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1.
Mol Immunol ; 152: 215-223, 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2095806

ABSTRACT

Identification of immunologic epitopes against SARS-CoV-2 is crucial for the discovery of diagnostic, therapeutic, and preventive targets. In this study, we used a pan-coronavirus peptide microarray to screen for potential B-cell epitopes and validated the results with peptide-based ELISA. Specifically, we identified three linear B-cell epitopes on the SARS-CoV-2 proteome, which were recognized by convalescent plasma from COVID-19 patients. Interestingly, two epitopes (S 809-823 and R1ab 909-923) strongly reacted to convalescent plasma collected at the early phase (< 90 days) of COVID-19 symptom onset, whereas one epitope (M 5-19) reacted to convalescent plasma collected > 90 days after COVID-19 symptom onset. Neutralization assays using antibody depletion with the identified spike (S) peptides revealed that three S epitopes (S 557-571, S 789-803, and S 809-823) elicited neutralizing antibodies in COVID-19 patients. However, the levels of virus-specific antibody targeting S 789-803 only positively correlated with the neutralizing rates at the early phase (<60 days) after disease onset, and the antibody titers diminished quickly with no correlation to the neutralizing activity beyond two months after recovery from COVID-19. Importantly, stimulation of peripheral blood mononuclear cells from COVID-19-recovered patients with these SARS-CoV-2 S peptides resulted in poor virus-specific B cell activation, proliferation, differentiation into memory B cells, and production of immunoglobulin G (IgG) antibodies, despite the B-cells being functionally competent as demonstrated by their response to non-specific stimulation. Taken together, these findings indicate that these newly identified SARS-CoV-2-specific B-cell epitopes can elicit neutralizing antibodies, with titers and/or neutralizing activities declining significantly within 2-3 months in the convalescent plasma of COVID-19 patients.

2.
Transfusion ; 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2088356

ABSTRACT

BACKGROUND: It is important to maintain the safety of blood products by avoiding the transfusion of units with known and novel viral pathogens. It is unknown whether COVID-19 convalescent plasma (CCP) may contain pathogenic viruses (either newly acquired or reactivated) that are not routinely screened for by blood centers. METHODS: The DNA virome was characterized in potential CCP donors (n = 30) using viral genome specific PCR primers to identify DNA plasma virome members of the Herpesviridae [Epstein Barr Virus (EBV), cytomegalovirus (CMV), human herpesvirus 6A/B, human herpesvirus 7] and Anelloviridae [Torque teno viruses (TTV), Torque teno mini viruses (TTMV), and Torque teno midi viruses (TTMDV)] families. In addition, the RNA plasma virome was characterized using unbiased metagenomic sequencing. Sequencing was done on a HiSeq2500 using high output mode with a read length of 2X100 bp. The sequencing reads were taxonomically classified using Kraken2. CMV and EBV seroprevalence were evaluated using a chemiluminescent immunoassay. RESULTS: TTV and TTMDV were detected in 12 (40%) and 4 (13%) of the 30 study participants, respectively; TTMDV was always associated with infection with TTV. We did not observe TTMV DNAemia. Despite CMV and EBV seroprevalences of 33.3% and 93.3%, respectively, we did not detect Herpesviridae DNA among the study participants. Metagenomic sequencing did not reveal any human RNA viruses in CCP, including no evidence of circulating SARS-CoV-2. DISCUSSION: There was no evidence of pathogenic viruses, whether newly acquired or reactivated, in CCP despite the presence of non-pathogenic Anelloviridae. These results confirm the growing safety data supporting CCP.

3.
Cell Rep Med ; 3(11): 100811, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2082685

ABSTRACT

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP), a passive polyclonal antibody therapeutic agent, has had mixed clinical results. Although antibody neutralization is the predominant approach to benchmarking CCP efficacy, CCP may also influence the evolution of the endogenous antibody response. Using systems serology to comprehensively profile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) functional antibodies of hospitalized people with COVID-19 enrolled in a randomized controlled trial of CCP (ClinicalTrials.gov: NCT04397757), we find that the clinical benefits of CCP are associated with a shift toward reduced inflammatory Spike (S) responses and enhanced nucleocapsid (N) humoral responses. We find that CCP has the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function and that CCP-induced immunomodulatory Fc glycan profiles and N immunodominant profiles persist for at least 2 months. We highlight a potential mechanism of action of CCP associated with durable immunomodulation, outline optimal patient characteristics for CCP treatment, and provide guidance for development of a different class of COVID-19 hyperinflammation-targeting antibody therapeutic agents.

4.
SSRN;
Preprint in English | SSRN | ID: ppcovidwho-346234

ABSTRACT

A novel coronavirus disease, which is transmitted from human to human has quickly become the cause of the current worldwide health crisis. This virus is, also known as SARS coronavirus, belongs to the Coronaviridae family of viruses. The recent outbreak of acute respiratory disorders starting in Wuhan, China is found to be caused by this virus. The condition caused by it, known as COVID-19 has spread very rapidly all over the world, causing so many death. This led WHO on Mar 11, 2020, to designate it as a global pandemic. An update on the history, etiology, epidemiology, pathophysiology and preventive methods for COVID-19 such as masking, quarantine, and social distancing are discussed in this paper. Repurposed drugs, antibodies, corticosteroids, vaccination and plasma transfusion, are among the treatments explained in the study. Finally, the study discusses India’s COVID vaccination programme. The major aspects of this entire review are to describe COVID-19 infection, its prevention and treatment approach. Note:

5.
Front Immunol ; 13: 1008438, 2022.
Article in English | MEDLINE | ID: covidwho-2080155

ABSTRACT

Objectives: To determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP). Methods: Patients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models. Results: The majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models. Conclusion: This analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors.


Subject(s)
COVID-19 , Cytokines , Humans , Interleukin 1 Receptor Antagonist Protein , Interleukin-17 , Chemokine CCL3 , Tumor Necrosis Factor-alpha , Interleukin-6 , Interleukin-4 , Capsid , COVID-19/therapy , Becaplermin , Chemokine CXCL10 , Interleukin-2 , Interleukin-8 , Interleukin-9 , Granulocyte Colony-Stimulating Factor
6.
Tanaffos ; 21(1): 24-30, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-2073215

ABSTRACT

Background: Due to the critical condition of COVID-19, it is necessary to evaluate the efficacy of administrating convalescent plasma to COVID-19 patients. Therefore, we decided to design a clinical trial to investigate the effect of convalescent plasma of patients recovered from COVID-19 on the treatment outcome of COVID-19-infected patients. Materials and Methods: In this parallel randomized controlled clinical trial, patients in the intervention group received standard treatment plus convalescent plasma of patients recovered from COVID-19. We allocated 60 patients to each treatment group through balanced block randomization. Then, COVID-19 outcomes, vital signs, and biochemical parameters were compared between the two treatment groups by the independent t test and ANCOVA. Results: The mean age (SD) of the patients in the intervention and standard treatment groups was 52.84 (15.77) and 55.15 (14.34) years, respectively. Although patients in the intervention group reported more hospitalization days (11.45±5.86 vs. 10.42±6.79), death rates (26.67% vs. 18.13%), ICU admission (45 vs. 41.67%), and ARDS (11.67% vs. 3.33%), these differences were not statistically significant (P>0.05). Moreover, the two groups were homogenous in vital signs and biochemical parameters before and after treatment (P>0.05). Conclusion: The present study indicated that convalescent plasma therapy has no significant effect on the survival, hospitalization, and ICU admission of COVID-19 patients.

7.
Life (Basel) ; 12(10)2022 Oct 09.
Article in English | MEDLINE | ID: covidwho-2071605

ABSTRACT

BACKGROUND: COVID-19 convalescent plasma (CCP) is an important antiviral option for selected patients with COVID-19. MATERIALS AND METHODS: In this open-label, phase 2, clinical trial conducted from 30 April 2020 till 10 May 2021 in the Republic of North Macedonia, we evaluated the efficacy and safety of CCP in hospitalized patients. Treatment was with a single unit of CCP having an anti-RBD IgG concentration higher than 5 AU/mL. RESULTS: There were 189 patients that completed the study, of which 65 (34.4%) had WHO 8-point clinical progression scale score of 3 (requiring hospital care but not oxygen support), 65 (34.4%) had a score of 4 (hospitalized and requiring supplemental oxygen by mask or nasal prongs), and 59 (31.2%) had a score of 5 (hospitalized and requiring supplemental oxygen by non-invasive ventilation or high-flow oxygen). Mean age was 57 years (range 22-94), 78.5% were males, 80.4% had elevated body mass index, and 70.9% had comorbidity. Following CCP transfusion, we observed clinical improvement with increase rates in oxygenation-free days of 32.3% and 58.5% at 24 h and seven days after CCP transfusion, a decline in WHO scores, and reduced progression to severe disease (only one patient was admitted to ICU after CCP transfusion). Mortality in the entire cohort was 11.6% (22/189). We recorded 0% mortality in WHO score 3 (0/65) and in patients that received CCP transfusion in the first seven days of disease, 4.6% mortality in WHO score 4 (3/65), and 30.5% mortality in WHO score 5 (18/59). Mortality correlated with WHO score (Chi-square 19.3, p < 0.001) and with stay in the ICU (Chi-square 55.526, p ≤ 0.001). No severe adverse events were reported. CONCLUSIONS: This study showed that early administration of CCP to patients with moderate disease was a safe and potentially effective treatment for hospitalized COVID-19 patients. The trial was registered at clinicaltrials.gov (NCT04397523).

8.
New Microbiologica ; 45(1):62-72, 2022.
Article in English | Web of Science | ID: covidwho-2068238

ABSTRACT

Convalescent plasma (CP) therapy might be effective in patients with haematological malignancies and B-cell depletion. We report a single-centre experience of COVID-19 patients with non-Hodgkin lymphoma and absence of B-cells as a consequence of anti-CD20 therapy successfully treated with CP from October 2020 to May 2021. CP was given in the presence of pneumonia with respiratory failure despite standard treatment and consisted of three infusions on an alternate-day basis. A review of the current literature on this topic was also performed. Six patients were identified (median age 59.5 years (range 50-73)). The last anti-CD20 drug administration occurred 60 days before infection (range 0-360). CP was administered after a median of 51 days (range 9-120) from SARS-CoV-2 diagnosis, with an early improvement in all but one subject. We suggest a possible clinical benefit of convalescent CP treatment in COVID-19 patients with haematological malignancies and B-cell depletion having persistent/recurrent pneumonia.

9.
Open Access Macedonian Journal of Medical Sciences ; 10:1698-1705, 2022.
Article in English | EMBASE | ID: covidwho-2066674

ABSTRACT

BACKGROUND: The rapid worldwide spread of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) or COVID-19 pandemic from its epicenter;Wuhan was first reported in December 2019. Egypt reported its first COVID-19 case on February 14, 2020. Thereafter, Egypt scaled-up preventive measures, with a partial lockdown starting on March 25. Several therapeutic agents along with convalescent plasma transfusion (CPT) are under investigation and data from CPTs have been receiving a lot of attention, after Emergency approvals from the Food and Drug Administration suggesting that it may provide a clinical effect in the treatment of SARS-COV-2. IMPORTANCE: Early and effective treatment of COVID-19 is vital for control of SARS-CoV-2 infection. METHODS: Designs: An interventional, single-arm, and non-randomized clinical trial conducted in Egypt from April 15 to July 21, 2020. Settings: This was a multi-center study conducted in three hospitals in Egypt. Participants: A total of 94 COVID-19 laboratory-confirmed patients using quantitative real-time polymerase chain reaction were enrolled in the study. Intervention: All patients were administered with two plasma units (each unit is 200 cc). The volume of donated plasma was 800 cc. Main Outcome and measures: Primary measure was the degree of clinical improvement among the COVID-19 patients who received CPT within 7 days. RESULTS: A total of 94 patients were enrolled who received CPT either within 7 days or after 7 days of hospitalization. 82 were severely ill and 12 were critically ill. The average age remained 58 years (±standard deviation 15.1 years). Male were 69% and 49% patients got cured while 51% died with case fatality rate 51%. Seventy-five percent deaths were above 45 years of age. The symptoms were dyspnea (55%), fever (52%), cough (46%), and loss of taste and smell (21%), and cyanosis (15%). The most common co-morbidities among the <40 years remained diabetes mellitus (21%) and asthma (14%). Among 40–60 years hypertension (56%), diabetes mellitus (39%) and among >60 years age group hypertension (57%), and chronic heart disease (24%) were reported. CPT within 7 days remained significant as compared with the CPT after 7 days with the number of days to cure (p=0.007) and ICU stay (p = 0.008) among severely ill cured cases. CONCLUSIONS: Among patients with COVID-19 and severe or critical illness, the use of CPT along with routine standard therapy resulted in a statistically significant improvement when administered within seven days of hospital admission. However, plasma transfusion, irrespective of days to transfusion may not help treat critically ill patients. The overall mean time to cure in severely ill patients was 15 days if CPT provided within 7 days with 65% cure rate. TRIAL REGISTRATION: Clinical Intervention identifier: MOHP_COVID-19_Ver1.1 registered April 2020.

10.
Pharmaceutical Journal ; 306(7945), 2022.
Article in English | EMBASE | ID: covidwho-2065017
11.
Cells ; 11(19)2022 Oct 04.
Article in English | MEDLINE | ID: covidwho-2065730

ABSTRACT

Despite the advancement of vaccination and therapies currently available, deaths due to the coronavirus disease 2019 (COVID-19) are still heavily documented. Severely infected individuals experience a generalized inflammatory storm, caused by massive secretion of pro-inflammatory cytokines that can lead to endothelial dysfunction, cardiovascular disease, multi-organ failure, and even death. COVID-19 convalescent plasma (CCP) therapy, selected primarily based on anti-SARS-CoV-2 antibody levels, has not been as convincing as expected in the fight against COVID-19. Given the consequences of a dysfunctional endothelium on the progression of the disease, we propose that the selection of plasma for CCP therapy should be based on more specific parameters that take into consideration the effect on vascular inflammation. Thus, in the present study, we have characterized a subset of CCP that have been used for CCP therapy and measured their anti- or pro-inflammatory effect on human coronary artery endothelial cells (HCAECs). Our data revealed that the longer the time lapse between the onset of symptoms and the plasma donation, the more mitochondrial dysfunction can be evidenced. The concentration of blood endothelial cell extracellular vesicles (BEC-EVs) was increased in the plasma of young individuals with mild symptoms. This type of selected convalescent plasma promoted the activation of the blood vascular endothelium, as reflected by the overexpression of ICAM1 and NFκB1 and the downregulation of VE-Cadherin. We propose this mechanism is a warning signal sent by the injured endothelium to trigger self-defense of peripheral blood vessels against excessive inflammation. Therefore, these results are in line with our previous data. They suggest that a more specific selection of COVID-19 convalescent plasma should be based on the time of donation following the onset of the clinical symptoms of the donor, the severity of the symptoms, and the age of the donor. These characteristics are relatively easy to identify in any hospital and would reflect the concentration of plasma BEC-EVs and be optimal in CCP therapy.


Subject(s)
COVID-19 , Coronavirus Infections , Extracellular Vesicles , Pneumonia, Viral , Betacoronavirus , Biomarkers , COVID-19/therapy , Cytokines , Endothelial Cells , Humans , Immunization, Passive , Inflammation , Pandemics
12.
Front Med (Lausanne) ; 9: 915367, 2022.
Article in English | MEDLINE | ID: covidwho-2065563

ABSTRACT

While the biomarkers of COVID-19 severity have been thoroughly investigated, the key biological dynamics associated with COVID-19 resolution are still insufficiently understood. We report a case of full resolution of severe COVID-19 due to convalescent plasma transfusion. Following transfusion, the patient showed fever remission, improved respiratory status, and rapidly decreased viral burden in respiratory fluids and SARS-CoV-2 RNAemia. Longitudinal unbiased proteomic analysis of plasma and single-cell transcriptomics of peripheral blood cells conducted prior to and at multiple times after convalescent plasma transfusion identified the key biological processes associated with the transition from severe disease to disease-free state. These included (i) temporally ordered upward and downward changes in plasma proteins reestablishing homeostasis and (ii) post-transfusion disappearance of a subset of monocytes characterized by hyperactivated Interferon responses and decreased TNF-α signaling. Monitoring specific dysfunctional myeloid cell subsets in peripheral blood may provide prognostic keys in COVID-19.

13.
Front Med (Lausanne) ; 9: 822821, 2022.
Article in English | MEDLINE | ID: covidwho-2065543

ABSTRACT

Background: The convalescent plasma of patients who recover from coronavirus disease 2019 (COVID-19) contains high titers of neutralizing antibodies, which has potential effects on the viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and improving the prognosis of patients with COVID-19. The goal of this study was to clarify the effects of convalescent plasma therapy on the 60-day mortality and negative conversion rate of SARS-CoV-2 during the hospitalization of patients with severe and life-threatening COVID-19 infection. Methods: This was a retrospective, case-matched cohort study that involved patients with severe COVID-19 infections. The patients who received convalescent plasma therapy were matched by age, sex, diabetes, hypertension, heart failure, the onset of symptoms to hospital admission, respiratory support pattern, lymphocyte count, troponin, Sequential organ failure assessment (SOFA), glucocorticoid, and antiviral agents to no more than three patients with COVID-19 who did not receive convalescent plasma therapy. A Cox regression model and competing risk analysis were used to evaluate the effects of convalescent plasma therapy on these patients. Results: Twenty-six patients were in the convalescent plasma therapy group, and 78 patients were in the control group. Demographic characteristics were similar in both groups, except for the SOFA score. Convalescent plasma therapy did not improve 60-day mortality [hazard ratio (HR) 1.44, 95% CI 0.82-2.51, p = 0.20], but the SARS-CoV-2 negative conversion rate for 60 days after admission was higher in the convalescent plasma group (26.9 vs. 65.4%, p = 0.002) than in the control. Then, a competing risk analysis was performed, which considered events of interest (the negative conversion rate of SARS-CoV-2) and competing events (death) in the same model. Convalescent plasma therapy improved events of interest (p = 0.0002). Conclusion: Convalescent plasma therapy could improve the SARS-CoV-2 negative conversion rate but could not improve 60-day mortality in patients with severe and life-threatening COVID-19 infection. Clinical Trial Number: The study was registered at ClinicalTrials.gov (NCT04616976).

14.
Pharmaceutical Journal ; 306(7950), 2022.
Article in English | EMBASE | ID: covidwho-2064964
15.
American Journal of Transplantation ; 22(Supplement 3):644-645, 2022.
Article in English | EMBASE | ID: covidwho-2063525

ABSTRACT

Purpose: Immunocompromised hosts are at risk for severe complications or death from SARS-CoV-2 infection. Few studies describe the clinical features, outcomes and treatment strategies in this population across multiple sites. Method(s): A multi-center retrospective analysis from academic medical centers in the Midwestern US was conducted for hospitalized patients with SARS-CoV-2 infection. Data was collected electronically using standardized intake and 28-day follow up case report forms. The centers included Northwestern University, University of Nebraska, Cleveland Clinic, University of Chicago, Indiana University and University of Kansas. Result(s): The cohort included 272 patients hospitalized from March 2020 to November 2021. Demographics are in Table 1. Mean admission was 6.84 +/- 6.42 days after symptom onset. The most commonly reported symptoms were cough (71.4%), dyspnea (59.6%), fatigue (55.3%), fever (54.9%), and diarrhea (43.9%). Admission CXR had pneumonia in 31.6%;63% with multifocal or patchy opacities. 87 patients had a chest CT;72 (82.7%) showed pneumonia. 97 patients (36.1%) required ICU admission. Treatments included remdesivir (58.5%), dexamethasone (54.4%), convalescent plasma (3.0%), IL-6 inhibitor (4.5%). Immunosuppression management included holding (44.2%) or decreasing (26.6%) the dose of antimetabolite. 76 patients (28.3%) had documented bacterial co-infection, in blood (34.1%), lung (30.6%) and urine (30.6%). 6 (2.2%) patients experienced rejection within 30 days and 8 patients (3.0%) developed CMV viremia. 26 patients (9.7%) died by day 28. Conclusion(s): This cohort had high rates of ICU admission (36.1%), bacterial coinfection (28.3%), rehospitalization (31.5%) and mortality (9.7%).

16.
American Journal of Transplantation ; 22(Supplement 3):765, 2022.
Article in English | EMBASE | ID: covidwho-2063490

ABSTRACT

Purpose: The purpose of the study was to examine the clinical course, outcomes, and complications of COVID-19 in pediatric solid organ transplant patients from a single institution, with special attention to thrombotic complications, multiple inflammatory syndrome in children (MIS-C), and new rejection. Method(s): The medical record at our institution was retrospectively queried for all solid organ transplant patients up to 21 years old diagnosed with COVID-19 from March 2020 to September 2021. This cohort was compared in a 1:1 fashion with age, sex, and ethnicity-matched controls with COVID-19 infection, but no history of transplant. Categorical variables were analyzed with Chi-square or Fisher's exact test, and continuous variables were analyzed with Mann-Whitney test. Result(s): 44 solid organ transplant patients met study inclusion criteria. Six patients were excluded from analysis due to insufficient documentation of COVID-19 diagnosis or course. The cohort was composed of 17 kidney, 11 heart, six liver, two lung, one liver-kidney, and one multivisceral transplant patients. Median age at COVID-19 diagnosis was 15 years (IQR 9). Median time from transplant to COVID-19 diagnosis was 2.5 years (IQR 3.4). Of the 38 patients, 17 were white non-Hispanic/Latino (44.7%), 12 were Hispanic/Latino (31.6%), three were Black (7.9%), two were Asian (5.3%), three were other (7.9%), and one was unknown (2.6%). 19 patients (50%) were male. 12 transplant patients were asymptomatic (31.6%), compared to five controls (13.2%, p=0.054). Of the symptomatic patients, the most common symptoms in the solid organ transplant group were fever (26.3%) and headache (18.4%), with few patients experiencing shortness of breath (5.3%). Hospital (15.8%) and ICU (5.3%) admission rates were equal in both groups, with a median length of stay of 4.5 days for the transplant group (IQR 5.25) versus 4 days (IQR 5.75) for controls (p=0.59). 32 patients in each group received supportive care as outpatients (84.2%). A minority of transplant patients received monoclonal antibody (6.3%), convalescent plasma (6.3%), steroids (6.3%), and remdesivir (3.1%). There was one case of MIS-C in the transplant group (2.6%) versus three in the control group (7.9%) (p=0.62). One transplant patient developed COVID-associated microangiopathy (2.6%), but there were no thrombotic complications among controls (p > 0.99). There were no new cases of cellular or antibody-mediated rejection following COVID-19. There was one death in the transplant cohort, but no deaths in the control group. Conclusion(s): We report the largest multi-organ cohort of pediatric solid organ transplant recipients with COVID-19 to date. Our findings suggest pediatric solid organ transplant patients fare similarly to healthy children, without elevated risk of complications.

17.
American Journal of Transplantation ; 22(Supplement 3):1059, 2022.
Article in English | EMBASE | ID: covidwho-2063485

ABSTRACT

Purpose: The purpose of this study was to evaluate long term humoral and cellular immunity generated following SARS-CoV-2 infection in solid organ transplant recipients (SOTR). Method(s): Patients included had an active graft of an organ transplant as an adult, a positive polymerase chain reaction nasopharyngeal swab for SARS-CoV-2 after transplant, and had not received convalescent plasma, vaccination, or monoclonal antibody for SARS-CoV-2. Whole blood was obtained 6 months (+/- 1 month) after infection. Serology measured IgG and IgM titer to the SARS-CoV-2 spike protein receptor binding domain, reported as signal/ cut-off ratio (s/co). CD4+ and CD8+ T-cell reactivity was measured by Activation Induced Marker assays following stimulation of peripheral blood mononuclear cells with SARS-CoV-2 peptide pools encompassing the SARS-CoV-2 spike protein. Result(s): Of 25 subjects, 19 (76.0%) were hospitalized, 4 (16.0%) developed hypoxia, but none required mechanical ventilation. Biopsy-proven graft rejection occurred in 3 (12.0%), but none had graft loss. At 6 months, 8 (16%) had persistent symptoms and 2 (4.0%) were re-infected within one year. In the immunity study, 22 (88.0%) had reactive IgG testing and 11 (44.0%) had reactive IgM testing. Median IgG titer was 3.68 s/co (range 0.19-36.44) and IgM titer was 0.79 s/co (range 0.02-16.41). Virus-specific CD4+ T-cell reactivity was noted in 23 (92%), but only 10 (40.0%) had reactive CD8+ T-cell testing. Moderate correlation was observed between IgG and IgM titer (r=.51, p= 0.009) and between IgG titer and percent virus-specific CD4+ T-cells (r=.46, p=0.02). CD8+ T-cell reactivity was correlated with greater illness severity (p=0.043). Use of Tacrolimus, mycophenolate, or corticosteroids at time of infection was not associated with T-cell or antibody reactivity. Conclusion(s): In summary, this cohort of SOTR evaluated six months after noncritical COVID-19 illness demonstrated robust IgG and CD4+ T-cell responses, and CD8+ T-cell reactivity was correlated with higher disease severity.

18.
American Journal of Transplantation ; 22(Supplement 3):874-875, 2022.
Article in English | EMBASE | ID: covidwho-2063454

ABSTRACT

Purpose: To characterize demographics, treatment patterns, and outcomes among 3,998 transplant patients hospitalized for COVID-19 over 16 months of the pandemic (May '20-Aug '21). Method(s): Adult patients in a transplant cohort (TC) and non-transplant cohort (NTC) hospitalized with COVID-19 (ICD-10: U07.1) were compared in the Premier Healthcare Database from May '20-Aug '21. Baseline measures in first two days, demographics, comorbidity, COVID-19 treatments and immunosuppressants were analyzed. Outcomes included mortality (discharge status expired or hospice) and hospital and ICU LOS. Result(s): 3,998 TC patients were hospitalized for COVID-19 in 587 US hospitals. Compared to NTC, TC were younger (61 vs 64 yrs;p<.0001), less likely to be white (59% vs 67%;p<.0001), obese (24% vs 33%;p<.0001) or have COPD (17% vs 24%;p<.0001). TC had higher rates hypertension (84% vs 69%;p<.0001), renal disease (80% vs 22%, p<.0001), diabetes (48% vs 29%;p<.0001) and chronic heart failure (23% vs 18%;p<.0001). During hospitalization, a lower proportion of TC needed any oxygen therapy compared to NTC (p<.05). Compared to NTC, fewer TC received remdesivir (RDV) (44% vs 48%;p<.0001), but more received corticosteroids (87% vs 78%;p<.0001), anticoagulants (44% vs 29%;p<.0001) and convalescent plasma (18% vs 16%;p=0.007). In TC, 44% received MMF, 73% calcineurin inhibitors and 5% mTOR. Use of MMF did not change over time (43% May-Jul 2020;43% Aug- Dec 2020;45% 2021). TC had higher ICU admission rates (31% vs 28%;p.001), but similar hospital LOS and ICU LOS compared to NTC. All-cause mortality in NTC (15% overall;16% May-Jul 2020;16% Aug-Dec 2020;14% 2021) was not significantly different than TC over time (16% overall;13% May-Jul 2020;16% Aug-Dec 2020;16% 2021). Conclusion(s): Very few large studies have assessed COVID-19 management in transplant patients over time. All-cause mortality was comparable in both cohorts despite TC immunosuppression. RDV use was lower in TC. Uncertainty around MMF use in COVID-19 patients did not impact reported use of MMF. Further analyses are needed to evaluate confounding factors (medication sequence, time since transplant, disease severity) and impact of external factors such as earlier testing and treatment for COVID-19, vaccination, and new variants. (Table Presented).

19.
Vox Sang ; 117(10): 1202-1210, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2063958

ABSTRACT

BACKGROUND AND OBJECTIVES: The use of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) in the treatment of patients with severe acute respiratory syndrome-2 infection has been controversial. Early administration of CCP before hospital admission offers a potential advantage. This manuscript summarizes current trials of early use of CCP and explores the feasibility of this approach in different countries. MATERIALS AND METHODS: A questionnaire was distributed to the International Society of Blood Transfusion (ISBT) CCP working group. We recorded respondents' input on existing trials on early/outpatient CCP and out-of-hospital (OOH)/home transfusion (HT) practices in their countries and feedback on challenges in initiating home CCP infusion programmes. In addition, details of existing trials registered on clinicaltrials.gov were summarized. RESULTS: A total of 31 country representatives participated. Early/OOH CCP transfusion studies were reported in the United States, the Netherlands, Spain and Brazil. There were a total of six published and five ongoing trials on the prophylactic and therapeutic early use of CCP. HT was practised in Australia, the UK, Belgium, France, Japan, Nigeria, the Netherlands, Spain, Italy, Norway, the United States and some provinces in Canada. Thirty-four representatives indicated a lack of OOH CCP or HT in their institutions and countries. Barriers to implementation of OOH/HT included existing legislation, lack of policies pertaining to outpatient transfusion, and associated logistical challenges, including lack of staffing and resources. CONCLUSION: Early administration of CCP remains a potential option in COVID-19 management in countries with existing OOH/HT programmes. Legislation and regulatory bodies should consider OOH/HT practice for transfusion in future pandemics.


Subject(s)
COVID-19 , COVID-19/therapy , Feasibility Studies , Hospitals , Humans , Immunization, Passive/adverse effects , SARS-CoV-2
20.
Chest ; 162(4):A2571-A2572, 2022.
Article in English | EMBASE | ID: covidwho-2060966

ABSTRACT

SESSION TITLE: Pulmonary Issues in Transplantation Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: We describe two unvaccinated lung transplant recipients (LTRs) with mild COVID-19 and prolonged SARS-CoV-2 colonization who presented with recrudescence of symptoms due to superinfection. CASE PRESENTATION: Case 1: A 57-year-old LTR (August 2018) presented to the emergency room (ER) in July 2020 with headache, positive SARS-CoV-2 nasopharyngeal swab-PCR result, and elevated D-Dimer. He recovered at home and tested negative for SARS-CoV-2 on day 28. He presented to the ER again in October 2020 with chest pain. At this time, evaluation revealed a positive SARS-CoV-2 nasopharyngeal swab-PCR result, positive SARS-CoV-2 IgG (index 3.41), leukocytosis, and elevated inflammatory markers. Of note, nasopharyngeal swab was also positive for rhinovirus. Imaging showed new mild bibasilar ground-glass opacities. Patient was treated with remdesevir, convalescent plasma, and pulse corticosteroid. His SARS-CoV-2 PCR test was negative on day 3 of the remdesevir regimen;he remains clear of SARS-CoV-2 and rhinovirus to date, with complete clinical and radiologic recovery (Figure 1, Case 1). His immunosuppression was unchanged. Case 2: A 75-year-old LTR (July 2016) with pancytopenia presented for a sick visit in May 2020 with cough and fever. His SARS-CoV-2 nasal wash-PCR test was positive;imaging was unremarkable. He was sent home on pulse corticosteroid and levofloxacin. A week later in June 2020, he presented to the ER with worsening cough. At this time, evaluation revealed positive SARS-CoV-2 IgG (index 7.58), leucopenia, thrombocytopenia, elevated inflammatory markers, and new radiographic bibasilar ground-glass opacities (Figure 1, Case 2). His condition improved with intravenous antibiotics and corticosteroids. He consistently tested positive for SARS-CoV-2 in nasal wash samples for 3 months, with the first negative test in September 2020. He was hospitalized in January 2021 for neutropenic fever, P. Aeruginosa (PsA) infection in bronchoalveolar lavage (BAL), and anti-PsA antibodies in the serum. At this time, he also had SARS-CoV-2 colonization in BAL despite negative PCR results of nasal wash samples. His condition improved with 14 days of antibiotics. He was stable at his last follow-up. DISCUSSION: Both patients had an initial episode of mild COVID-19 pneumonitis, appropriate seroconversion, and prolonged viral colonization in the respiratory tract. Immunosuppression may have predisposed to rhinovirus and PsA superinfection in case 1 and 2, respectively. CONCLUSIONS: A high index of suspicion for superimposed infections in LTRs recovering from COVID-19 is warranted. Reference #1: 1. Hogan JI, Kotton CN. A Call for Caution in the Immunocompromised: Coronavirus Disease 2019 Associated With Mortality in a Vaccinated Lung Transplant Recipient. Open Forum Infect Dis. 2021 Nov 10;8(12):ofab557. DISCLOSURES: No relevant relationships by Hesham Abdelrazek No relevant relationships by Ashwini Arjuna No relevant relationships by Bhuvin Buddhdev No relevant relationships by Deepika Razia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia No relevant relationships by Rajat Walia, value=Honoraria Removed 04/04/2022 by Rajat Walia

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