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1.
Am J Transplant ; 21(12): 3817-3818, 2021 12.
Article in English | MEDLINE | ID: covidwho-2192286
2.
CMAJ ; 194(46): E1578-E1586, 2022 Nov 28.
Article in French | MEDLINE | ID: covidwho-2197233

ABSTRACT

CONTEXTE: La forme grave de COVID-19 semble affecter de manière disproportionnée les gens immunovulnérables, même si les données canadiennes dans ce contexte sont limitées. Nous avons voulu déterminer quels facteurs sont associés aux paramètres de la forme grave de COVID-19 chez les receveurs de transplantations au Canada. MÉTHODES: Nous avons procédé à une étude de cohorte multicentrique prospective regroupant tous les receveurs d'une transplantation d'organe plein ayant reçu un diagnostic de COVID-19 suivis dans 9 programmes de transplantation au Canada entre mars 2020 et novembre 2021. Les données ont été analysées afin de dégager les facteurs de risque à l'égard du recours à l'oxygénothérapie et autres critères de la gravité de la maladie. Nous avons comparé les paramètres selon le type d'organe transplanté et suivi l'évolution des paramètres au fil du temps. Nous avons procédé à une analyse multivariée pour déterminer quelles variables sont associées au recours à l'oxygénothérapie. RÉSULTATS: En tout, 509 patients ayant reçu une transplantation d'organe plein ont contracté la COVID-19 durant la période de l'étude. Les facteurs de risque associés au recours à l'oxygénothérapie (n = 190) ou non (n = 319) incluaient l'âge (âge médian 62,6 ans, intervalle interquartile [II] 52,5­69,5 ans c. âge médian 55,5 ans, II 47,5­66,5; p < 0,001) et le nombre de comorbidités (nombre médian 3, II 2­3 c. nombre médian 2, II 1­3; p < 0,001), de même que les paramètres concernant l'immunosuppression. Les receveurs d'une transplantation pulmonaire (n = 48) étaient plus susceptibles de souffrir d'une forme grave de la maladie, avec un taux de mortalité élevé (n = 15, 31,3 %) comparativement aux receveurs d'autres organes, y compris le rein (n = 48, 14,8 %), le cœur (n = 1, 4,4 %), le foie (n = 9, 11,4 %) et le rein­pancréas (n = 3, 12,0 %) (p = 0,02). Les facteurs protecteurs contre le recours à l'oxygénothérapie incluaient le fait d'avoir subi une transplantation hépatique et de recevoir de l'azathioprine. Le fait d'avoir reçu 2 doses de vaccin anti-SRAS-CoV-2 n'a pas eu d'influence appréciable sur le recours à l'oxygénothérapie. L'analyse multivariée a montré que l'âge avancé (rapport des cotes [RC] 1,04, intervalle de confiance [IC] de 95 % 1,02­1,07) et le nombre de comorbidités (RC 1,63, IC de 95 % 1,30­2,04), entre autres facteurs, étaient associés au recours à l'oxygénothérapie. La gravité de la maladie n'a pas considérablement diminué au fil du temps. INTERPRÉTATION : Malgré les progrès thérapeutiques et la vaccination des receveurs d'une transplantation d'organe plein, les signes de gravité accrue de la COVID-19, en particulier chez les receveurs d'une transplantation pulmonaire, justifient le maintien des mesures de santé publique pour protéger ces personnes à risque, et l'utilisation hâtive de traitements contre la COVID-19 chez les receveurs d'une transplantation d'organe plein.


Subject(s)
COVID-19 , Organ Transplantation , Humans , Prospective Studies , Transplant Recipients , Canada
3.
Ther Drug Monit ; 42(3): 360-368, 2020 06.
Article in English | MEDLINE | ID: covidwho-2152206

ABSTRACT

BACKGROUND: COVID-19 is a novel infectious disease caused by the severe acute respiratory distress (SARS)-coronavirus-2 (SARS-CoV-2). Several therapeutic options are currently emerging but none with universal consensus or proven efficacy. Solid organ transplant recipients are perceived to be at increased risk of severe COVID-19 because of their immunosuppressed conditions due to chronic use of immunosuppressive drugs (ISDs). It is therefore likely that solid organ transplant recipients will be treated with these experimental antivirals. METHODS: This article is not intended to provide a systematic literature review on investigational treatments tested against COVID-19; rather, the authors aim to provide recommendations for therapeutic drug monitoring of ISDs in transplant recipients infected with SARS-CoV-2 based on a review of existing data in the literature. RESULTS: Management of drug-drug interactions between investigational anti-SARS-CoV-2 drugs and immunosuppressants is a complex task for the clinician. Adequate immunosuppression is necessary to prevent graft rejection while, if critically ill, the patient may benefit from pharmacotherapeutic interventions directed at limiting SARS-CoV-2 viral replication. Maintaining ISD concentrations within the desired therapeutic range requires a highly individualized approach that is complicated by the pandemic context and lack of hindsight. CONCLUSIONS: With this article, the authors inform the clinician about the potential interactions of experimental COVID-19 treatments with ISDs used in transplantation. Recommendations regarding therapeutic drug monitoring and dose adjustments in the context of COVID-19 are provided.


Subject(s)
Antiviral Agents/adverse effects , Coronavirus Infections/drug therapy , Drug Monitoring , Immunosuppressive Agents/adverse effects , Pneumonia, Viral/drug therapy , Transplant Recipients , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antibodies, Monoclonal, Humanized , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Drug Interactions , Glucocorticoids , Humans , Hydroxychloroquine , Immunosuppressive Agents/therapeutic use , Pandemics , Protease Inhibitors , SARS-CoV-2
4.
Transpl Int ; 35: 10721, 2022.
Article in English | MEDLINE | ID: covidwho-2154859

ABSTRACT

Kidney transplant recipients (KTR) are at increased risk for COVID-19-associated complications. We aimed to describe the evolving epidemiology and outcome of PCR-documented SARS-CoV-2 infection in KTR followed at our institution from March 2020 to May 2022. The primary endpoint was hospitalization for COVID-19-related symptoms or death within 28 days from diagnosis. Overall, 243 cases were included of which 68 (28%) developed the primary outcome. A significant decrease in the incidence of the primary outcome was observed (p < 0.001, r -0.342) during the study period. Anti-Spike monoclonal antibodies (mAbs) were administered as early treatment (within 5-7 days of onset of symptoms) in 101 patients (14 with casirivimab/imdevimab and 87 with sotrovimab). Among 145 patients who had received at least one vaccination dose before infection, 109 patients were considered as adequately vaccinated. Multivariate analysis revealed that the Charlson Comorbidity Index (P 0.001; OR 1.28, CI 1.11-1.48) was associated with the primary outcome, while early administration of mAbs (P 0.032; OR 0.39, CI 0.16-0.92) was associated with a better outcome, but not infection during the period of the omicron variant predominance or adequate vaccination.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Transplant Recipients
5.
Eur Respir J ; 60(5)2022 11.
Article in English | MEDLINE | ID: covidwho-2139117

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) social distancing measures led to a dramatic decline in non-COVID-19 respiratory virus infections, providing a unique opportunity to study their impact on annual forced expiratory volume in 1 s (FEV1) decline, episodes of temporary drop in lung function (TDLF) suggestive of infection and chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). METHODS: All FEV1 values of LTRs transplanted between 2009 and April 2020 at the University Medical Center Groningen (Groningen, The Netherlands) were included. Annual FEV1 change was estimated with separate estimates for pre-social distancing (2009-2020) and the year with social distancing measures (2020-2021). Patients were grouped by individual TDLF frequency (frequent/infrequent). Respiratory virus circulation was derived from weekly hospital-wide respiratory virus infection rates. Effect modification by TDLF frequency and respiratory virus circulation was assessed. CLAD and TDLF rates were analysed over time. RESULTS: 479 LTRs (12 775 FEV1 values) were included. Pre-social distancing annual change in FEV1 was -114 (95% CI -133- -94) mL, while during social distancing FEV1 did not decline: 5 (95% CI -38-48) mL (difference pre-social distancing versus during social distancing: p<0.001). The frequent TDLF subgroup showed faster annual FEV1 decline compared with the infrequent TDLF subgroup (-150 (95% CI -181- -120) versus -90 (95% CI -115- -65) mL; p=0.003). During social distancing, we found significantly lower odds for any TDLF (OR 0.53, 95% CI 0.33-0.85; p=0.008) and severe TDLF (OR 0.34, 0.16-0.71; p=0.005) as well as lower CLAD incidence (OR 0.53, 95% CI 0.27-1.02; p=0.060). Effect modification by respiratory virus circulation indicated a significant association between TDLF/CLAD and respiratory viruses. CONCLUSIONS: During COVID-19 social distancing the strong reduction in respiratory virus circulation coincided with markedly less FEV1 decline, fewer episodes of TDLF and possibly less CLAD. Effect modification by respiratory virus circulation suggests an important role for respiratory viruses in lung function decline in LTRs.


Subject(s)
COVID-19 , Lung Transplantation , Viruses , Humans , Transplant Recipients , Physical Distancing , Follow-Up Studies , Lung
6.
Transplantation ; 105(1): 177-186, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-2135857

ABSTRACT

BACKGROUND: A concern about the susceptibility of immunocompromised patients to the worldwide pandemic of coronavirus disease 2019 (COVID-19) has been raised. We aimed at describing COVID-19 infections in the French cohort of lung transplant (LT) patients. METHODS: Multicenter nationwide cohort study of all LT recipients with COVID-19 diagnosed from March 1 to May 19, 2020. Recipient main characteristics and their management were retrieved. Hospitalization characteristics, occurrence of complications and survival were analyzed. RESULTS: Thirty-five LT patients with a COVID-19 infection were included. Median age was 50.4 (40.6-62.9) years, 16 (45.7%) were female, and 80% were double-LT recipients. Infection was community-acquired in 25 (71.4%). Thirty-one (88.6%) required hospitalization, including 13 (41.9%) in the intensive care unit. The main symptoms of COVID-19 were fever, cough, and diarrhea, present in 71.4%, 54.3%, and 31.4% of cases, respectively. Extension of pneumonia on chest CT was moderate to severe in 51.4% of cases. Among the 13 critically ill patients, 7 (53.9%) received invasive mechanical ventilation. Thrombotic events occurred in 4 patients. Overall survival rate was 85.7% after a median follow-up of 50 days (41.0-56.5). Four of 5 nonsurvivors had had bronchial complications or intensification of immunosuppression in the previous weeks. On univariate analysis, overweight was significantly associated with risk of death (odds ratio, 16.0; 95% confidence interval, 1.5-170.6; P = 0.02). CONCLUSIONS: For the 35 LT recipients with COVID-19, the presentation was severe, requiring hospitalization in most cases, with a survival rate of 85.7%.


Subject(s)
COVID-19/complications , Lung Transplantation/adverse effects , SARS-CoV-2 , Adult , COVID-19/mortality , COVID-19/therapy , Female , Humans , Immunosuppressive Agents/therapeutic use , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Transplant Recipients
8.
Transplantation ; 106(12): 2399-2407, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2135880

ABSTRACT

BACKGROUND: The COVID-19 pandemic is the first sustained respiratory disease pandemic to arise since the start of solid organ transplantation (SOT). Prior studies have demonstrated that SOT recipients are at greater risk for severe complications of infection and are less likely to respond to vaccination. METHODS: The Scientific Registry of Transplant Recipients Standard Analysis Files was used to assess the cumulative excess mortality in SOT recipients during the first 20 mo of the pandemic. RESULTS: Compared with excess mortality rates in the US population (25.9 deaths/10 000; confidence interval [CI], 10.9-41.1), the excess mortality per 10 000 was higher in all SOT groups: kidney (188.5; CI, 150.7-225.6), lung (173.6; CI, 17-334.7), heart (123.7; CI, 56-191.4), and liver (105.1; CI, 64.6-146). The higher rates persisted even with attempts to control for population age structure and renal allograft failure. Excess mortality was also higher in Black (236.8; CI, 186.1-287) and Hispanic (256.9; CI, 208.1-305.2) organ recipients compared with other racial and ethnic groups in the Scientific Registry of Transplant Recipients and compared with the Black and Hispanic populations in the United States. CONCLUSIONS: Studies of excess mortality provide insight into the health and survival of specialized populations like SOT recipients during major health events like the COVID-19 pandemic.


Subject(s)
COVID-19 , Kidney Transplantation , Organ Transplantation , United States/epidemiology , Humans , Transplant Recipients , Pandemics , Kidney Transplantation/adverse effects , Organ Transplantation/adverse effects
9.
Curr Opin Organ Transplant ; 27(4): 269-276, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-2118071

ABSTRACT

PURPOSE OF REVIEW: Coronavirus disease-2019 (COVID-19) disproportionately causes severe outcomes in solid organ transplant recipients (SOTR). Antispike monoclonal antibodies have been authorized for therapy and prophylaxis for COVID-19. Here, we review the current state of antispike monoclonal antibodies and their role for SOTRs. RECENT FINDINGS: Bamlanivimab with or without etesevimab, casirivimab-imdevimab and sotrovimab have reduced the rates of hospitalization and severe disease in high-risk patients with mild-to-moderate COVID-19. Multiple retrospective studies have also demonstrated monoclonal antibodies are effective in SOTR populations. However, the evolution of resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concerns has resulted in revocation of the authorization of bamlanivimab with or without etesevimab, and casirivimab-imdevimab as treatment and postexposure prophylaxis (PEP). Sotrovimab and bebtelovimab are currently authorized for treatment of the predominant circulating SARS-CoV-2 B.1.1.529 (Omicron), but not as pre or PEP. Tixagevimab-cilgavimab, a long-acting antibody combination preparation, is authorized for preexposure prophylaxis in high-risk immunocompromised populations, including SOTRs, who are less likely to mount an effective immune response following vaccination series and booster. SUMMARY: Antispike monoclonal antibodies are useful for the prevention and treatment of mild-to-moderate COVID-19 in SOTRs. However, their clinical use should be determined by the evolving epidemiology of SARS-CoV-2 variants in the community.


Subject(s)
COVID-19 , Organ Transplantation , Humans , SARS-CoV-2 , COVID-19/prevention & control , Retrospective Studies , Antibodies, Monoclonal/adverse effects , Organ Transplantation/adverse effects , Transplant Recipients
12.
PLoS One ; 17(11): e0276929, 2022.
Article in English | MEDLINE | ID: covidwho-2098767

ABSTRACT

Mortality due to COVID-19 is not increased in immunosuppressed individuals after liver transplantation (OLT) compared to individuals without immunosuppression. Data on long-term protective immunity against SARS-CoV-2 in immunosuppressed convalescents, is limited. We prospectively measured immune responses against SARS-CoV-2 by quantifying antibodies against 4 different antigens (spike protein 1 and 2, receptor binding domain, nucleocapsid) and T cell responses by IFN-γ ELISPOT against 4 antigens (membrane, nucleocapsid, spike protein 1 and 2) in 24 OLT convalescents with immunosuppressive therapy longitudinally in the first year after COVID-19 including a booster vaccination in comparison to a matched cohort of non-immunosuppressed convalescents (non-IS-Con). Pre-pandemic OLT samples were retrieved from our prospective OLT biorepository (n = 16). No relevant T cell reactivity or immunoglobulin G (IgG) against SARS-CoV-2 were detectable in pre-pandemic samples of OLT recipients despite reactivity against endemic corona-viruses. OLT convalescents had a lower prevalence of IgG against nucleocapsid (54% vs. 90%) but not against spike protein domains (98-100% vs. 100%) after vaccination in the second half-year after COVID-19 compared to non-IS-Con. Also, concentrations of anti-nucleocapsid IgG were lower in OLT convalescents than in non-IS-Con. Concentration of IgG against spike protein domains was significantly increased by a booster vaccination in OLT convalescents. But concentration of IgG against two of three spike protein domains remains slightly lower compared to non-IS-Con finally. However, none of these differences was mirrored by the cellular immunity against SARS-CoV-2 that remained stable during the first year after COVID-19 and was not further stimulated by a corona vaccination in OLT convalescents. In conclusion, despite lower concentrations of anti-SARS-CoV-2 IgG in OLT convalescents anti-SARS-CoV-2 cellular immunity was as robust as in non-IS-Con.


Subject(s)
COVID-19 , Liver Transplantation , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Prospective Studies , Antibodies, Viral , Immunoglobulin G , Immunity, Cellular , Immunity, Humoral , Vaccination , Transplant Recipients
13.
Exp Clin Transplant ; 20(Suppl 1): 156-160, 2022 03.
Article in English | MEDLINE | ID: covidwho-2090786

ABSTRACT

OBJECTIVES: The new coronavirus SARS-CoV-2 (COVID-19) first appeared in Turkey in March 2020, spread rapidly, and caused many deaths. Although COVID-19 is mostly a respiratory disease, it can cause kidney and multiorgan failure in some cases. We believe that by sharing information about the course and effects of COVID-19 infection in kidney transplant recipients receiving long-term immunosuppressive therapy our understanding will improve. MATERIALS AND METHODS: Between March 2020 and October 2021, COVID-19 was researched in kidney transplant recipients under the age of 20 years who were followed at the Baskent University Transplantation Center. We documented the clinical characteristics and prognosis of pediatric kidney transplant recipients with COVID-19 disease. RESULTS: Our study group included 23 patients with COVID-19 infection from 215 pediatric kidney transplant recipients. The mean age of the patients was 14.6 ± 4.7 years; there were 9 female patients. The mean follow-up time posttransplant was 62.3 ± 43.2 months. In 13 patients (56.5%), fever was the most frequent symptom. Most patients (n = 18, 78%) had minor symptoms and recovered completely after receiving supportive treatment. Four patients (17%) required hospitalization. One was diagnosed with COVID-19 infection 1 week after being treated with rituximab for acute antibody-mediated rejection. That patient died because of significant lung disease and multiorgan failure. CONCLUSIONS: Despite the fact that most of our pediatric transplant recipients had mild symptoms of COVID-19, we believe that particular caution should be observed in patients who have recently received intensive immunosuppressive medications. As a result of potential new vaccines, national immunization programs, and the emergence of novel virus strains, the clinical picture may change in the future. We believe that, as information sharing increases, we will learn more about COVID-19 in renal transplant recipients.


Subject(s)
COVID-19 , Kidney Transplantation , Adolescent , Adult , Child , Female , Humans , Kidney , Kidney Transplantation/adverse effects , SARS-CoV-2 , Transplant Recipients , Treatment Outcome , Young Adult
14.
Viruses ; 14(11)2022 Oct 30.
Article in English | MEDLINE | ID: covidwho-2090371

ABSTRACT

BACKGROUND: COVID-19 severity is determined by cardiometabolic risk factors, which can be further aggravated by chronic immunosuppression in kidney transplant recipients (KTRs). We aimed to verify the main risk factors related to hypertension (HTN) that contribute to COVID-19 progression and mortality in that population. METHODS: Retrospective analysis of 300 KTRs from March 2020 to August 2020 in a single center. We compared the main outcomes between HTN (n = 225) and non-HTN (n = 75), including admission to the intensive care unit (ICU), development of acute kidney injury (AKI), need for invasive mechanical ventilation or oxygen, and mortality. RESULTS: Of the patients in the study, 57.3% were male, 61.3% were white, the mean age was 52.5 years, and 75% had HTN. Pre-existing HTN was independently associated with higher rates of mortality (32.9%, OR = 1.96, p = 0.036), transfer to the ICU (50.7%, OR = 1.94, p = 0.017), and AKI with hemodialysis (HD) requirement (40.4%, OR = 2.15, p = 0.011). In the hypertensive group, age, diabetes mellitus, heart disease, smoking, glycemic control before admission, C-reactive protein, lactate dehydrogenase, lymphocytes, and D-dimer were significantly associated with COVID-19 progression and mortality. Both lower basal and previous estimated glomerular filtration rates posed KTRs with HTN at greater risk for HD requirement. CONCLUSIONS: Therefore, the early identification of factors that predict COVID-19 progression and mortality in KTRs affected by COVID-19 contributes to therapeutic decisions, patient flow management, and allocation of resources.


Subject(s)
Acute Kidney Injury , COVID-19 , Hypertension , Kidney Transplantation , Humans , Male , Middle Aged , Female , Kidney Transplantation/adverse effects , Retrospective Studies , Transplant Recipients , Hypertension/epidemiology , Hypertension/etiology , Risk Factors , Cohort Studies
15.
Vaccine ; 40(48): 6971-6978, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2082750

ABSTRACT

BACKGROUND AND AIMS: Recent studies have reported poor humoral immune response to mRNA vaccines in patients with chronic liver disease (CLD). However, the immunogenicity of ChAdOx1 (vector-based) and BBV152 (inactivated virus) vaccines in patients with CLD and liver transplant recipients (LTRs) is unknown. Therefore, we aimed to assess the immunogenicity of ChAdOx1 and BBV152 vaccines in patients with CLD (including cirrhosis patients) and LTRs. METHODS: In this single-center prospective study, consecutive completely vaccinated (ChAdOx1 or BBV152) non-cirrhosis CLD patients, those with cirrhosis, and LTRs were compared with matched healthy controls for anti-spike antibody and cellular response. RESULTS: Sixty healthy individuals, 50 NCCLD patients, 63 compensated and 50 decompensated cirrhosis, and 17 LTRs were included. The proportion of non-responders was similar among the healthy control (8 %), non-cirrhosis CLD (16 %), and compensated cirrhosis groups (17.5 %;p = 0.3). However, a higher proportion of patients with decompensated cirrhosis (34 %) and LTRs (59 %) were non-responders than the healthy controls (p = 0.001). Cluster of differentiation (CD) 4-effector cells were lower in patients with non-cirrhosis CLD and compensated cirrhosis. CD4-naïve, CD4-effector, B, and B-memory cells were lower in the decompensated cirrhosis group. Although the central memory cells were higher in the decompensated cirrhosis group, they could not differentiate into effector cells. CD4- and CD8-naïve cells were higher in the marrow in the LTRs, while the CD4-effector memory cells and CD4- and CD8-effector cells were lower in the LTRs. Furthermore, B cells were more deficient in the LTRs, suggesting poor antibody response. CONCLUSION: Patients with decompensated cirrhosis and LTRs demonstrated suboptimal humoral and cellular immune responses against recombinant and inactivated COVID-19 vaccines.


Subject(s)
COVID-19 , Coronavirus , Liver Diseases , Liver Transplantation , Humans , COVID-19 Vaccines , Prospective Studies , Liver Cirrhosis , Immunity , Transplant Recipients
16.
Viruses ; 14(10)2022 10 19.
Article in English | MEDLINE | ID: covidwho-2081879

ABSTRACT

Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants of concern has highlighted the need to improve vaccine-induced immune responses by the administration of repeated booster doses. In this study, we analyzed the humoral and cellular responses in a cohort of 25 SOTRs, including 15 never-infected SOTRs who received the fourth dose of the mRNA vaccine and 10 SOTRs who contracted SARS-CoV-2 infection after the third dose. We analyzed the serum IgG and IgA levels through CLIA or ELISA, respectively, and the Spike-specific T cells by ELISpot assay. We report a significant increase in anti-Spike IgG and no differences in IgA secretion in both groups of patients before and after the booster dose or the natural infection. Still, we show higher IgA levels in recovered SOTRs compared to the fourth dose recipients. Conversely, we show the maintenance of a positive Spike-specific T-cell response in SOTRs who received the fourth dose, which, instead, was significantly increased in SOTRs who contracted the infection. Our results suggest that the booster, either through the fourth dose or natural infection, in vulnerable poor responder SOTRs, improves both humoral and cellular-specific immune responses against SARS-CoV-2.


Subject(s)
COVID-19 Vaccines , COVID-19 , Transplant Recipients , Humans , Antibodies, Viral , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Immunity , Immunoglobulin A , Immunoglobulin G , Organ Transplantation/adverse effects , SARS-CoV-2
17.
Exp Clin Transplant ; 20(Suppl 4): 74-79, 2022 08.
Article in English | MEDLINE | ID: covidwho-2080822

ABSTRACT

OBJECTIVES: The COVID-19 pandemic has hit the world in an almost unprecedented way. Patients with endstage chronic renal failure, who are on hemodialysis, with glomerulonephritis and complicated pyelonephritis and other nephrological diseases, were under constant close supervision of specialists, despite the existing difficulties for face-to-face contact between the patient and the doctor at our hospital in Tashkent, Uzbekistan, where primary detection and treatment of these patients were also actively conducted. Here, we report the features of the course of treatment for COVID-19 infection in patients who underwent kidney transplant living related donors during the global pandemic in Uzbekistan. MATERIALS AND METHODS: After a decree from the Cabinet of Ministers of the Republic of Uzbekistan in October 2017 for approval and regulations for related kidney and (or) liver lobe procedures, our center performed 609 kidney transplants from living related donors between 2017 and 2022, with 320 procedures during the pandemic. There were 228 transplant recipients with COVID-19 infections and COVID-19-associated pneumonia. RESULTS: Of total cases with COVID-19, 71% had moderate disease severity. Of patients who under went kidney transplant, 42% had pneumonia associated with COVID-19 infection. After lung damage was confirmed by multislice computed tomography of the lungs, patients were sent to the intensive care unit for appropriate treatment to ensure a quick recovery without possible complications to the graft. CONCLUSIONS: The Ministry of Health of the Republic of Uzbekistan indicated the possibility of treatment of patients with moderate and severe COVID-19 disease with monoclonal antibodies that block interleukin 6 receptors (tocilizumab and sarilumab). With timely detection of symptoms of COVID-19infection, treatment, and the use of prevention methods, kidney transplant recipients of living related donors had fewer complications of the disease than expected.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , Incidence , Pandemics , SARS-CoV-2 , Transplant Recipients , Treatment Outcome , Uzbekistan
18.
BMJ Open ; 12(7): e060425, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-2078972

ABSTRACT

OBJECTIVES: To determine whether spontaneous reporting rates of myocarditis and pericarditis differed in immunocompromised patients compared with the whole population overall, and in terms of demographics, vaccine dose and time-to-onset. DESIGN: Systematic review of spontaneously reported data from the European Union/European Economic Area (EU/EEA), the USA and the UK. DATA SOURCES: EudraVigilance (EU/EEA), Vaccine Adverse Event Reporting System (VAERS; USA) and the Medicines and Healthcare products Regulatory Agency (UK) spontaneous reporting databases were searched from date of vaccine launch to 1 December 2021. ELIGIBILITY CRITERIA: Publicly available spontaneous reporting data for 'myocarditis' and 'pericarditis' from EU/EEA and USA following COVID-19 messenger RNA vaccines. Reports with comorbidities or concurrent medication indicative of transplantation, HIV infection or cancer ('immunocompromised' population) were compared with each overall database population. DATA EXTRACTION AND SYNTHESIS: Two researchers extracted data. Spontaneously reported events of myocarditis and pericarditis were presented for immunocompromised populations for each data source, stratified by age, sex, dose and time-to-onset (where available). Seriousness of each event was determined according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guideline E2A definition. Proportional reporting ratio (PRR) was calculated. RESULTS: There were 178 reports of myocarditis and pericarditis among immunocompromised individuals overall. Seriousness was comparable between the immunocompromised and overall populations in both databases. No trends in age or sex were observed among immunocompromised individuals. Most reports followed a second vaccine dose and occurred within 14 days. The frequency of reporting was similar to the wider population (PRR=1.36 (95% CI=0.89 to 1.82) for VAERS population). CONCLUSIONS: Myocarditis and pericarditis following COVID-19 vaccination are very rare, and benefits of COVID-19 vaccination continue to outweigh any perceived risks. Reporting rates of myocarditis and pericarditis were similar in immunocompromised individuals, however defining characteristics differed compared with the whole population; therefore, continued monitoring of adverse events following vaccination remains vital to understand differences between population subgroups.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunocompromised Host , Myocarditis/epidemiology , Pericarditis/epidemiology , Transplant Recipients
19.
Viruses ; 14(10)2022 10 09.
Article in English | MEDLINE | ID: covidwho-2071830

ABSTRACT

BACKGROUND: Molnupiravir demonstrated an in vitro antiviral activity against positive-sense RNA viruses, including SARS-CoV-2. The study aimed to present the results of outpatient molnupiravir use in kidney transplant recipients and hemodialysis patients during the first months of 2022 in Poland. METHODS: The retrospective observational cohort study at one kidney transplant center included 36 patients diagnosed with COVID-19 with an automated nucleic acid amplification test on nasopharyngeal swab specimens. All patients received molnupiravir for home-based therapy at a dose of 800 mg every 12 h orally for 5 days. Both kidney transplant recipients (n = 16) and hemodialysis patients (n = 20) presented a lot of comorbidities with a Charlson comorbidity index of 4.1 and 5.1, respectively. RESULTS: Patients presented with fever, cough, and weakness followed by muscle and joint pain. Five kidney transplant recipients experienced acute kidney injury with a rise in serum creatinine level from 0.4 to 1.9 mg/dL. No serious side effects of molnupiravir therapy or interactions with immunosuppressive medications were observed. Symptoms of COVID-19 improved rapidly or resolved within 24-48 h of starting treatment. CONCLUSION: The study suggests the safety and efficacy of molnupiravir therapy alone early after the onset of SARS-CoV-2 infection, but further investigations should be performed to confirm our preliminary results. To the best of the authors' knowledge, it is the first published report on molnupiravir use in end-stage kidney disease (ESKD) patients on hemodialysis and the third concerning kidney transplant recipients.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , COVID-19/therapy , SARS-CoV-2 , Kidney Transplantation/adverse effects , Retrospective Studies , Outpatients , Creatinine , Transplant Recipients , Antiviral Agents/therapeutic use
20.
Int J Mol Sci ; 23(20)2022 Oct 15.
Article in English | MEDLINE | ID: covidwho-2071512

ABSTRACT

The vulnerable population of kidney transplant recipients (KTRs) are low responders to COVID-19 vaccines, so specific immune surveillance is needed. The interferon-gamma (IFN-γ) release assay (IGRA) is effective in assessing T cell-mediated immunity. We assessed SARS-CoV-2-directed T cell responses in KTRs with absent antibody production after a third dose of the mRNA-1273 vaccine, using two different IGRAs. A cohort of 57 KTRs, who were actively followed up, received a third dose of the mRNA-1273 vaccine. After the evaluation of humoral immunity to SARS-CoV-2, 14 seronegative patients were tested with two commercial IGRAs (SD Biosensor and Euroimmun). Out of 14 patients, one and three samples were positive by IGRAs with Euroimmun and SD Biosensor, respectively. The overall agreement between the two assays was 85.7% (κ = 0.444). In addition, multivariate linear regression analysis showed no statistically significant association between the IFN-γ concentration, and the independent variables analyzed (age, gender, years since transplant, total lymphocytes cells/mcl, CD3+ cells/mcl, CD3+ CD4+ cells/mcl, CD3+ CD8+ cells/mcl, CD19+ cells/mcl, CD3-CD16+CD56+ cells/mcl) (p > 0.01). In a vulnerable setting, assessing cellular immune response to complement the humoral response may be advantageous. Since the two commercial IGRAs showed a good agreement on negative samples, the three discordant samples highlight the need for further investigations.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , 2019-nCoV Vaccine mRNA-1273 , Interferon-gamma/analysis , T-Lymphocytes/chemistry , COVID-19 Vaccines , Antibody Formation , SARS-CoV-2 , COVID-19/prevention & control , Transplant Recipients , Antibodies, Viral
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