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1.
Nat Commun ; 13(1): 128, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1616978

ABSTRACT

The quality and persistence of children's humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We assess serological response at 3-4 months and 11-12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Neutralization against wild type SARS-CoV-2 and the Delta VOC are analysed in a pseudotyped virus assay. Children, compared to adults, are five times more likely to be asymptomatic, and have higher specific antibody levels which persist longer (96.2% versus 82.9% still seropositive 11-12 months post infection). Of note, symptomatic and asymptomatic infections induce similar humoral responses in all age groups. SARS-CoV-2 infection occurs independent of HCoV serostatus. Neutralization responses of children and adults are similar, although neutralization is reduced for both against the Delta VOC. Overall, the long-term humoral immune response to SARS-CoV-2 infection in children is of longer duration than in adults even after asymptomatic infection.

3.
Clin Res Cardiol ; 2021 Sep 21.
Article in English | MEDLINE | ID: covidwho-1427245

ABSTRACT

AIMS: Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients. METHODS AND RESULTS: We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056). CONCLUSIONS: Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.

4.
Artif Organs ; 45(9): 1050-1060, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1361914

ABSTRACT

Prognosis of patients suffering from acute respiratory distress syndrome (ARDS) is poor. This is especially true for immunosuppressed patients. It is controverisal whether these patients should receive veno-venous extracorporeal membrane oxygenation (VV ECMO) while evidence on this topic is sparse. We report retrospective data of a single-center registry of patients with severe ARDS requiring ECMO support between October 2010 and June 2019. Patients were analyzed by their status of immunosuppression. ECMO weaning success and hospital survival were analyzed before and after propensity score matching (PSM). Moreover, ventilator free days (VFD) were compared. A total of 288 patients were analyzed (age 55 years, 67% male), 88 (31%) presented with immunosuppression. Survival rates were lower in immunosuppressed patients (27% vs. 53%, P < .001 and 27% vs. 48% after PSM, P = .006). VFD (60 days) were lower for patients with immunosuppression (11.9 vs. 22.4, P < .001), and immunosuppression was an independent predictor for mortality in multivariate analysis. Hospital survival was 20%, 14%, 35%, and 46% for patients with oncological malignancies, solid organ transplantation, autoimmune diseases, and HIV, respectively. In this analysis immunosuppression was an independent predictor for mortality. However, there were major differences in the weaning and survival rates between the etiologies of immunosuppression which should be considered in decision making.

5.
Int J Environ Res Public Health ; 18(8)2021 04 08.
Article in English | MEDLINE | ID: covidwho-1178245

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is associated with a potentially severe clinical manifestation, coronavirus disease 2019 (COVID-19), and currently poses a worldwide challenge. Health care workers (HCWs) are at the forefront of any health care system and thus especially at risk for SARS-CoV-2 infection due to their potentially frequent and close contact with patients suffering from COVID-19. Serum samples from 198 HCWs with direct patient contact of a regional medical center and several outpatient facilities were collected during the early phase of the pandemic (April 2020) and tested for SARS-CoV-2-specific antibodies. Commercially available IgA- and IgG-specific ELISAs were used as screening technique, followed by an in-house neutralization assay for confirmation. Neutralizing SARS-CoV-2-specific antibodies were detected in seven of 198 (3.5%) tested HCWs. There was no significant difference in seroprevalence between the regional medical center (3.4%) and the outpatient institution (5%). The overall seroprevalence of neutralizing SARS-CoV-2-specific antibodies in HCWs in both a large regional medical center and a small outpatient institution was low (3.5%) at the beginning of April 2020. The findings may indicate that the timely implemented preventive measures (strict hygiene protocols, personal protective equipment) were effective to protect from transmission of an airborne virus when only limited information on the pathogen was available.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Germany/epidemiology , Health Personnel , Humans , Seroepidemiologic Studies
6.
Membranes (Basel) ; 11(3)2021 Feb 27.
Article in English | MEDLINE | ID: covidwho-1121711

ABSTRACT

The role of veno-venous extracorporeal membrane oxygenation therapy (V-V ECMO) in severe COVID-19 acute respiratory distress syndrome (ARDS) is still under debate and conclusive data from large cohorts are scarce. Furthermore, criteria for the selection of patients that benefit most from this highly invasive and resource-demanding therapy are yet to be defined. In this study, we assess survival in an international multicenter cohort of COVID-19 patients treated with V-V ECMO and evaluate the performance of several clinical scores to predict 30-day survival. METHODS: This is an investigator-initiated retrospective non-interventional international multicenter registry study (NCT04405973, first registered 28 May 2020). In 127 patients treated with V-V ECMO at 15 centers in Germany, Switzerland, Italy, Belgium, and the United States, we calculated the Sequential Organ Failure Assessment (SOFA) Score, Simplified Acute Physiology Score II (SAPS II), Acute Physiology And Chronic Health Evaluation II (APACHE II) Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score, Predicting Death for Severe ARDS on V­V ECMO (PRESERVE) Score, and 30-day survival. RESULTS: In our study cohort which enrolled 127 patients, overall 30-day survival was 54%. Median SOFA, SAPS II, APACHE II, RESP, and PRESERVE were 9, 36, 17, 1, and 4, respectively. The prognostic accuracy for all these scores (area under the receiver operating characteristic-AUROC) ranged between 0.548 and 0.605. CONCLUSIONS: The use of scores for the prediction of mortality cannot be recommended for treatment decisions in severe COVID-19 ARDS undergoing V-V ECMO; nevertheless, scoring results below or above a specific cut-off value may be considered as an additional tool in the evaluation of prognosis. Survival rates in this cohort of COVID-19 patients treated with V­V ECMO were slightly lower than those reported in non-COVID-19 ARDS patients treated with V-V ECMO.

7.
Artif Organs ; 45(6): 593-601, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-922468

ABSTRACT

Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is used to sustain blood oxygenation and decarboxylation in severe acute respiratory distress syndrome (ARDS). It is under debate if V-V ECMO is as appropriate for coronavirus disease 2019 (Covid-19) ARDS as it is for influenza. In this retrospective study, we analyzed all patients with confirmed SARS-CoV-2 or influenza A/B infection, ARDS and V-V ECMO, treated at our medical intensive care unit (ICU) between October 2010 and June 2020. Baseline and procedural characteristics as well as survival 30 days after ECMO cannulation were analyzed. A total of 62 V-V ECMO patients were included (15 with Covid-19 and 47 with influenza). Both groups had similar baseline characteristics at cannulation. Thirty days after ECMO cannulation, 13.3% of all patients with Covid-19 were discharged alive from our ICU compared to 44.7% with influenza (P = .03). Patients with Covid-19 had fewer ECMO-free days (0 (0-9.7) days vs. 13.2 (0-22.1) days; P = .05). Cumulative incidences of 30-day-survival showed no significant differences (48.6% in Covid-19 patients, 63.7% in influenza patients; P = .23). ICU treatment duration was significantly longer in ARDS patients with V-V ECMO for Covid-19 compared to influenza. Thirty-day mortality was higher in Covid-19, but not significant.


Subject(s)
COVID-19/therapy , Influenza, Human/therapy , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Adult , Aged , COVID-19/mortality , Extracorporeal Membrane Oxygenation , Female , Germany/epidemiology , Humans , Influenza, Human/mortality , Intensive Care Units , Male , Middle Aged , Registries , Respiratory Distress Syndrome/mortality , Retrospective Studies , SARS-CoV-2 , Survival Rate
8.
Clin Epidemiol ; 12: 925-928, 2020.
Article in English | MEDLINE | ID: covidwho-781765

ABSTRACT

By definition, in-hospital patient data are restricted to the time between hospital admission and discharge (alive or dead). For hospitalised cases of COVID-19, a number of events during hospitalization are of interest regarding the influence of risk factors on the likelihood of experiencing these events. The same is true for predicting times from hospital admission of COVID-19 patients to intensive care or from start of ventilation (invasive or non-invasive) to extubation. This logical restriction of the data to the period of hospitalisation is associated with a substantial risk that inappropriate methods are used for analysis. Here, we briefly discuss the most common types of bias which can occur when analysing in-hospital COVID-19 data.

9.
BMC Med Res Methodol ; 20(1): 206, 2020 08 11.
Article in English | MEDLINE | ID: covidwho-705522

ABSTRACT

BACKGROUND: The clinical progress of patients hospitalized due to COVID-19 is often associated with severe pneumonia which may require intensive care, invasive ventilation, or extracorporeal membrane oxygenation (ECMO). The length of intensive care and the duration of these supportive therapies are clinically relevant outcomes. From the statistical perspective, these quantities are challenging to estimate due to episodes being time-dependent and potentially multiple, as well as being determined by the competing, terminal events of discharge alive and death. METHODS: We used multistate models to study COVID-19 patients' time-dependent progress and provide a statistical framework to estimate hazard rates and transition probabilities. These estimates can then be used to quantify average sojourn times of clinically important states such as intensive care and invasive ventilation. We have made two real data sets of COVID-19 patients (n = 24* and n = 53**) and the corresponding statistical code publically available. RESULTS: The expected lengths of intensive care unit (ICU) stay at day 28 for the two cohorts were 15.05* and 19.62** days, while expected durations of mechanical ventilation were 7.97* and 9.85** days. Predicted mortality stood at 51%* and 15%**. Patients mechanically ventilated at the start of the example studies had a longer expected duration of ventilation (12.25*, 14.57** days) compared to patients non-ventilated (4.34*, 1.41** days) after 28 days. Furthermore, initially ventilated patients had a higher risk of death (54%* and 20%** vs. 48%* and 6%**) after 4 weeks. These results are further illustrated in stacked probability plots for the two groups from time zero, as well as for the entire cohort which depicts the predicted proportions of the patients in each state over follow-up. CONCLUSIONS: The multistate approach gives important insights into the progress of COVID-19 patients in terms of ventilation duration, length of ICU stay, and mortality. In addition to avoiding frequent pitfalls in survival analysis, the methodology enables active cases to be analyzed by allowing for censoring. The stacked probability plots provide extensive information in a concise manner that can be easily conveyed to decision makers regarding healthcare capacities. Furthermore, clear comparisons can be made among different baseline characteristics.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Betacoronavirus/drug effects , Coronavirus Infections/prevention & control , Critical Care/statistics & numerical data , Length of Stay/statistics & numerical data , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Respiration, Artificial/methods , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Algorithms , Antiviral Agents/therapeutic use , Betacoronavirus/physiology , COVID-19 , Cohort Studies , Compassionate Use Trials/methods , Coronavirus Infections/mortality , Coronavirus Infections/virology , Critical Care/methods , Humans , Intensive Care Units/statistics & numerical data , Models, Theoretical , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , SARS-CoV-2 , Survival Analysis , Survival Rate , Time Factors
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