Fulminant myocarditis following SARS-CoV-2 mRNA vaccination rescued with venoarterial ECMO: A report of two cases

Objectives: Cases of fulminant myocarditis after mRNA COVID-19 vaccination have been reported. The most severe may need venoarterial extracorporeal membrane oxygenation (V-A ECMO) support. Here we report two cases successfully rescued with V-A ECMO. Method(s): We included all the cases supported with V-A ECMO for refractory cardiogenic shock due to myocarditis secondary to a mRNA SARS-COV2 vaccine in the high-volume adult ECMO Program in Vall Hebron University Hospital since January 2020. Result(s): We identified two cases (table). One of them was admitted for out-of-hospital cardiac arrest. In both, a peripheral V-A ECMO was implanted in the cath lab. An intra-aortic balloon pump was needed in one case for left ventricle unloading. Support could be successfully withdrawn in a mean of five days. No major bleeding or thrombosis complications occurred. Definite microscopic diagnosis could be reached in one case (Image, 3). Treatment was the same, using 1000mg of methylprednisolone/day for 3 days. A cardiac magnetic resonance 10 days after admission showed a significant improvement in systolic function and diffuse oedema and subepicardial contrast intake in different segments (Image, 1-2). Both patients were discharged fully recovered. Conclusion(s): V-A ECMO should be established in cases of COVID-19 vaccine-associated myocarditis with refractory cardiogenic shock during the acute phase. (Table Presented).

Anti-MDA5 and antisynthetase antibodies screening in severe SARS-CoV-2 pneumonia. be aware of false positive results

Background: Several reports have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may trigger a vigorous immune response that could lead to the appearance of various autoantibodies such as antinuclear antibodies, antiphospholipid antibodies or anti-neutrophil cytoplasmic antibodies, among others. Moreover, the pulmonary involvement in SARSCoV-2 may resemble that of patients with anti-MDA5 positive syndrome or acute form of antisynthetase syndrome. Objectives: Our aim was to analyse the presence of anti-MDA5 and other myositis-specific autoantibodies such as the antisynthetase antibodies in patients diagnosed with severe acute respiratory syndrome caused by SARS-CoV-2. Methods: Retrospective observational study performed in a tertiary care center. We included 28 patients admitted to the intensive care unit with severe acute respiratory syndrome, 14 at the onset of the disease (group A) and 14 after 30 days of being treated in an intensive care unit (group B). Chest CT was performed at the admission. We analyzed the presence of anti-MDA5 and antisynthetase antibodies by immunoblot (Euroimmune®) and in those who were positive we performed a confirmatory test by immunoprecipitation. Results: All chest CT showed bilateral ground glass pattern. Three out of 14 patients of group A (12 males, 86%, mean ± SD age 67.1 ± 12.2) were positive for antisynthetase antibodies (2 anti-PL7, 1 anti-Jo1), and 6 out of 14 patients of the group B (6 males, 48%, mean ± SD age 68.7 ± 8.1) were positive to antisynthetase antibodies (2 anti-PL7, 2 anti-PL-12, 1 anti-EJ, 1 anti-OJ+PL7). Immunoblots also show positivity for other myositis-specific or associated antibodies, such as anti-TIF1g, anti-PM75, anti-SAE and anti-SRP. All of these results found by immunoblotting were negative by immunoprecipitation. None of the 28 patients were positive for anti-MDA5 antibodies. Conclusion: Severe SARS-CoV-2 pneumonia is characterized by ground glass pattern in chest CT, as it is found in anti-MDA5 or antisynthetase syndrome. The positivity of several myositis related autoantibodies showed in immunoblot appears to be more related to the vigorous immune response producing polyclonal immunoglobulins than triggering a real myositis-associated interstitial lung disease. Clinicians must be aware about these false positive results in patients with severe COVID-19 acute respiratory syndrome.

Immunosuppressive treatment management in a cohort of hospitalised solid organ recipients affected by COVID-19

Background and importance Management of immunosuppression in recipients of solid organ transplantation (SOT) is challenging. Drugs used in COVID-19 involve drug-drug interactions (DDIs) with immunosuppressants. Aim and objectives To describe DDIs in hospitalised SOT recipients (SOTr) and to analyse DDI management and their clinical impact. Material and methods A retrospective single centre study was conducted in SOTr with COVID-19 hospitalised from 11 March to 25 April. Clinical data and pharmacotherapy were recorded from admission up to 28 days or discharge. Lexicomp was used to detect and categorise DDIs according to: risk level (X: avoid combination;D: consider therapy modification;C: monitor therapy;B: no action needed), reliability rating and severity. 46 patients were included: 33 (71.7%) men, aged 62.7 ±12.6 (mean±SD) years. They had received kidney (30;56.2%), lung (13;28.3%) or liver (3;6.5%) transplants. Results Immunosuppression at admission: tacrolimus (41;89.1%), mycophenolate mofetil/mycophenolate sodium (28;60.9%), prednisone (39;84.8%), everolimus (7;15.2%), sirolimus (7;15.2%) and cyclosporine (1;2.2%). 106 DDIs affecting 42 (91.3%) patients were detected (patients could have >1 DDI). DDIs were classified as confirmed (18;39.1%) or potential (33;71.7%). Immunosuppressants with DDIs: tacrolimus (65;61.3%), everolimus (12;11.3%), sirolimus (6;5.7%), methylprednisolone (12;11.3%), prednisone (10;9.4%) and mycophenolate (1;0.9%). Drugs for COVID-19 with DDIs: lopinavir/ritonavir (45;42.5%), azithromycin (32;30.2%), tocilizumab (15;14.2%), darunavir/cobicistat (10;9.4%), and hydroxychloroquine (4;3.8%). DDIs were risk X (6;5.6%), risk D (42;40.8%), risk C (57;53.7%) and risk B (1;0.9%). The reliability rate of DDIs was excellent (0.9%), good (52.8%) and fair (44.3%). Severity was low, moderate and major in 6.6%, 84.9% and 8.5% of cases, respectively. Immunosuppression was withheld in 33 (71.7%) patients due to DDIs. 36 (87.7%) of 41 patients receiving tacrolimus had 65 DDIs;tacrolimus was withdrawn in 22 (61.1%), reduced in 18 (50%) and increased in 4 (11.1%) cases. Seven patients receiving everolimus had 12 DDIs and 4 patients with sirolimus had 6 DDIs;immunosuppressant was stopped in all cases. Tacrolimus levels were supratherapeutic (>10 ng/mL) in 8 (25%) patients at admission, 13 (43.3%;n=30) at 48 hours, 10 (31.3%, n=32) at 7 days and 2 at 14 days (17.7%, n=28). No graft rejection was detected. Mean creatinine serum concentration was 2.2 mg/dL at admission and 2.6 mg/ dL 7 days later. Two cases of acute kidney failure were attributable to tacrolimus intoxication. Conclusion and relevance DDIs were highly prevalent in hospitalised SOTr with COVID-19. Pharmaceutical care is critical to promptly detect and manage DDIs in SOTr.

4CPS-317 Immunosuppressive treatment management in a cohort of hospitalised solid organ recipients affected by COVID-19

Background and importanceManagement of immunosuppression in recipients of solid organ transplantation (SOT) is challenging. Drugs used in COVID-19 involve drug–drug interactions (DDIs) with immunosuppressants.Aim and objectivesTo describe DDIs in hospitalised SOT recipients (SOTr) and to analyse DDI management and their clinical impact.Material and methodsA retrospective single centre study was conducted in SOTr with COVID-19 hospitalised from 11 March to 25 April. Clinical data and pharmacotherapy were recorded from admission up to 28 days or discharge. Lexicomp was used to detect and categorise DDIs according to: risk level (X: avoid combination;D: consider therapy modification;C: monitor therapy;B: no action needed), reliability rating and severity. 46 patients were included: 33 (71.7%) men, aged 62.7±12.6 (mean±SD) years. They had received kidney (30;56.2%), lung (13;28.3%) or liver (3;6.5%) transplants.ResultsImmunosuppression at admission: tacrolimus (41;89.1%), mycophenolate mofetil/mycophenolate sodium (28;60.9%), prednisone (39;84.8%), everolimus (7;15.2%), sirolimus (7;15.2%) and cyclosporine (1;2.2%). 106 DDIs affecting 42 (91.3%) patients were detected (patients could have >1 DDI). DDIs were classified as confirmed (18;39.1%) or potential (33;71.7%). Immunosuppressants with DDIs: tacrolimus (65;61.3%), everolimus (12;11.3%), sirolimus (6;5.7%), methylprednisolone (12;11.3%), prednisone (10;9.4%) and mycophenolate (1;0.9%).Drugs for COVID-19 with DDIs: lopinavir/ritonavir (45;42.5%), azithromycin (32;30.2%), tocilizumab (15;14.2%), darunavir/cobicistat (10;9.4%), and hydroxychloroquine (4;3.8%). DDIs were risk X (6;5.6%), risk D (42;40.8%), risk C (57;53.7%) and risk B (1;0.9%). The reliability rate of DDIs was excellent (0.9%), good (52.8%) and fair (44.3%). Severity was low, moderate and major in 6.6%, 84.9% and 8.5% of cases, respectively.Immunosuppression was withheld in 33 (71.7%) patients due to DDIs. 36 (87.7%) of 41 patients receiving tacrolimus had 65 DDIs;tacrolimus was withdrawn in 22 (61.1%), reduced in 18 (50%) and increased in 4 (11.1%) cases. Seven patients receiving everolimus had 12 DDIs and 4 patients with sirolimus had 6 DDIs;immunosuppressant was stopped in all cases. Tacrolimus levels were supratherapeutic (>10 ng/mL) in 8 (25%) patients at admission, 13 (43.3%;n=30) at 48 hours, 10 (31.3%, n=32) at 7 days and 2 at 14 days (17.7%, n=28). No graft rejection was detected. Mean creatinine serum concentration was 2.2 mg/dL at admission and 2.6 mg/dL 7 days later. Two cases of acute kidney failure were attributable to tacrolimus intoxication.Conclusion and relevanceDDIs were highly prevalent in hospitalised SOTr with COVID-19. Pharmaceutical care is critical to promptly detect and manage DDIs in SOTr.References and/or acknowledgementsThanks to the COVID-19 Vall d’Hebron Working GroupConflict of interestNo conflict of interest