Antibody Response After Third Vaccination With mRNA-1273 or BNT162b2: Extension of a Randomized Controlled SARS-CoV-2 Noninferiority Vaccine Trial in Patients With Different Levels of Immunosuppression (COVERALL-2).

Extension of the COVERALL (COrona VaccinE tRiAL pLatform) randomized trial showed noninferiority in antibody response of the third dose of Moderna mRNA-1273 vaccine (95.3% [95% confidence interval {CI}, 91.9%-98.7%]) compared to Pfizer-BioNTech BNT162b2 vaccine (98.1% [95% CI, 95.9%-100.0%]) in individuals with different levels of immunosuppression (difference, -2.8% [95% CI, -6.8% to 1.3%]).

Aminoadamantanes: from treatment of Parkinson's and Alzheimer's disease to symptom amelioration of long COVID-19 syndrome?

INTRODUCTION: The aminoadamantanes amantadine and memantine are well known. They mainly act as N-methyl-D-aspartate antagonists. AREAS COVERED: The antiviral drug amantadine moderately ameliorates impaired motor behavior in patients with Parkinson's disease. Memantine provides beneficial effects on memory function in patients with advanced Alzheimer's disease already treated with acetylcholine esterase inhibitors. Both compounds counteract impaired monoamine neurotransmission with associated symptoms, such as depression. They improve vigilance, lack of attention and concentration, fatigue syndromes according to clinical findings in patients with chronic neurodegenerative processes. Their extrasynaptic N-methyl-D-Aspartate receptor blockade weakens a prolonged influx of Ca2+ ions as the main responsible components of neuronal excitotoxicity. This causes neuronal dying and associated functional deficits. EXPERT OPINION: We suggest aminoadamantanes as future therapies for amelioration of short- and long-term consequences of a COVID 19 infection. Particularly the extended-release amantadine formulations will be suitable. They showed better clinical efficacy compared with the conventional available compounds. Amantadine may particularly be suitable for amelioration of fatigue or chronic exhaustion, memantine for improvement of cognitive deficits. Clinical research in patients, who are affected by the short- and long-term consequences of a COVID 19 infection, is warranted to confirm these still hypothetical putative beneficial effects of aminoadamantanes.

The drugs amantadine and memantine are known as aminoadamantanes. Amantadine improves motor skills in patients with Parkinson's disease. It also reduces fatigue in individuals suffering from multiple sclerosis. Memantine improves memory dysfunction linked to Alzheimer's disease. Aminoadamantanes affect communication between nerve cells by supporting neurotransmission of monoamines. Clinical studies have found that these drugs benefit patients with chronic neurodegenerative diseases, who have depression, fatigue, loss of attention or concentration deficits. These brain function problems may also appear to some extent due to COVID-19 infection. We suggest that aminoadamantanes could improve these problems in COVID-19 patients in both the short and long term. Clinical research is needed to confirm this hypothesis.

Prognostic factors for favorable outcomes after veno-venous extracorporeal membrane oxygenation in critical care patients with COVID-19.

BACKGROUND: Patients with COVID-19 and severe acute respiratory failure may require veno-venous extracorporeal membrane oxygenation (VV ECMO). Yet, this procedure is resource-intensive and high mortality rates have been reported. Thus, predictors for identifying patients who will benefit from VV ECMO would be helpful. METHODS: This retrospective study included 129 patients with COVID-19 and severe acute respiratory failure, who had received VV ECMO at the University Medical Center Regensburg, Germany, between 1 March 2020 and 31 December 2021. Patient-specific factors and relevant intensive-care parameters at the time of the decision to start VV ECMO were investigated regarding their value as predictors of patient survival. In addition, the intensive-care course of the first 10 days of VV ECMO was compared between survivors and patients who had died in the intensive care unit. RESULTS: The most important parameters for predicting outcome were patient age and platelet count, which differed significantly between survivors and non-survivors (age: 52.6±8.1 vs. 57.4±10.1 years, p<0.001; platelet count before VV ECMO: 321.3±132.2 vs. 262.0±121.0 /nL, p = 0.006; average on day 10: 199.2±88.0 vs. 147.1±57.9 /nL, p = 0.002). A linear regression model derived from parameters collected before the start of VV ECMO only included age and platelet count. Patients were divided into two groups by using receiver operating characteristics (ROC) analysis: group 1: 78% of patients, mortality 26%; group 2: 22% of patients, mortality 75%. A second linear regression model included average blood pH, minimum paO2, and average pump flow on day 10 of VV ECMO in addition to age and platelet count. The ROC curve resulted in two cut-off values and thus in three groups: group 1: 25% of patients, mortality 93%; group 2: 45% of patients, mortality 31%; group 3: 30% of patients, mortality 0%.

Extracorporeal life support provision in COVID-19 patients - An international EuroELSO 2022 update survey.

INTRODUCTION: An analysis on the ECLS use for patients with respiratory or cardiac support in COVID-19 based on an international response to EuroELSO survey, aims to generate a more comprehensive understanding of ECLS role during the recent viral pandemic. METHODS: EuroELSO announced the survey at the 10th annual congress in London, May 2022. The survey covered 26 multiple-choice questions. RESULTS: The survey returned 69 questionnaires from 62 centers across 22 European countries and seven centers across five non-European countries. Most of the centers providing ECLS for COVID-19 patients had more than 30 runs for respiratory support since December 2019. In the same period, at least 31 runs in adult COVID-19 patients have been performed in 48 of 69 centers (69.6%). The reported pediatric data from 18 centers is limited to less than the patients per center. CONCLUSION: Majority of the COVID-19 patients received respiratory ECLS support and adult patients dominated. The indications and contraindications are broadly aligned with available guidelines. Most of the centers considered age >65 or biological age as a relative or absolute contraindication for ECLS in COVID-19. ECLS withdrawal criteria in COVID-19 are controversial because the long-term outcomes after ECLS in COVID-19 and the impact of critical illness and the impact of long-COVID are still not known.

Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination.

Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.

Panorama

Haben Psoriasispatienten krankheitsbedingt ein erhöhtes Risiko, sich mit dem Coronavirus SARS-CoV-2 zu infizieren? Eine Frage, die viele Betroffene beschäftigt, nicht zuletzt wegen der immunsuppressiv wirkenden Therapien. Antworten lieferten kürzlich Dermatologen aus Schweden. Sie hatten an über 500 Patienten mit milder oder mittelschwerer bis schwerer Plaque-Psoriasis sowie mehr als 800 Kontrollpersonen die Häufigkeit von Atemwegsinfektionen untersucht und das Infektionsrisiko berechnet.

Determinants of antibody response to severe acute respiratory syndrome coronavirus 2 mRNA vaccines in people with HIV.

We identified determinants of SARS-CoV-2 mRNA vaccine antibody response in people with HIV (PWH). Antibody response was higher among PWH less than 60 years, with CD4+ cell count superior to 350 cells/µl and vaccinated with mRNA-1273 by Moderna compared with BNT162b2 by Pfizer-BioNTech. Preinfection with SARS-CoV-2 boosted the antibody response and smokers had an overall lower antibody response. Elderly PWH and those with low CD4+ cell count should be prioritized for booster vaccinations.

Antibody Response in Immunocompromised Patients After the Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine BNT162b2 or mRNA-1273: A Randomized Controlled Trial.

BACKGROUND: BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. METHODS: Parallel, 2-arm (allocation 1:1), open-label, noninferiority randomized clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. People living with human immunodeficiency virus (PLWH) or solid organ transplant recipients (SOTR; ie, lung and kidney) from these cohorts were randomized to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cutoff ≥0.8 units/mL) 12 weeks after first vaccination (ie, 8 weeks after second vaccination). In addition, antibody response was measured with the Antibody Coronavirus Assay 2 (ABCORA 2). RESULTS: A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI]: 88.4-95.8; 186/202) for mRNA-1273 and 94.3% (95% CI: 91.2-97.4; 198/210) for BNT162b2 (difference: -2.2%; 95% CI: -7.1 to 2.7), fulfilling noninferiority of mRNA-1273. With the ABCORA 2 test, 89.1% had an immune response to mRNA-1273 (95% CI: 84.8-93.4; 180/202) and 89.5% to BNT162b2 (95% CI: 85.4-93.7; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), whereas for SOTR, only 60.6% (95% CI: 49.2-71.9; 43/71) had titers above the cutoff level. CONCLUSIONS: In immunocompromised patients, the antibody response of mRNA-1273 was noninferior to BNT162b2. PLWH had in general an antibody response, whereas a high proportion of SOTR had no antibody response.

Evaluation of models for prognosing mortality in critical care patients with COVID-19: First- and second-wave data from a German university hospital.

BACKGROUND: In a previous study, we had investigated the intensive care course of patients with coronavirus disease 2019 (COVID-19) in the first wave in Germany by calculating models for prognosticating in-hospital death with univariable and multivariable regression analysis. This study analyzed if these models were also applicable to patients with COVID-19 in the second wave. METHODS: This retrospective cohort study included 98 critical care patients with COVID-19, who had been treated at the University Medical Center Regensburg, Germany, between October 2020 and February 2021. Data collected for each patient included vital signs, dosage of catecholamines, analgosedation, anticoagulation, and antithrombotic medication, diagnostic blood tests, treatment with extracorporeal membrane oxygenation (ECMO), intensive care scores, ventilator therapy, and pulmonary gas exchange. Using these data, expected mortality was calculated by means of the originally developed mathematical models, thereby testing the models for their applicability to patients in the second wave. RESULTS: Mortality in the second-wave cohort did not significantly differ from that in the first-wave cohort (41.8% vs. 32.2%, p = 0.151). As in our previous study, individual parameters such as pH of blood or mean arterial pressure (MAP) differed significantly between survivors and non-survivors. In contrast to our previous study, however, survivors and non-survivors in this study showed significant or even highly significant differences in pulmonary gas exchange and ventilator therapy (e.g. mean and minimum values for oxygen saturation and partial pressure of oxygen, mean values for the fraction of inspired oxygen, positive expiratory pressure, tidal volume, and oxygenation ratio). ECMO therapy was more frequently administered than in the first-wave cohort. Calculations of expected mortality by means of the originally developed univariable and multivariable models showed that the use of simple cut-off values for pH, MAP, troponin, or combinations of these parameters resulted in correctly estimated outcome in approximately 75% of patients without ECMO therapy.