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Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC. A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity. A whole-blood heme-metabolism signature, enriched in hospitalized patients at month 1-3 post onset, coincided with pronounced iron-deficient reticulocytosis. Lymphopenia and low numbers of dendritic cells persisted in those with PASC, and single-cell analysis reported iron maldistribution, suggesting monocyte iron loading and increased iron demand in proliferating lymphocytes. Thus, defects in iron homeostasis, dysregulated erythropoiesis and immune dysfunction due to COVID-19 possibly contribute to inefficient oxygen transport, inflammatory disequilibrium and persisting symptomatology, and may be therapeutically tractable., (© 2024. The Author(s).)

Certain serum proteins, including C-reactive protein (CRP) and D-dimer, have prognostic value in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, these factors are non-specific, providing limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations that drive the pathogenesis of severe COVID-19. To identify cellular phenotypes associated with disease, we performed a comprehensive, unbiased analysis of total and plasma-membrane PBMC proteomes from 40 unvaccinated individuals with SARS-CoV-2, spanning the whole disease spectrum. Combined with RNA sequencing (RNA-seq) and flow cytometry from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing that immune-cell dysregulation progresses with increasing disease. The cell-surface proteins CEACAMs1, 6, and 8, CD177, CD63, and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3 + CD4 + CEACAM1/6/8 + CD177 + CD63 + CD89 + and CD16 + CEACAM1/6/8 + mononuclear cells. Utilization of these markers may facilitate real-time patient assessment by flow cytometry and identify immune populations that could be targeted to ameliorate immunopathology., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: While complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood., Methods: We therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome., Results: We show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID., Conclusion: In conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted., Competing Interests: Author ET is an employee of Hycult Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hurler, Szilágyi, Mescia, Bergamaschi, Mező, Sinkovits, Réti, Müller, Iványi, Gál, Gopcsa, Reményi, Szathmáry, Lakatos, Szlávik, Bobek, Prohászka, Förhécz, Csuka, Kajdácsi, Cervenak, Kiszel, Masszi, Vályi-Nagy, Würzner, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Lyons, Toonen and Prohászka.)

The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively., (© 2023. The Author(s).)

During the coronavirus disease 2019 (COVID-19) pandemic, oncologists have managed patients at higher risk of having a severe course of this infection. This raises new questions about their correct management, as well as the difficulty of distinguishing tumor/treatments complications from those related to COVID-19. We report a case of an 11-year-old boy undergoing treatment for T-cell lymphoblastic lymphoma who experienced a prolonged COVID-19 course. Oncologic therapy was continued without significant changes compared to the initially planned treatment. No relevant complications occurred. COVID-19 convalescent plasma was administered, resulting in a positive antibody titer after 24 days.

The most commonly used markers to assess complement activation are split products that are produced through activation of all three pathways and are located downstream of C3. In contrast, C4d derives from the cleavage of C4 and indicates either classical (CP) or lectin pathway (LP) activation. Although C4d is perfectly able to distinguish between CP/LP and alternative pathway (AP) activation, no well-established markers are available to differentiate between early CP and LP activation. Active enzymes of both pathways (C1s/C1r for the CP, MASP-1/MASP-2 for the LP) are regulated by C1 esterase inhibitor (C1-INH) through the formation of covalent complexes. Aim of this study was to develop validated immunoassays detecting C1s/C1-INH and MASP-1/C1-INH complex levels. Measurement of the complexes reveals information about the involvement of the respective pathways in complement-mediated diseases. Two sandwich ELISAs detecting C1s/C1-INH and MASP-1/C1-INH complex were developed and tested thoroughly, and it was investigated whether C1s/C1-INH and MASP-1/C1-INH complexes could serve as markers for either early CP or LP activation. In addition, a reference range for these complexes in healthy adults was defined, and the assays were clinically validated utilizing samples of 414 COVID-19 patients and 96 healthy controls. The immunoassays can reliably measure C1s/C1-INH and MASP-1/C1-INH complex concentrations in EDTA plasma from healthy and diseased individuals. Both complex levels are increased in serum when activated with zymosan, making them suitable markers for early classical and early lectin pathway activation. Furthermore, measurements of C1-INH complexes in 96 healthy adults showed normally distributed C1s/C1-INH complex levels with a physiological concentration of 1846 ± 1060 ng/mL (mean ± 2SD) and right-skewed distribution of MASP-1/C1-INH complex levels with a median concentration of 36.9 (13.18 - 87.89) ng/mL (2.5-97.5 percentile range), while levels of both complexes were increased in COVID-19 patients (p<0.0001). The newly developed assays measure C1-INH complex levels in an accurate way. C1s/C1-INH and MASP-1/C1-INH complexes are suitable markers to assess early classical and lectin pathway activation. An initial reference range was set and first studies showed that these markers have added value for investigating and unraveling complement activation in human disease., Competing Interests: ET, BB, RB and WB are employees of Hycult Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hurler, Toonen, Kajdácsi, van Bree, Brandwijk, de Bruin, Lyons, Bergamaschi, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Sinkovits, Cervenak, Würzner and Prohászka.)

Background: Myocardial strain assessed with speckle tracking echocardiography is a sensitive marker of cardiac dysfunction. Both left-ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were affected by severe SARS-CoV-2 infection. However, data about cardiac involvement in patients with asymptomatic/mild Coronavirus disease-19 (COVID-19) is still lacking., Aim: To evaluate myocardial function using LV-GLS and RV-LS in patients with previous asymptomatic/mild COVID-19., Methods: Forty young adults without previously known comorbidities/cardiovascular risk factors and with a confirmed diagnosis of asymptomatic or paucisymptomatic SARS-CoV-2 infection were retrospectively included. A 2D-transthoracic echocardiogram with speckle tracking analysis was performed at least 3 months after the diagnosis. Forty healthy subjects, matched for age, sex, and body surface area in a 1:1 ratio were used as the control group., Results: Left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE) and RV-LS were comparable between the two groups. LV-GLS was significantly lower in the cases compared to the control group (-22.7 ± 1.6% vs. -25.7 ± 2.3%; p < .001). Moreover, the prevalence of regional peak systolic strain below -16% in at least two segments was three times higher in patients with previous COVID-19 compared to controls (30% vs. 10%, p = .02). In multivariable logistic regression, previous COVID-19 infection was independently associated with reduced LV-GLS values (p < .001)., Conclusion: SARS-CoV-2 infection may affect left ventricular deformation in 30% of young adult patients despite an asymptomatic or only mildly symptomatic acute illness. Speckle-tracking echocardiography could help early identification of patients with subclinical cardiac involvement, with potential repercussions on risk stratification and management., (© 2022 Wiley Periodicals LLC.)

Aim: Since 20 February 2020, Lombardy has been one of the most affected areas worldwide by the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate work and psychological impact of COVID-19 on Lombardy radiation therapy (RT) residents in the first 3 months of the outbreak (first lockdown)., Methods: An online questionnaire (22 multiple choice questions) via Microsoft Forms was administered on 30 May 2020 to RT residents., Results: Nineteen Lombardy RT residents responded to the survey. Nineteen percent of residents underwent a nasal swab and 11% were quarantined. Seventeen residents (89%) reported an increase in workload. Twelve residents (63%) did not find any difference in terms of work distress; worsening was highlighted in 5 cases (26%). The majority has never considered the possibility of stopping work due to excessive stress (89%). Almost all the residents experienced self- or relative-referred apprehension (95%). Ninety-five percent reported having missed extra-work social relationships. Most of the sample noted worsening sleep quality and difficulty concentrating (69%). No residents requested psychological support, even if provided by the hospital., Conclusion: Overall, the residents adapted to the new workplace scenario, although some health risks and well-being challenges have been reported. An extension of the survey to all Italian RT residents endorsed by Italian Association of Radiotherapy and Clinical Oncology "Young AIRO" will allow an evaluation of COVID-19 impact on a national level. A second survey is planned to underline differences between the first lockdown and the current situation of the pandemic.

COVID-19 could have a direct or indirect effect on the cardiovascular system. To detect cardiac involvement, transthoracic echocardiography is highly recommended. Considering the risk of equipment contamination and personnel exposure, mainly focused echocardiographic evaluations instead of complete examination are recommended and the use of portable devices easy to disinfect with offline reporting is highly suggested. COVID-19 could affect different sections of the heart and it is useful to analyze them separately during an echocardiographic examination. Available echocardiographic data on COVID-19 patients are scarce and do not provide definite evidence and more studies are certainly needed to better evaluate this topic., (Copyright © 2021 Elsevier Inc. All rights reserved.)

While looking for a solution to treat COVID-19, the massive off-label use of several drugs in COVID-19 has generated concerns in the early phase of the pandemic because of possible arrhythmogenic effects in relation to QTc interval prolongation. Indeed, some of these drugs have been historically associated with QT prolongation and Torsade de Point, a potentially lethal ventricular arrhythmia, and their first-time use on a very large scale has raised several concerns in the scientific community. This work aims to summarize the underlying arrhythmogenic mechanisms related to the use of potentially QT-prolonging drugs used during the pandemic to treat COVID-19., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This presentation resembles the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19., Methods: Detailed B cell phenotyping was undertaken by flow-cytometry on longitudinal samples from patients with COVID-19 across a range of severities (NIHR Cambridge BioResource). The impact of hypoxia on the transcriptome was assessed by single-cell and whole blood RNA sequencing analysis. The direct effect of hypoxia on B cells was determined through immunisation studies in genetically modified and hypoxia-exposed mice., Findings: We demonstrate the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes also observed in B cell VHL-deficient mice. These findings were associated with hypoxia-related transcriptional changes in COVID-19 patient B cells, and similar B cell abnormalities were seen in mice kept in hypoxic conditions., Interpretation: Hypoxia may contribute to the pronounced and persistent B cell pathology observed in acute COVID-19 pneumonia. Assessment of the impact of early oxygen therapy on these immune defects should be considered, as their correction could contribute to improved outcomes., Funding: Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust., Competing Interests: Declaration of interests P.H.M. declares consultancy fees from Mission Therapeutics and AstraZeneca, has received speaker honoraria from AstraZeneca, Dana Farber Cancer Institute and Astellas, participates on an advisory board for Mission Therapeutics and has a fiduciary role on committees for the Academy of Medical Sciences, Medical Schools Council and Cambridge Enterprise. J.N. declares an ITEN grant (Pfizer) to explore role of deubiquitinating enzymes in hypoxia. K.G.C.S is a co-founder and/or consultant with PredictImmune, Rheos Medicines, GSK and Kymab. M.T is on the Scientific Advisory Board of MorphogenIX. C.H. is co-founder and CSO of Hornet Therapeutics, has recently received speaker honoraria from GSK and the NIH (USA), and is board member of the Novartis Foundation for Medical-Biological Research. J.R.B has received a speaker honorarium from AstraZeneca. M.C declares an academia-industry collaborative grant from Sanofi iAward Europe to study kidney immunity, has received a speaker honorarium from Novartis and is a board member of the Medical Research Council for Population and Systems Medicine. P.A.L has received a grant from EU H2020, has received royalties and/or consulting fees from PredictImmune and Ducentis, has received a speaker honorarium from GSK and is on the committee for UKIVAS. Declaration of interests listed by these authors are outside and not related to the submitted work. All other authors have no declarations., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

B cells are important in immunity to both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and vaccination, but B cell receptor (BCR) repertoire development in these contexts has not been compared. We analyze serial samples from 171 SARS-CoV-2-infected individuals and 63 vaccine recipients and find the global BCR repertoire differs between them. Following infection, immunoglobulin (Ig)G1/3 and IgA1 BCRs increase, somatic hypermutation (SHM) decreases, and, in severe disease, IgM and IgA clones are expanded. In contrast, after vaccination, the proportion of IgD/M BCRs increase, SHM is unchanged, and expansion of IgG clones is prominent. VH1-24, which targets the N-terminal domain (NTD) and contributes to neutralization, is expanded post infection except in the most severe disease. Infection generates a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein, while a more focused response after vaccination mainly targets the spike's receptor-binding domain. Thus, the nature of SARS-CoV-2 exposure differentially affects BCR repertoire development, potentially informing vaccine strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Objective: During 2020, medical clinical activities were dramatically modified by the coronavirus disease 2019 (COVID-19) emergency. We aim to evaluate the impact of COVID-19 on radiotherapy (RT) practice in a hub cancer center., Methods: Retrospective data collection of patients with suspected COVID-19 infection, identified by pathognomonic symptoms feedback at triage realized at the entrance to RT division. Inclusion criteria were diagnosis of oncologic disease, COVID-19-related symptoms, and signed written informed consent., Results: Between 1 March and 30 June 2020, 1,006 patients accessed our RT division for RT simulation or treatment. Forty-four patients matched inclusion criteria (4.4% of all patients): 29 women and 15 men. Seventeen patients had metastatic disease. Twenty-one patients reported fever, 6 presented dyspnea, 4 complained of ageusia and anosmia, and 3 developed conjunctivitis. Thirty-six patients underwent nasal swab, with 7 positive results. From our cohort, 4 cases of pneumonia were diagnosed with computed tomography scan imaging: 3 were related to COVID-19 infection, while the fourth was evaluated as an RT adverse event. From the entire series, 4 patients died: 3 during hospitalization in intensive care unit of complications of COVID-19 and 1 of other causes neither COVID-19 nor cancer-related., Conclusions: Cancer hub allows for safe RT practice continuation while minimizing the spread of contagion in this frail patient population. A challenge for the future will be to understand pandemic consequences in cancer natural history and manage its clinical impact.

This brief report describes the SARS-CoV-2 vaccination program at our pediatric oncology unit. Adopting Italian regulations, patients treated for cancer within the previous 6 months were offered vaccination with the Pfizer-BioNtech vaccine if aged ≥16 years, and with the Pfizer-BioNtech or Moderna vaccine if aged ≥18 years. From March 24 to April 28, 2021, 80/89 adolescent and young adult patients enrolled were vaccinated, while nine refused the vaccine due to fear of side effects, disbelief regarding the pandemic, or lack of trust in the scientific community. The refusal rate in our cohort was lower than in the Italian general population., (© 2021 Wiley Periodicals LLC.)

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8 + T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications., Competing Interests: Declaration of interests The authors declare they have no competing interests. E.J.M. Toonen is an employee of Hycult Biotechnology b.v., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: There is growing evidence of cardiac injury in COVID-19. Our purpose was to assess the prognostic value of serial electrocardiograms in COVID-19 patients., Methods: We evaluated 269 consecutive patients admitted to our center with confirmed SARS-CoV-2 infection. ECGs available at admission and after 1 week from hospitalization were assessed. We evaluated the correlation between ECGs findings and major adverse events (MAE) as the composite of intra-hospital all-cause mortality or need for invasive mechanical ventilation. Abnormal ECGs were defined if primary ST-T segment alterations, left ventricular hypertrophy, tachy or bradyarrhythmias and any new AV, bundle blocks or significant morphology alterations (e.g., new Q pathological waves) were present., Results: Abnormal ECG at admission (106/216) and elevated baseline troponin values were more common in patients who developed MAE (p = .04 and p = .02, respectively). Concerning ECGs recorded after 7 days (159), abnormal findings were reported in 53.5% of patients and they were more frequent in those with MAE (p = .001). Among abnormal ECGs, ischemic alterations and left ventricular hypertrophy were significantly associated with a higher MAE rate. The multivariable analysis showed that the presence of abnormal ECG at 7 days of hospitalization was an independent predictor of MAE (HR 3.2; 95% CI 1.2-8.7; p = .02). Furthermore, patients with abnormal ECG at 7 days more often required transfer to the intensive care unit (p = .01) or renal replacement therapy (p = .04)., Conclusions: Patients with COVID-19 should receive ECG at admission but also during their hospital stay. Indeed, electrocardiographic alterations during hospitalization are associated with MAE and infection severity., (© 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16 + C1QA/B/C + ) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34 + hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8 + T cells and an increased ratio of CD8 + effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

Introduction: Data regarding real-world impact on cancer clinical research during COVID-19 are scarce. We analysed the impact of the COVID-19 pandemic on the conduct of paediatric cancer phase I-II trials in Europe through the experience of the Innovative Therapies for Children with Cancer (ITCC)., Methods: A survey was sent to all ITCC-accredited early-phase clinical trial hospitals including questions about impact on staff activities, recruitment, patient care, supply of investigational products and legal aspects, between 1st March and 30th April 2020., Results: Thirty-one of 53 hospitals from 12 countries participated. Challenges reported included staff constraints (30% drop), reduction in planned monitoring activity (67% drop of site initiation visits and 64% of monitoring visits) and patient recruitment (61% drop compared with that in 2019). The percentage of phase I, phase II trials and molecular platforms closing to recruitment in at least one site was 48.5%, 61.3% and 64.3%, respectively. In addition, 26% of sites had restrictions on performing trial assessments because of local contingency plans. Almost half of the units suffered impact upon pending contracts. Most hospitals (65%) are planning on improving organisational and structural changes., Conclusion: The study reveals a profound disruption of paediatric cancer early-phase clinical research due to the COVID-19 pandemic across Europe. Reported difficulties affected both patient care and monitoring activity. Efforts should be made to reallocate resources to avoid lost opportunities for patients and to allow the continued advancement of oncology research. Identified adaptations to clinical trial procedures may be integrated to increase preparedness of clinical research to futures crises., Competing Interests: Conflict of interest statement N. André reports a consulting or advisory role for Bayer, BMS and Akina. He received funding for trial from BMS and molecules for trials from BMS and Pierre Fabre. He received travel support from BMS. K. Nysom reports a consulting or advisory role for YmAbs and Bayer and receiving honoraria from YmAbs and Bayer. L. Marshall reports a consulting or advisory role for Bayer, BMS, Eisai and Tesaro and receiving honoraria from Bayer for speaking in symposia/educational events. M. Gambart reports a consulting or advisory role for Bayer and receiving grants for travel expenses from Jazz pharmaceutical and Eusapharma. C. Rossig reports receiving honoraria for educational presentations and advice by Amgen, Pfizer, Celgene, Roche, BMS, Novartis and Genentech. F. Fagioli reports a consultant or advisory role for Amgen, Jazz Pharmaceuticals, Pfizer, Sanofi Genzyme and Takeda. I. Øra reports a consulting or advisory role for and receiving honoraria from Bayer. B. De Wilde reports a consultant or advisory role for Bayer, Roche and Novartis. C. Rizzari reports receiving personal and/or institutional grants, travel support and consultation fees from Amgen, Jazz Pharmaceuticals, SOBI and Servier. S. Palmu reports a consulting or advisory role for Boehringer Ingelheim and receiving honoraria for educational events and travel expenses from Octapharma and Sobi. L. Moreno reports being a member of a data monitoring committees for clinical trials sponsored by Novartis, Actuate Therapeutics, Shionogi, Incyte, the University of Southampton and the Royal Marsden NHS Foundation Trust; a consulting role for Novartis and Shionogi. He also reports being a member of the Executive Committee of SIOPEN (European neuroblastoma research cooperative group), organisation which receives royalties for the sales of dinutuximab beta. He reports that his institution receives funding from sponsors for DMC participation, advisory role or conducting industry-sponsored clinical trials. F. Bautista reports a consultant or advisory role for Bayer, Amgen, Sanofi and EusaPharma and receiving honoraria for speaking at symposia from Amgen and Jazz Pharmaceuticals and support for attending symposia from Takeda, EusaPharma, Shire and Jazz Pharmaceuticals. The rest of the authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rapid COVID-19 diagnosis in the hospital is essential, although this is complicated by 30%-50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant dominates the pandemic and it is unclear how serological tests designed to detect anti-spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild-type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95% CI 57.8-92.9) by rapid NAAT alone. The combined point of care antibody test and rapid NAAT is not affected by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)