Corpus overview


MeSH Disease

Human Phenotype

Pneumonia (27)

Fever (18)

Anosmia (8)

Stomatitis (7)

Cough (7)


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    Serology in Children TRANS with Multisystem Inflammatory Syndrome MESHD (MIS-C) associated with COVID-19

    Authors: Christina A. Rostad; Ann Chahroudi; Grace Mantus; Stacey A. Lapp; Mehgan Teherani; Lisa Macoy; Bradley S. Rostad; Sarah S. Milla; Keiko M. Tarquinio; Rajit K. Basu; Carol Kao; W. Matthew Linam; Matthew G. Zimmerman; Pei-Yong Shi; Vineet D. Menachery; Matthew E. Oster; Sri Edupuganti; Evan J. Anderson; Mehul S Suthar; Jens Wrammert; Preeti Jaggi

    doi:10.1101/2020.07.10.20150755 Date: 2020-07-11

    Objectives: We aimed to measure SARS-CoV-2 serologic responses in children TRANS hospitalized with multisystem inflammatory syndrome MESHD (MIS-C) compared to COVID-19, Kawasaki Disease MESHD (KD) and other hospitalized pediatric controls. Methods: From March 17, 2020 - May 26, 2020, we prospectively identified hospitalized children TRANS at Children TRANS's Healthcare of Atlanta with MIS-C (n=10), symptomatic PCR-confirmed COVID-19 (n=10), KD (n=5), and hospitalized controls (n=4). With IRB approval, we obtained prospective and residual blood SERO samples from these children TRANS and measured SARS-CoV-2 spike (S) receptor binding domain (RBD) IgM and IgG binding antibodies SERO by quantitative ELISA SERO and SARS-CoV-2 neutralizing antibodies SERO by live-virus focus reduction neutralization assay. We statistically compared the log-transformed antibody SERO titers among groups and performed correlation analyses using linear regression. Results: All children TRANS with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies SERO, which correlated strongly with neutralizing antibodies SERO (R2=0.667, P<0.001). Children TRANS with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody SERO titers (geometric mean titer [GMT] 6800, 95%CI 3495-13231) than children TRANS with COVID-19 (GMT 626, 95%CI 251-1563, P<0.001), children TRANS with KD (GMT 124, 95%CI 91-170, P<0.001) and other hospitalized pediatric controls (GMT 85 [all below assay limit of detection], P<0.001). All children TRANS with MIS-C also had detectable RBD IgM antibodies SERO, indicating recent SARS-CoV-2 infection MESHD. RBD IgG titers correlated with erythrocyte sedimentation rate (ESR) (R2=0.512, P<0.046) and with hospital and ICU lengths of stay (R2=0.590, P=0.010). Conclusion: Quantitative SARS-CoV-2 RBD antibody SERO titers may have a role in establishing the diagnosis of MIS-C, distinguishing it from other similar clinical entities, and stratifying risk for adverse outcomes.

    Neutralizing Antibody SERO Responses in COVID-19 Convalescent Sera

    Authors: William T Lee; Roxanne C Girardin; Alan P Dupuis II; Karen E Kulas; Anne F Payne; Susan J Wong; Suzanne Arinsburg; Freddy T Nguyen; Damodara Rao Mendu; Adolfo Firpo-Betancourt; Jeffrey Jhang; Ania Wajnberg; Florian Krammer; Carlos Cordon-Cardo; Sherlita Amler; Marisa A Montecalvo; Brad Hutton; Jill Taylor; Kathleen A McDonough

    doi:10.1101/2020.07.10.20150557 Date: 2020-07-11

    Passive transfer of antibodies SERO from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections MESHD. The United States Food and Drug Administration's (FDA) guidelines for convalescent plasma SERO recommends target antibody SERO titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies SERO in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at low (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity increased with time post symptom onset TRANS (PSO), reaching a peak at 31-35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was ~93% (PRNT50) and ~54% (PRNT90). Sera with high SARS-CoV-2 antibody SERO levels ([≥]960 ELISA SERO titers) showed maximal activity, but not all high titer sera contained neutralizing antibody SERO at FDA recommended levels, particularly at high stringency. These results underscore the value of serum SERO characterization for neutralization activity.

    Antibody SERO dynamics to SARS-CoV-2 in Asymptomatic TRANS and Mild COVID-19 patients

    Authors: Qing Lei; Yang Li; Hongyan Hou; Feng Wang; Yandi Zhang; Danyun Lai; Banga Ndzouboukou Jo-Lewis; Zhaowei Xu; Bo Zhang; Hong Chen; Zhuqing Ouyang; Junbiao Xue; Xiaosong Lin; Yunxiao Zheng; Zhongjie Yao; Xuening Wang; Caizheng Yu; Jeremy Jiang; Hainan Zhang; Huan Qi; Shujuan Guo; Shenghai Huang; Ziyong Sun; Sheng-ce Tao; Xionglin Fan

    doi:10.1101/2020.07.09.20149633 Date: 2020-07-11

    Humoral immunity in asymptomatic infections MESHD asymptomatic TRANS with SARS-CoV-2 has not been well established. 63 healthy contacts, 63 asymptomatic TRANS individuals, and 51 mild patients were enrolled in this study and screened using nucleic acid testing (NAT) and commercial kits of serum SERO IgM and IgG antibodies SERO against recombinant nucleoprotein (N) and spike (S) proteins of SARS-CoV-2. Asymptomatic TRANS and mild patients were classified into at least four types based on NAT and serological tests SERO, especially 81% and 25.4% negative NAT but positive IgM/IgG responses, respectively. Antibody SERO dynamics were further demonstrated by IgM and IgG profile responses to SARS-CoV-2 proteome. IgM antibody SERO responses against S1 were elicited in asymptomatic TRANS individuals as early to the seventh day after exposure and peaked on days from 17d to 25d, which might be used as early diagnostic biomarkers. Moreover, asymptomatic TRANS individuals evoked weaker S1 specific IgM and neutralizing antibody SERO responses than mild patients. Most importantly, S1 specific IgM/IgG responses and the titers of neutralizing antibody SERO in asymptomatic TRANS individuals gradually vanished in two months. Our findings might have important implications for serological survey, public health and immunization strategy.

    Serum SERO-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection MESHD and analysis of IgG non-responders

    Authors: Emelie Marklund; Susannah Leach; Hannes Axelsson; Kristina Nordström; Heléne Norder; Mats Bemark; Davide Angeletti; Anna Lundgren; Staffan Nilsson; Lars-Magnus Andersson; Aylin Yilmaz; Magnus Lindh; Jan-Åke Liljeqvist; Magnus Gisslén

    doi:10.1101/2020.07.11.20151324 Date: 2020-07-11

    Background: To accurately interpret COVID-19 seroprevalence SERO surveys, knowledge of serum SERO-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum SERO-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset TRANS. Results: Forty-seven patients (mean age TRANS 49 years, 38% female TRANS) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies SERO in serum SERO. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P=0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus- neutralizing antibodies SERO and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody SERO titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset TRANS. Conclusions: Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies SERO, all have detectable virus- neutralizing antibodies SERO, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence SERO surveys and for estimating the true infection MESHD prevalence SERO in populations.

    A simple protein-based SARS-CoV-2 surrogate neutralization assay

    Authors: Kento T Abe; Zhijie Li; Reuben Samson; Payman Samavarchi-Tehrani; Emelissa J Valcourt; Heidi Wood; Patrick Budylowski; Alan Dupuis; Roxie C Girardin; Bhavisha Rathod; Karen Colwill; Allison McGeer; Samira Mubareka; Jennifer L. Gommerman; Yves Durocher; Mario A Ostrowski; Kathleen McDonough; Michael A. Drebot; Steven J. Drews; James M Rini; Anne-Claude Gingras

    doi:10.1101/2020.07.10.197913 Date: 2020-07-11

    With the COVID-19 pandemic surpassing 12M confirmed cases TRANS and 550K deaths MESHD worldwide, defining the key components of the immune response to SARS-CoV-2 infection MESHD is critical. Of particular importance is the identification of immune correlates of infection MESHD that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma SERO therapy. While ELISA SERO-based assays to detect and quantitate antibodies to SARS-CoV-2 SERO in patient samples have been developed, the detection of neutralizing antibodies SERO typically requires more demanding cell-based viral assays. Here, we present and validate a safe and efficient protein-based assay for the detection of serum SERO and plasma SERO antibodies SERO that block the interaction of the SARS-CoV-2 spike (S) protein receptor binding domain (RBD) with its receptor, angiotensin converting-enzyme 2 (ACE2). This test is performed on the same platform and in parallel with an enzyme-linked immunosorbent assay SERO ( ELISA SERO) for the detection of antibodies SERO against the RBD and serves as a surrogate neutralization assay.Competing Interest StatementSteven J Drews has acted as a content expert for respiratory viruses for Johnson & Johnson (Janssen). Work in the Gingras lab was partially funded by a contribution from QuestCap through the Sinai Health Foundation. The other authors declare no relevant conflicts of interest.

    Poor correlation between antibody SERO titers and neutralizing activity in sera from SARS-CoV-2 infected subjects

    Authors: Elena Criscuolo; Roberta A Diotti; Marta Strollo; Serena Rolla; Alessandro Ambrosi; Massimo Locatelli; Roberto Burioni; Nicasio Mancini; Massimo Clementi; Nicola Clementi

    doi:10.1101/2020.07.10.20150375 Date: 2020-07-11

    Plenty of serologic tests SERO for SARS-CoV-2 have been developed so far, thus documenting the importance of evaluating the relevant features of the immune response to this viral agent. The performance SERO of these assays is currently under investigation. Amongst them, LIAISON SARS-CoV-2 S1/S2 IgG by DiaSorin and Elecsys Anti-SARS-CoV-2 cobas by Roche are currently used by laboratory medicine hospital departments in Italy and many other countries. In the present study, we have firstly compared two serologic tests SERO on serum samples SERO collected at two different time points from forty-six laboratory-confirmed COVID-19 subjects. Secondly, eighty-five negative serum samples SERO collected before the SARS-CoV-2 pandemic were analyzed. Thirdly, possible correlations between antibody SERO levels and the resulting neutralizing activity against a clinical isolate of SARS-CoV-2 were evaluated. Results revealed that both tests are endowed with low sensitivity SERO on the day of hospital admission, which increased to 97.8 and 100% for samples collected after 15 days for DiaSorin and Roche tests, respectively. The specificity of the two tests ranges from 96.5 to 100%, respectively. Importantly, a poor direct correlation between antibody SERO titers and neutralizing activity levels was evidenced in the present study.

    Clinical utility of targeted SARS-CoV-2 serology testing to aid the diagnosis and management of suspected missed, late or post-COVID-19 infection MESHD syndromes MESHD: results from a pilot service

    Authors: Nicola Sweeney; Blair Merrick; Suzanne Pickering; Rui Pedro Galao; Alina Botgros; Harry D. Wilson; Adrian W. Signell; Gilberto Betancor; Mark Kia Ik Tan; John Ramble; Neophytos Kouphou; Sam Acors; Carl Graham; Jeffrey Seow; Eithne MacMahon; Stuart J. D. Neil; Michael H. Malim; Katie Doores; Sam Douthwaite; Rahul Batra; Gaia Nebbia; Jonathan D. Edgeworth

    doi:10.1101/2020.07.10.20150540 Date: 2020-07-11

    Objectives: Determine indications and clinical utility of SARS-CoV-2 serology testing in adults TRANS and children TRANS. Design: Prospective evaluation of initial three weeks of a daily Monday to Friday pilot SARS-CoV-2 serology service for patients. Setting: Early post 'first-wave' SARS-CoV-2 transmission TRANS period at single centre London teaching hospital that provides care to the local community, as well as regional and national referral pathways for specialist services. Participants: 110 (72 adults TRANS, 38 children TRANS, age TRANS range 0-83 years, 52.7% female TRANS (n=58)). Interventions: Patient serum SERO from vetted referrals tested on CE marked and internally validated lateral flow immunoassay SERO (LFIA) (SureScreen Diagnostics) detecting antibodies to SARS-CoV-2 SERO spike proteins, with result and clinical interpretation provided to the direct care team. Main outcome measures: Performance SERO characteristics, source and nature of referrals, feasibility and clinical utility of the service, particularly the benefit for clinical decision-making. Results: The LFIA was deemed suitable for clinical advice and decision making following evaluation with 310 serum samples SERO from SARS-CoV-2 PCR positive patients and 300 pre-pandemic samples, giving a sensitivity SERO and specificity of 96.1% and 99.3% respectively. For the pilot, 115 referrals were received leading to 113 tests performed on 108 participants (sample not available for two participants); paediatrics (n=35), medicine (n=69), surgery (n=2) and general practice (n=2). 43.4% participants (n=49) had detectable antibodies to SARS-CoV-2 SERO. There were three main indications for serology; new acute presentations potentially triggered by recent COVID-19 infection MESHD e.g. PIMS-TS (n=26) and pulmonary embolism MESHD pulmonary embolism HP (n=5), potential missed diagnoses in context of a recent compatible illness (n=40), and making infection MESHD control and immunosuppression treatment decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n=6). Conclusions: This study shows acceptable performance SERO characteristics, feasibility and clinical utility of a SARS-CoV-2 serology service using a rapid, inexpensive and portable assay for adults TRANS and children TRANS presenting with a range of clinical indications. Results correlated closely with a confirmatory in-house ELISA SERO. The study showed the benefit of introducing a serology service where there is a reasonable pre-test probability, and the result can be linked with clinical advice or intervention. Experience thus far is that the volume of requests from hospital referral routes are manageable within existing clinical and laboratory services; however, the demand from community referrals has not yet been assessed. Given recent evidence for a rapid decline in antibodies SERO, particularly following mild infection MESHD, there is likely a limited window of opportunity to realise the benefit of serology testing for individuals infected during the 'first-wave' before they potentially fall HP below a measurable threshold. Rapidly expanding availability of serology services for NHS patients will also help understand the long-term implications of serostatus and prior infection MESHD in different patient groups, particularly before emergence of any 'second-wave' outbreak or introduction of a vaccination programme.

    A Highly Immunogenic Measles MESHD Virus-based Th1-biased COVID-19 Vaccine

    Authors: Cindy Hoerner; Christoph Schuermann; Arne Auste; Aileen Ebenig; Samada Muraleedharan; Maike Herrmann; Barbara Schnierle; Michael D Muehlebach

    doi:10.1101/2020.07.11.198291 Date: 2020-07-11

    The COVID-19 pandemic is caused by severe acute respiratory syndrome MESHD coronavirus-2 (SARS-CoV-2) and has spread world-wide with millions of cases and hundreds of thousands of deaths MESHD to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles MESHD virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody SERO and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody SERO responses in a protective range, multifunctional CD8+ and CD4+ T cell responses with S protein-specific killing activity were detected. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines. Significance: The COVID-19 pandemic has caused hundreds of thousands of deaths MESHD, yet. Therefore, effective vaccine concepts are urgently needed. In search for such a concept, we have analysed a measles MESHD virus-based vaccine candidate targeting SARS-CoV-2. Using this well known, safe vaccine backbone, we demonstrate here induction of functional immune responses in both arms of adaptive immunity with the desired immune bias. Therefore, occurrence of immunopathologies such as antibody SERO-dependent enhancement or enhanced respiratory disease MESHD is rather unlikely. Moreover, the candidate still induces immunity against the measles MESHD, recognized as a looming second menace, when countries are entrapped to stop routine vaccination campaigns in the face of COVID-19. Thus, a bivalent measles MESHD-based COVID-19 vaccine could be the solution for two significant public health threats.Competing Interest StatementThe authors have declared no competing interest.

    Longitudinal evaluation and decline of antibody SERO responses in SARS-CoV-2 infection MESHD

    Authors: Jeffrey Seow; Carl Graham; Blair Merrick; Sam Acors; Kathryn J.A. Steel; Oliver Hemmings; Aoife O'Bryne; Neophytos Kouphou; Suzanne Pickering; Rui Galao; Gilberto Betancor; Harry D Wilson; Adrian W Signell; Helena Winstone; Claire Kerridge; Nigel Temperton; Luke Snell; Karen Bisnauthsing; Amelia Moore; Adrian Green; Lauren Martinez; Brielle Stokes; Johanna Honey; Alba Izquierdo-Barras; Gill Arbane; Amita Patel; Lorcan OConnell; Geraldine O Hara; Eithne MacMahon; Sam Douthwaite; Gaia Nebbia; Rahul Batra; Rocio Martinez-Nunez; Jonathan D. Edgeworth; Stuart J.D. Neil; Michael H. Malim; Katie Doores

    doi:10.1101/2020.07.09.20148429 Date: 2020-07-11

    Antibody SERO (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re- infection MESHD. Using sequential serum samples SERO collected up to 94 days post onset of symptoms TRANS (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody SERO (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease MESHD severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy's and St Thomas' Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection MESHD that causes low disease MESHD severity and the circulating seasonal coronaviruses that are associated with common colds MESHD. This study has important implications when considering widespread serological testing SERO, Ab protection against re- infection MESHD with SARS-CoV-2 and the durability of vaccine protection.

    Commercial Serology Assays Predict Neutralization Activity Against SARS-CoV-2

    Authors: Raymond T Suhandynata; Melissa A Hoffman; Deli Huang; Jenny T Tran; Michael J Kelner; Sharon L Reed; Ronald W McLawhon; James E Voss; David Nemazee; Robert Fitzgerald

    doi:10.1101/2020.07.10.20150946 Date: 2020-07-11

    Background. Currently it is unknown whether a positive serology results correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value SERO of SARS-CoV-2 serology tests, especially when testing populations with low disease MESHD prevalence SERO. Methods. A neutralization assay was validated in a set of PCR confirmed positive specimens and in a negative cohort. 9,530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N=164) were reanalyzed using the neutralization assay, the Roche total immunoglobin assay, and the Abbott IgG assay. The relationship between the magnitude of a positive SARS-CoV-2 serology result and the levels of neutralizing antibodies SERO detected was correlated. Neutralizing antibody SERO titers (ID50) were also longitudinally monitored in SARS-CoV-2 PCR confirmed patients. Results. The SARS-CoV-2 neutralization assay had a PPA of 96.6% with a SARS-CoV-2 PCR test and a NPA of 98.0% across 100 negative controls. ID50 neutralization titers positively correlated with all three clinical serology platforms. Longitudinal monitoring of hospitalized PCR confirmed COVID-19 patients demonstrates they made high neutralization titers against SARS-CoV-2. PPA between the Diazyme IgG assay alone and the neutralization assay was 50.6%, while combining the Diazyme IgG assay with either the Roche or Abbott platforms increased the PPA to 79.2% and 78.4%, respectively. Conclusions. For the first time, we demonstrate that three widely available clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in COVID-19 patients. When a two-platform screen and confirm approach was used for SARS-CoV-2 serology, nearly 80% of two-platform positive specimens had neutralization titers (ID50 >50).

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MeSH Disease
Human Phenotype

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