection, of which 34 (80.9%) were during the delta variant predominance. The median time from positive SARS-CoV-2 test to administration of monoclonal antibody was 1 (range, 0 - 10) day. Anti-metabolite agents were decreased or held in 54.3% of cases. Median follow-up was 116 (range, 19 - 358) days. Five (5.8%) patients had an emergency department visit, 26 (28.2%) were hospitalized;of which 11 (42%) were due to worsening COVID-19 symptoms within 28-days of infusion. 63.6% (7/11) required supplemental oxygen, none required mechanical ventilation. The median hospital length of stay was 6 (range, 2-32) days and all patients were discharged alive. During follow-up, 6 (4 kidney, 2 heart;6.5%) developed biopsy proven rejection. No graft loss or death occurred in this cohort. Conclusion(s): Early use of monoclonal antibodies in SOTr is associated with favorable outcomes. Multi-center studies assessing use of monoclonal antibodies in breakthrough infections and association with allograft rejection are needed.
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Purpose: At the beginning of the pandemic, kidneys from SARS-CoV-2 (COVID) RT-PCR positive donors were not utilized for transplantation, due to the risk of viral transmission. With the advent of the COVID vaccines, and improved monoclonal antibody therapy we transplanted organs from COVID positive donors irrespective of disease severity. Method(s): We performed six kidney transplants from COVID RT-PCR positive donors. Potential donors were screened for the date of the first positive COVID RTPCR. Only donors whose test had been positive at least 10 days prior to donation on a nasopharyngeal swab or bronchoalveolar lavage were accepted. A cycle threshold (ct)of >= 35 cycles was used as a cut off for accepting kidneys, when results were available prior to donation. Disease severity was not considered in donor evaluation. Recipient selection was performed based on willingness to give informed consent for the use of such kidneys, prior vaccination with at least 2 doses of the COVID vaccine and negative RT-PCRs in the month prior to transplantation. Result(s): We successfully transplanted 6 recipients from 5 donors. While one of the kidneys was recovered locally, the remainder were imported as non mandatory nationally shared organs. Four donors suffered from ARDS secondary to COVID pneumonia. Two donors were on ECMO at the time of donation. Two of the 5 donors were DCD recoveries with warm ischemic times times of 22 and 28 minutes. Co-infections in the donors included Candida glabrata, Enterococcus faecalis, and Burkholderia Cepacia for which appropriate prophylaxis was used in the recipients. All donors had positive nasopharyngeal RT-PCRs. Three had positive bronchioloalveolar lavage RT-PCRs. One donor was RT-PCR negative at the time of donation. Three recipients were sensitized with a PRA of 48%, 96%and 100%. The mean cold ischemic time was 25 hours. The mean KDPI was 51%. The delayed graft function rate was 33%. There was no primary nonfunction, rejection, death or graft loss after median follow-up of 87 (30-250days). The mean recipient GFR was 43ml/min. Dual kidney transplants were performed in two recipients. None of the recipients developed a COVID infection. 5/6 recipients received monoclonal antibodies (casirivimab and imdevimab) immediately after reperfusion. One patient did not receive casirivimab and imdevimab as it was not yet available in our region. All 6 patients received Thymoglobulin induction. Conclusion(s): With careful selection of immunized recipients, clinical assessment of transmission risk, and the preemptive use of monoclonal antibodies post exposure , SARS-Cov-2 positive donor kidneys can be safely utilized for single or dual kidney transplantation, without an increased risk of viral transmission, rejection or graft loss.
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SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Much has been learned about the immune dysregulation and release of pro-inflammatory cytokines since the emergence of the COVID-19 pandemic.1 Patients with interstitial lung disease are often on immunosuppressive agents, such as rituximab, which is a B-cell depleting agent. There has been a large retrospective cohort study showing that rituximab therapy was the only immunosuppressive medication with a trend towards in-hospital death.2 We present a case of COVID-19 in a patient on rituximab with ANCA vasculitis. CASE PRESENTATION: A 51-year-old male, never smoker, with ANCA positive vasculitis (positive MPO and PR3) and interstitial lung disease (on 4-5L of oxygen) presented to the hospital with nausea and fever for 2 days and was found to have a positive SARS-CoV-2 PCR. At the time of presentation, he was on rituximab 1000 mg x 2 doses every 6 months with last infusion one month prior to presentation, azathioprine 150 mg daily, prednisone 15 mg daily, nintedanib 100 mg BID, and IVIG monthly. Spirometry showed FVC of 1.60L/37% predicted and an FEV1 1.28L/39% predicted. Patient had 2 COVID vaccinations and one booster (all Pfizer mRNA), the latter 3 months prior to presentation. On admission, he was saturating at 55% on 4L and placed on 15L non-rebreather;he was afebrile, normotensive, and with a pulse of 110 BPM. Exam was notable for a cough, wheezing, and tachypnea. Lab work was notable for positive SARS-COV-2 PCR, a total white blood cell count of 5.3x103 uL, and a normal hemoglobin and platelet count. He had a CO2 of 34, normal creatinine, and no transaminitis. Lactate dehydrogenase (LDH) was elevated at 318 U/L, and lactate was elevated at 3.5 mmol/L. His chest x-ray on admission demonstrated patchy filling opacities and low lung volumes. He received dexamethasone, remdesivir, and the monoclonal antibodies casirivimab and imdevimab (REGEN-COV) on the first day of admission. Patient also received his monthly IVIG dose inpatient. After a week, he was weaned back to his home oxygen and symptomatically back to baseline. Most recent PFTs on the same outpatient immunosuppressive regimen as prior to admission are unchanged. Patient received two doses of preventative monoclonal antibodies (EVUSHELD) 3 months after admission. DISCUSSION: Here we discuss a case of a patient with severe COVID-19 pneumonia requiring inpatient hospitalization despite three COVID mRNA vaccinations, likely secondary to difficulty in mounting an immune response to the vaccinations given his use of immunosuppressive medications. This is also an example of the early use of monoclonal antibodies in an inpatient with long term preservation of his underlying lung function.3 CONCLUSIONS: We recommend counseling and close observation of patients on rituximab due to risk of severe COVID-19 infection as well the use of preventative monoclonal antibodies (EVUSHELD). Reference #1: Jamal M, Bangash HI, Habiba M, Lei Y, Xie T, Sun J, Wei Z, Hong Z, Shao L, Zhang Q. Immune dysregulation and system pathology in COVID-19. Virulence. 2021 Dec;12(1):918-936. doi: 10.1080/21505594.2021.1898790. PMID: 33757410;PMCID: PMC7993139. Reference #2: Andersen, K. M., Bates, B. A., Rashidi, E. S., Olex, A. L., Mannon, R. B., Patel, R. C., Singh, J., Sun, J., Auwaerter, P. G., Ng, D. K., Segal, J. B., Garibaldi, B. T., Mehta, H. B., Alexander, G. C., Haendel, M. A., & Chute, C. G. (2022). Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: A retrospective cohort study using data from the National COVID Cohort Collaborative. The Lancet Rheumatology, 4(1), e33–e41. https://doi.org/10.1016/S2665-9913(21)00325-8 Reference #3: Weinreich, D. M., Sivapalasingam, S., Norton, T., Ali, S., Gao, H., Bhore, R., Xiao, J., Hooper, A. T., Hamilton, J. D., Musser, B. J., Rofail, D., Hussein, M., Im, J., Atmodjo, D. Y., Perry, C., Pan, C., Mahmood, A., Hosain, R., Davis, J. D., Yancopoulos, G. D. (2021). Regen-cov antibody combination and outcomes in outpatients with covid-19. New England Journal of Medicine, 385(23), e81. https://doi.org/10.1056/NEJMoa2108163 DISCLOSURES: Advisory Committee Member relationship with Genentech Please note: 2019-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Consulting fee Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2018-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2018-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Honoraria Consultant relationship with Genentech Please note: 2018-2020 by Ayodeji Adegunsoye, value=Consulting fee Removed 06/06/2022 by Ayodeji Adegunsoye No relevant relationships by Cathryn Lee No relevant relationships by Kavitha Selvan PI relationship with Boehringer-Ingelheim Please note: >$100000 by Mary Strek, value=Grant/Research Support PI relationship with Galapagos Please note: $70,000-100,00 by Mary Strek, value=Grant/Research Support Endpoint Adjudication Committee Member relationship with Fibrogen Please note: $1-$1000 by Mary Strek, value=Honoraria No relevant relationships by Rachel Strykowski
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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
ABSTRACT
SESSION TITLE: Global Case Reports in Critical Care SESSION TYPE: Global Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Our world has been ravaged by SARS-COV2 over 2 years resulting in mortality in excess of six million lives. More insights have been known in lights of pathophysiology, natural history and modalities of therapy. Cytokine release syndrome, as one of the most dreadful consequences after acute COVID-19 infection, can lead to severe ARDS and deaths. Typically, CRS happens in the first 5-10 days after the initial date on infection. Multiple modes of treatments have been proposed and become standard of care for this life-threatening condition. CASE PRESENTATION: 86 -year-old female with CAD, HTN, SSS, dementia developed 3-day history of fever with dyspnea (SpO2 75% on ambient air). COVID vaccine history was AZ, AZ and Moderna 1 month ago. She was admitted to ICU and placed on oxygen high flow FiO2 50%. She was promptly started on IV Remdesivir, Dexamethasone and Tocilizumab. Then, SARS-COV2 Omicron strain had dominated Thailand reaching almost 99%. Thus, she was given IV Sotrovimab. She gradually improved and was able to wean off from oxygen high flow. As we anticipate transferring her out of ICU once the RT-PCR for COVID-19 reached the safety threshold, those subsequent PCR tests have been in the range of active replication of virus. On ICU day 24, her condition deteriorated with fever spike and more dyspnea needed the use of O2 NHF once again. Studies had revealed that more virus replication and cytokine storm had resumed as evidenced by rising CRP and IL-6 level. This moment, we suspected that she could have contracted a Delta strain. Therefore, we decided to give IV Casirivimab/Imdevimab along with Dexamethasone for this second CRS. NP swab had been sent to Thai genomics lab to identify the virus strain. This time, she gradually recovered over 7 days. Finally, the RT-PCR on day 31 had been in the safe zone and she was discharged home. Subsequent result from genomic study had confirmation of Omicron strain of the COVID-19. DISCUSSION: Typically, cytokine storm after COVID-19 pneumonia happens within 7-10 days after the onset of infection. Without appropriate treatments, this can result in severe pneumonia/ARDS and eventual death. To our knowledge, after the successful treatment of the first wave of CRS, the patient should either recover gradually or succumb to the severe systemic effects. This case has highlighted that there can be a second wave of cytokine storm especially if the virus continued to replicate even with appropriate therapies. Repeated dose of antiviral drugs and possible a different kind of monoclonal antibody might come into role and can potentially save life in this uncommon event. CONCLUSIONS: We report an interesting case of CRS resulting in severe ARDS with unusually prolonged active viral replication despite of treatments. More surprisingly, this patient also had developed a double resurgence of cytokine storm from this particularly sustained viral replication. Reference #1: 1. David C. Fajgenbaum, M.D., and Carl H. June, M.D. Cytokine Storm N Engl J Med 2020;383:2255-2273 DOI: 10.1056/NEJMra2026131 Reference #2: 2. Yujun Tang, Jiajia Liu, […], and Chengping Wen Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies Front Immunol 2020;11:1708 DISCLOSURES: No relevant relationships by Kasem Sirithanakul