Insight
is our reward
Search

Publications in COVID-19 by NOMIS researchers

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region

NOMIS Researcher(s)

Published in

February 17, 2023

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72′250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae. © 2023 The Authors

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

DOI
10.1016/j.isci.2023.105928

Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration

NOMIS Researcher(s)

Published in

December 1, 2022

The effectiveness of therapeutic monoclonal antibodies (mAbs) against variants of the SARS-CoV-2 virus is highly variable. As target recognition of mAbs relies on tight binding affinity, we assessed the affinities of five therapeutic mAbs to the receptor binding domain (RBD) of wild type (A), Delta (B.1.617.2), and Omicron BA.1 SARS-CoV-2 (B.1.1.529.1) spike using microfluidic diffusional sizing (MDS). Four therapeutic mAbs showed strongly reduced affinity to Omicron BA.1 RBD, whereas one (sotrovimab) was less impacted. These affinity reductions correlate with reduced antiviral activities suggesting that affinity could serve as a rapid indicator for activity before time-consuming virus neutralization assays are performed. We also compared the same mAbs to serological fingerprints (affinity and concentration) obtained by MDS of antibodies in sera of 65 convalescent individuals. The affinities of the therapeutic mAbs to wild type and Delta RBD were similar to the serum antibody response, indicating high antiviral activities. For Omicron BA.1 RBD, only sotrovimab retained affinities within the range of the serum antibody response, in agreement with high antiviral activity. These results suggest that serological fingerprints provide a route to evaluating affinity and antiviral activity of mAb drugs and could guide the development of new therapeutics.

Research field(s)
Health Sciences, Biomedical Research, Biochemistry & Molecular Biology

DOI
10.1038/s41598-022-22214-z

Social alignment matters: Following pandemic guidelines is associated with better wellbeing

NOMIS Researcher(s)

Published in

December 1, 2022

Background: In response to the Covid-19 pandemic, most countries implemented physical distancing measures. Many mental health experts warned that through increasing social isolation and anxiety, these measures could negatively affect psychosocial wellbeing. However, socially aligning with others by adhering to these measures may also be beneficial for wellbeing. Methods: We examined these two contrasting hypotheses using cross-national survey data (N = 6675) collected fortnightly from participants in 115 countries over 3 months at the beginning of the pandemic. Participants reported their wellbeing, perceptions of how vulnerable they were to Covid-19 (i.e., high risk of infection) and how much they, and others in their social circle and country, were adhering to the distancing measures. Results: Linear mixed-effects models showed that being a woman, having lower educational attainment, living alone and perceived high vulnerability to Covid-19 were risk factors for poorer wellbeing. Being young (18–25) was associated with lower wellbeing, but longitudinal analyses showed that young people’s wellbeing improved over 3 months. In contrast to widespread views that physical distancing measures negatively affect wellbeing, results showed that following the guidelines was positively associated with wellbeing even for people in high-risk groups. Conclusions: These findings provide an important counterpart to the idea that pandemic containment measures such as physical distancing negatively impacted wellbeing unequivocally. Despite the overall burden of the pandemic on psychosocial wellbeing, social alignment with others can still contribute to positive wellbeing. The pandemic has manifested our propensity to adapt to challenges, particularly highlighting how social alignment can forge resilience.

Research field(s)
Health Sciences, Public Health & Health Services, Public Health

DOI
10.1186/s12889-022-13130-y

A public resource of baseline data from the Alzheimer’s Prevention Initiative Autosomal-Dominant Alzheimer’s Disease Trial

NOMIS Researcher(s)

Published in

November 14, 2022

The Alzheimer’s Prevention Initiative Autosomal-Dominant Alzheimer’s Disease (API ADAD) Trial evaluated the anti-oligomeric amyloid beta (Aβ) antibody therapy crenezumab in cognitively unimpaired members of the Colombian presenilin 1 (PSEN1) E280A kindred. We report availability, methods employed to protect confidentiality and anonymity of participants, and process for requesting and accessing baseline data. Methods: We developed mechanisms to share baseline data from the API ADAD Trial in consultation with experts and other groups sharing data from Alzheimer’s disease (AD) prevention trials, balancing the need to protect anonymity and trial integrity with making data broadly available to accelerate progress in the field. We pressure-tested deliberate and inadvertent potential threats under specific assumptions, employed a system to suppress or mask both direct and indirect identifying variables, limited and firewalled data managers, and put forth specific principles requisite to receive data. Results: Baseline demographic, PSEN1 E280A and apolipoprotein E genotypes, florbetapir and fluorodeoxyglucose positron emission tomography, magnetic resonance imaging, clinical, and cognitive data can now be requested by interested researchers. Discussion: Baseline data are publicly available; treatment data and biological samples, including baseline and treatment-related blood-based biomarker data will become available in accordance with our original trial agreement and subsequently developed Collaboration for Alzheimer’s Prevention principles. Sharing of these data will allow exploration of important questions including the differential effects of initiating an investigational AD prevention therapy both before as well as after measurable Aβ plaque deposition. © 2022 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.

Research field(s)
Health Sciences

DOI
10.1002/alz.12843

Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome—Temporally Associated With SARS-CoV-2 (PIMS-TS): Protocol of the Swissped RECOVERY Trial

NOMIS Researcher(s)

Published in

May 20, 2022

Introduction: In 2020, a new disease entitled Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C), emerged, with thousands of children affected globally. There is no available evidence based on randomized controlled trials (RCT) to date on the two most commonly used immunomodulatory treatments, intravenous immunoglobulins (IVIG) and corticosteroids. Therefore, the Swissped RECOVERY trial was conducted to assess whether intravenous (IV) methylprednisolone shortens hospital length of stay compared with IVIG. Methods and Analysis: Swissped RECOVERY is an ongoing investigator-initiated, open-label, multicenter two-arm RCT in children and adolescents <18 years hospitalized with a diagnosis of PIMS-TS. The trial is recruiting at 10 sites across Switzerland. Patients diagnosed with PIMS-TS are randomized 1:1 to methylprednisolone IV (10 mg/kg/day for 3 days) or IVIG (2 g/kg as a single dose). The primary outcome is hospital length of stay censored at day 28, death, or discharge (whichever is first). The target total sample size is ~80 patients 1:1 randomized to each study arm. Ancillary and exploratory studies on inflammation, vaccination acceptance and coverage, long-term outcomes, and healthcare costs are pre-planned. Significance: Currently, robust trial evidence for the treatment of PIMS-TS is lacking, with a controversy surrounding the use of corticosteroids vs. IVIG. This trial will provide evidence for the effectiveness and safety of these two treatments. Ethics and Dissemination: The study protocol, which was designed based on the U.K. RECOVERY trial, the patient information and consent forms, and other study-specific study documents were approved by the local ethics committees (Project ID: 2021-00362). Registration Details: The study is registered on the Swiss National Clinical Trials Portal (SNCTP000004720) and Clinicaltrials.gov (NCT 04826588).

Research field(s)
Health Sciences, Clinical Medicine, Pediatrics

DOI
10.3389/fped.2022.905046

Microfluidic Antibody Affinity Profiling Reveals the Role of Memory Reactivation and Cross-Reactivity in the Defense Against SARS-CoV-2

NOMIS Researcher(s)

Published in

April 8, 2022

Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potentially beneficial and detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be reactivated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Determining the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be disentangled by surface-based assays like enzyme-linked immunosorbent assays (ELISAs), which are routinely used to assess cross-reactivity. Here, we have used microfluidic antibody affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high-affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory reactivation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2.

Research field(s)
Natural Sciences, Chemistry, Medicinal & Biomolecular Chemistry

DOI
10.1021/acsinfecdis.1c00486

Lack of association between pandemic chilblains and SARS-CoV-2 infection

NOMIS Researcher(s)

Published in

March 1, 2022

An increased incidence of chilblains has been observed during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and attributed to viral infection. Direct evidence of this relationship has been limited, however, as most cases do not have molecular evidence of prior SARS-CoV-2 infection with PCR or antibodies. We enrolled a cohort of 23 patients who were diagnosed and managed as having SARS-CoV-2–associated skin eruptions (including 21 pandemic chilblains [PC]) during the first wave of the pandemic in Connecticut. Antibody responses were determined through endpoint titration enzyme-linked immunosorbent assay and serum epitope repertoire analysis. T cell responses to SARSCoV-2 were assessed by T cell receptor sequencing and in vitro SARS-CoV-2 antigen-specific peptide stimulation assays. Immunohistochemical and PCR studies of PC biopsies and tissue microarrays for evidence of SARS-CoV-2 were performed. Among patients diagnosed and managed as “covid toes” during the pandemic, we find a percentage of prior SARS-CoV-2 infection (9.5%) that approximates background seroprevalence (8.5%) at the time. Immunohistochemistry studies suggest that SARS-CoV-2 staining in PC biopsies may not be from SARS-CoV-2. Our results do not support SARS-CoV-2 as the causative agent of pandemic chilblains; however, our study does not exclude the possibility of SARS-CoV-2 seronegative abortive infections.

Research field(s)
Health Sciences, Clinical Medicine, Dermatology & Venereal Diseases

DOI
10.1073/pnas.2122090119

Microfluidic characterisation reveals broad range of SARS-CoV-2 antibody affinity in human plasma

NOMIS Researcher(s)

Published in

February 1, 2022

The clinical outcome of SARS-CoV-2 infections, which can range from asymptomatic to lethal, is crucially shaped by the concentration of antiviral antibodies and by their affinity to their targets. However, the affinity of polyclonal antibody responses in plasma is difficult to measure. Here we used microfluidic antibody affinity profiling (MAAP) to determine the aggregate affinities and concentrations of anti-SARS-CoV-2 antibodies in plasma samples of 42 seropositive individuals, 19 of which were healthy donors, 20 displayed mild symptoms, and 3 were critically ill. We found that dissociation constants, Kd, of anti-receptor-binding domain antibodies spanned 2.5 orders of magnitude from sub-nanomolar to 43 nM. Using MAAP we found that antibodies of seropositive individuals induced the dissociation of pre-formed spike-ACE2 receptor complexes, which indicates that MAAP can be adapted as a complementary receptor competition assay. By comparison with cytopathic effect-based neutralisation assays, we show that MAAP can reliably predict the cellular neutralisation ability of sera, which may be an important consideration when selecting the most effective samples for therapeutic plasmapheresis and tracking the success of vaccinations.

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

DOI
10.26508/lsa.202101270

Characterizing super-spreaders using population-level weighted social networks in rural communities

NOMIS Researcher(s)

Published in

January 1, 2022

Sociocentric network maps of entire populations, when combined with data on the nature of constituent dyadic relationships, offer the dual promise of advancing understanding of the relevance of networks for disease transmission and of improving epidemic forecasts. Here, using detailed sociocentric data collected over 4 years in a population of 24 702 people in 176 villages in Honduras, along with diarrhoeal and respiratory disease prevalence, we create a social-network-powered transmission model and identify super-spreading nodes as well as the nodes most vulnerable to infection, using agent-based Monte Carlo network simulations. We predict the extent of outbreaks for communicable diseases based on detailed social interaction patterns. Evidence from three waves of population-level surveys of diarrhoeal and respiratory illness indicates a meaningful positive correlation with the computed super-spreading capability and relative vulnerability of individual nodes. Previous research has identified super-spreaders through retrospective contact tracing or simulated networks. By contrast, our simulations predict that a node’s super-spreading capability and its vulnerability in real communities are significantly affected by their connections, the nature of the interaction across these connections, individual characteristics (e.g. age and sex) that affect a person’s ability to disperse a pathogen, and also the intrinsic characteristics of the pathogen (e.g. infectious period and latency). This article is part of the theme issue ‘Data science approach to infectious disease surveillance’.

Research field(s)
Applied Sciences, Enabling & Strategic Technologies, Bioinformatics

DOI
10.1098/rsta.2021.0123

Social influence matters: We follow pandemic guidelines most when our close circle does

NOMIS Researcher(s)

Published in

August 1, 2021

Why do we adopt new rules, such as social distancing? Although human sciences research stresses the key role of social influence in behaviour change, most COVID-19 campaigns emphasize the disease’s medical threat. In a global data set (n = 6,675), we investigated how social influences predict people’s adherence to distancing rules during the pandemic. Bayesian regression analyses controlling for stringency of local measures showed that people distanced most when they thought their close social circle did. Such social influence mattered more than people thinking distancing was the right thing to do. People’s adherence also aligned with their fellow citizens, but only if they felt deeply bonded with their country. Self-vulnerability to the disease predicted distancing more for people with larger social circles. Collective efficacy and collectivism also significantly predicted distancing. To achieve behavioural change during crises, policymakers must emphasize shared values and harness the social influence of close friends and family.

Research field(s)
Health Sciences, Psychology & Cognitive Sciences, Experimental Psychology

DOI
10.1111/bjop.12491

Dysregulation of brain and choroid plexus cell types in severe COVID-19

NOMIS Researcher(s)

Published in

July 22, 2021

Although SARS-CoV-2 primarily targets the respiratory system, patients with and survivors of COVID-19 can suffer neurological symptoms1–3. However, an unbiased understanding of the cellular and molecular processes that are affected in the brains of patients with COVID-19 is missing. Here we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control individuals (including 1 patient with terminal influenza) and 8 patients with COVID-19. Although our systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations indicating that barrier cells of the choroid plexus sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. We discover microglia and astrocyte subpopulations associated with COVID-19 that share features with pathological cell states that have previously been reported in human neurodegenerative disease4–6. Synaptic signalling of upper-layer excitatory neurons—which are evolutionarily expanded in humans7 and linked to cognitive function8—is preferentially affected in COVID-19. Across cell types, perturbations associated with COVID-19 overlap with those found in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia and depression. Our findings and public dataset provide a molecular framework to understand current observations of COVID-19-related neurological disease, and any such disease that may emerge at a later date.

Research field(s)
Health Sciences, Clinical Medicine, Neurology & Neurosurgery

DOI
10.1038/s41586-021-03710-0

Best Practice Recommendations for the Diagnosis and Management of Children With Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS; Multisystem Inflammatory Syndrome in Children, MIS-C) in Switzerland

NOMIS Researcher(s)

Published in

May 26, 2021

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce. Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing. Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach >80% agreement for acceptance. Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation. Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular updates of the recommendations will be warranted, and participation of patients in trials should be encouraged.

Research field(s)
Health Sciences, Clinical Medicine, Pediatrics

DOI
10.3389/fped.2021.667507

Digital contact does not promote wellbeing, but face-to-face contact does: A cross-national survey during the COVID-19 pandemic

NOMIS Researcher(s)

Published in

January 1, 2021

With restricted face-to-face interactions, COVID-19 lockdowns and distancing measures tested the capability of computer-mediated communication to foster social contact and wellbeing. In a multinational sample (n = 6436), we investigated how different modes of contact related to wellbeing during the pandemic. Computer-mediated communication was more common than face-to-face, and its use was influenced by COVID-19 death rates, more so than state stringency measures. Despite its legal and health threats, face-to-face contact was still positively associated with wellbeing, and messaging apps had a negative association. Perceived household vulnerability to COVID-19 reduced the positive effect of face-to-face communication on wellbeing, but surprisingly, people’s own vulnerability did not. Computer-mediated communication was particularly negatively associated with the wellbeing of young and empathetic people. Findings show people endeavored to remain socially connected, yet however, maintain a physical distance, despite the tangible costs to their wellbeing.

Research field(s)
Arts & Humanities, Communication & Textual Studies, Communication & Media Studies

DOI
10.1177/14614448211062164

A metabolic handbook for the COVID-19 pandemic

NOMIS Researcher(s)

Published in

July 1, 2020

For infectious-disease outbreaks, clinical solutions typically focus on efficient pathogen destruction. However, the COVID-19 pandemic provides a reminder that infectious diseases are complex, multisystem conditions, and a holistic understanding will be necessary to maximize survival. For COVID-19 and all other infectious diseases, metabolic processes are intimately connected to the mechanisms of disease pathogenesis and the resulting pathology and pathophysiology, as well as the host defence response to the infection. Here, I examine the relationship between metabolism and COVID-19. I discuss why preexisting metabolic abnormalities, such as type 2 diabetes and hypertension, may be important risk factors for severe and critical cases of infection, highlighting parallels between the pathophysiology of these metabolic abnormalities and the disease course of COVID-19. I also discuss how metabolism at the cellular, tissue and organ levels might be harnessed to promote defence against the infection, with a focus on disease-tolerance mechanisms, and speculate on the long-term metabolic consequences for survivors of COVID-19.

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

DOI
10.1038/s42255-020-0237-2

  • NOMIS Foundation 2025
  • 2025 NOMIS Foundation