The influence of mechanical ventilation and portable air cleaners upon aerosol spread in a hospital outpatients clinic
The SARS-CoV-2 global pandemic has highlighted the risk of nosocomial infections of airborne viruses to patient populations around the world. Increased use of mechanical ventilation and portable air cleaners (PACs) have been suggested as methods to mitigate this risk, but the introduction of new air flows to indoor areas can have complex and potentially unforeseen consequences. We used particle counters to investigate the effect of using built-in mechanical ventilation and/or PACs in a typical hospital outpatients’ clinic upon the spread of aerosols produced by an aerosol generator. A variety of scenarios was investigated, examining particle movement to a neighboring room, throughout the whole clinic, and from one room to another at the far side of the clinic. Whilst both built-in ventilation and PACs may reduce particle migration in some scenarios by up to 96%, use of the same PACs may lead to unexpectedly increased aerosol migration of 29% between neighboring rooms, and use of built-in supply ventilation may increase aerosol migration across the clinic by up to 5.5 times. These increases are most likely due to the introduction of air flows from the outlets of these devices, providing aerosols with enough momentum to traverse the distance between relatively remote locations or creating recirculation regions that pull aerosols out of one room and push them into another. Accordingly, in order to effectively deploy these useful mitigations to their full potential and not simply displace the risk of nosocomial infection, careful consideration of placement and resultant air flow dynamics is required.
KP.2-based monovalent mRNA vaccines robustly boost antibody responses to SARS-CoV-2
In response to the ongoing evolution of SARS-CoV-2, vaccine manufacturers have released updated COVID-19 vaccines annually since 2022. For much of 2024, the global spread was dominated by the JN.1 lineage of viruses,1 which are antigenically quite distant from the XBB.1.5 variant that was used in the previous vaccine booster.2 In August 2024, the US Food and Drug Administration authorised two updated mRNA vaccines (Pfizer–BioNTech and Moderna) based on the spike sequence of KP.2, a subvariant in the JN.1 lineage.3 In the UK and the EU, a KP.2-based mRNA vaccine (BioNTech) was also authorised later in the year.4,5 We have now provided the first indication of the acute boosting effect of updated KP.2 monovalent mRNA vaccines (KP.2 MV) on serum SARS-CoV-2 neutralising antibodies in humans.Since the authorisation of the updated vaccine boosters, SARS-CoV-2 has evolved beyond KP.2, with the subvariant KP.3.1.1 becoming dominant globally and the subvariant XEC now gaining traction rapidly.1 KP.2 contains Arg346Thr, Phe456Leu, and Val1104Leu mutations in spike, in addition to those present in the parental JN.1 (figure A). Both KP.3.1.1 and XEC share Phe456Leu and Val1104Leu mutations found in KP.2, along with Gln493Glu, which is absent in KP.2. In addition, KP.3.1.1 harbors the Ser31del mutation, whereas XEC carries Thr22Asn and Phe59Ser mutations; neither KP.3.1.1 nor XEC possess the Arg346Thr mutation (figure A). The effectiveness of the updated KP.2 MV boosters on neutralising antibodies in human serum against recently dominant subvariants has yet to be reported.
SARS-CoV-2 infection linked to rapid plaque growth in coronary arteries
A new study found severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was associated with the rapid growth of plaque in the coronary arteries and an increased risk of cardiovascular events.
There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.
Aberrations in medically certified sick leave and primary healthcare consultations in Norway in 2023 compared to pre-COVID-19-pandemic trends - Archives of Public Health
Background Since 2022, Norway has employed a vaccine-only COVID-19 strategy. Primary healthcare in Norway uses International Classification of Primary Care version 2 (ICPC-2) codes. This study aims to systematically compare medically certified sick leave and primary healthcare consultations in 2023 with the pre-pandemic 2010–2019 trends, and subsequently estimate the magnitude of these changes. Methods For the respective outcomes of (A) working person-years lost to medically certified sick leave (WYLSL) and (B) number of primary healthcare consultations, 556 and 85 ICPC-2 code combinations were extracted from the Norwegian Labour and Welfare Administration’s sick leave registry and the Norwegian Syndromic Surveillance System. For each ICPC-2 code combination, a Bayesian linear regression was performed using data between 2010 and 2019 to estimate an expected baseline for 2023, which was then used to calculate the deviation from the pre-pandemic trend. A false discovery rate of 5% was used to account for multiple testing. Results All years from 2020 to 2023 had excess WYLSL, corresponding to 14,491 (90% PI: 8,935 to 20,016) in 2020, 12,911 (90% PI: 5,916 to 19,996) in 2021, 21,263 (90% PI: 12,627 to 29,864) in 2022, and 24,466 (90% PI: 14,023 to 34,705) in 2023. This corresponded to an economic loss of approximately 1.5 billion USD in 2023. Excess WYLSL due to A* (General and unspecified) increased from 2020 to 2023, with an estimated excess of 4,136 WYLSL in 2023 (69% higher than expected). More than half of this increase was explained by A04 (Weakness/tiredness general), whose excess WYLSL in 2023 were estimated at 2,640 (80% higher than expected). The excess in A04 (Weakness/tiredness general) corresponded to an economic loss of 161 million USD and accounted for 11% of the total excess WYLSL in 2023. The excess WYLSL in R* (Respiratory) in 2023 was 3,408, which correspond to an economic loss of 207 million USD and accounted for 14% of the total excess in 2023. Conclusions Significant excesses in working person-years lost to medically certified sick leave and primary healthcare consultations in 2023. A sizable proportion of the excesses were due to diseases/symptoms associated with acute and post-acute sequelae of COVID-19.
National- and state-level SARS-CoV-2 immunity trends from January 2020 to December 2023: a mathematical modeling analysis
Introduction Effective immune protection against SARS-CoV-2 infection and severe COVID-19 disease continues to change due to viral evolution and waning immunity. We estimated population-level immunity to SARS-CoV-2 for each of the fifty United States (U.S.) and the District of Columbia from January 2020 through December 2023. Methods We updated a model of SARS-CoV-2 infections to align with the latest evidence on SARS-CoV-2 natural history and waning of immunity, and to integrate various data sources available throughout the pandemic. We used this model to produce population estimates of effective protection against SARS-CoV-2 infection and severe COVID-19 disease. Results On December 30, 2023, 99.9% of the U.S. population had experienced immunological exposure to SARS-CoV-2 through infection and/or vaccination, with 99.4% (95% credible interval (CrI): 92.4-100%) having had at least one SARS-CoV-2 infection. Despite this high exposure, the average population-level protection against infection was 53.6% (95% CrI: 38.7-71.5%). Population-level protection against severe disease was 82.6% (95% CrI: 71.5-91.7%). Discussion A new wave of SARS-CoV-2 infections and COVID-19-associated hospitalizations began near the end of 2023, with the introduction of the JN.1 variant. This upturn suggests that the U.S. population remains at risk of SARS-CoV-2 infection and severe COVID-19 disease despite the high level of cumulative exposure in the United States. This decline in effective protection is likely due to both waning and continued viral evolution. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project has been funded (in part) by contract number 200-2016-91779 with the Centers for Disease Control and Prevention (CDC) and funding from the Centers for Disease Control and Prevention through the Council of State and Territorial Epidemiologists (Grant Number NU3OT000297). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All code and data used in this analysis are available on GitHub (). The produced datasets are available on the Harvard Dataverse ().
Reha-Effekte bei Long Covid: „Irreführung“ der Rentenversicherung
Die Rentenversicherung sagt, eine Studie belege den Nutzen einer Reha bei Long Covid. Doch die Studie, auf die sie sich beruft, gibt das gar nicht her. Groß sind hingegen die Interessenkonflikte.
Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection
Nature Medicine - Blood biomarkers in a middle-aged population suggest that SARS-CoV-2 infection is associated with greater brain β-amyloid plaque accumulation.
P0304 SARS-COV-2 in Colorectal Cancer of IBD Patients
AbstractBackground. It has been hypothesized that inflammation related to SARS-CoV-2 infection can affect cancer cell proliferation, without having a direc
Evolution of SARS-CoV-2 T cell responses as a function of multiple COVID-19 boosters
The long-term effects of repeated COVID-19 vaccinations on adaptive immunity remain incompletely understood. Here, we conducted a comprehensive three-year longitudinal study examining T cell and antibody responses in 78 vaccinated individuals without reported symptomatic infections. We observed distinct dynamics in Spike-specific humoral and cellular immune responses across multiple vaccine doses. While antibody titers incrementally increased and stabilized with each booster, T cell responses rapidly plateaued, maintaining remarkable stability across CD4+ and CD8+ subsets. Notably, approximately 30% of participants showed CD4+ T cell reactivity to non-Spike antigens, consistent with asymptomatic infections. Single-cell RNA sequencing revealed a diverse landscape of Spike-specific T cell phenotypes, with no evidence of increased exhaustion or significant functional impairment. However, qualitative changes were observed in individuals with evidence of asymptomatic infection, exhibiting unique immunological characteristics, including increased frequencies of Th17-like CD4+ T cells and GZMKhi/IFNR CD8+ T cell subsets. Remarkably, repeated vaccinations in this group were associated with a progressive increase in regulatory T cells, potentially indicating a balanced immune response that may mitigate immunopathology. By regularly stimulating T cell memory, boosters contribute to a stable and enhanced immune response, which may provide better protection against symptomatic infections. ### Competing Interest Statement A.S. is a consultant for Darwin Health, EmerVax, Gilead Sciences, Guggenheim Securities, RiverVest Venture Partners, and Arcturus. D.W. is a consultant for Moderna. S.C. has consulted for GSK, JP Morgan, Citi, Morgan Stanley, Avalia NZ, Nutcracker Therapeutics, University of California, California State Universities, United Airlines, Adagio, and Roche. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work.
Study uncovers distinct blood protein signature in children with Long COVID
Distinct protein profiles linked to inflammation and angiogenesis found in children with Long COVID, paving the way for improved diagnostics and therapies.
Kanadische Studie: 38% Long Covid-Risiko nach 3. Infektion
Während sich ein großer Teil der Bevölkerung bezüglich Covid-19 weiterhin in Scheinsicherheit wiegt, zeichnen Daten ein anderes Bild: Eine kanadische Studie aus dem Jahr 2023 unter dem Titel „…
Genome analysis of SARS-CoV-2 haplotypes: separation and parallel evolution of the major haplotypes occurred considerably earlier than their emergence in China
More than 3 years have passed since the outbreak of COVID-19 and yet, the origin of the causal virus SARS-CoV-2 remains unknown. We examined the evolu…
High throughput spatial immune mapping reveals an innate immune scar in post-COVID-19 brains
Acta Neuropathologica - The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine...
SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory, physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids
Long COVID is a major public health consequence of COVID-19 and is characterized by multiple neurological and neuropsychatric symptoms. SARS-CoV-2 ant…
Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic
SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging to comprehensively compare the many spikes that emerged during the pandemic in a single experimental platform. Here we generated a panel of recombinant viruses carrying different spike proteins from 27 variants circulating between 2020 and 2024 in the same genomic background. We then assessed several of their phenotypic traits both in vitro and in vivo. We found distinct phenotypic trajectories of spike among and between variants circulating before and after the emergence of Omicron variants. Spike of post-Omicron variants maintained enhanced tropism for the nasal epithelium and large airways but displayed, over time, several phenotypic traits typical of the pre-Omicron variants. Hence, spike with phenotypic features of both pre- and post-Omicron variants may continue to emerge in the future.