The endothelium is part of your vascular system, and it plays an important role in maintaining your health. Here is a 🧵 about what the endothelium is, what it does, how SARS-CoV-2 harms it, and what that means for your health. (1/n) pic.twitter.com/OR3ttywSy3— David Lingenfelter, PhD (@dlingenfelter) August 23, 2023
A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection
European Journal of Human Genetics - A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection
Predicting human and viral protein variants affecting COVID-19 susceptibility and repurposing therapeutics
The COVID-19 disease is an ongoing global health concern. Although vaccination provides some protection, people are still susceptible to re-infection. Ostensibly, certain populations or clinical groups may be more vulnerable. Factors causing these differences are unclear and whilst socioeconomic and cultural differences are likely to be important, human genetic factors could influence susceptibility. Experimental studies indicate SARS-CoV-2 uses innate immune suppression as a strategy to speed-up entry and replication into the host cell. Therefore, it is necessary to understand the impact of variants in immunity-associated human proteins on susceptibility to COVID-19. In this work, we analysed missense coding variants in several SARS-CoV-2 proteins and its human protein interactors that could enhance binding affinity to SARS-CoV-2. We curated a dataset of 19 SARS-CoV-2: human protein 3D-complexes, from the experimentally determined structures in the Protein Data Bank and models built using AlphaFold2-multimer, and analysed impact of missense variants occurring in the protein-protein interface region. We analysed 468 missense variants from human proteins and 212 variants from SARS-CoV-2 proteins and computationally predicted their impacts on binding affinities to SARS-CoV-2 proteins, using 3D-complexes. We predicted a total of 26 affinity-enhancing variants from 14 human proteins implicated in increased binding affinity to SARS-CoV-2. These include key-immunity associated genes (TOMM70, ISG15, IFIH1, IFIT2, RPS3, PALS1, NUP98, RAE1, AXL, ARF6, TRIMM, TRIM25) as well as important spike receptors (KREMEN1, AXL and ACE2). We report both common (e.g., Y13N in IFIH1) and rare variants in these proteins and discuss their likely structural and functional impact, using information on known and predicted functional sites. Potential mechanisms associated with immune suppression implicated by these variants are discussed. Occurrence of certain predicted affinity-enhancing variants should be monitored as they could lead to increased susceptibility and reduced immune response to SARS-CoV-2 infection in individuals/populations carrying them. Our analyses aid in understanding the potential impact of genetic variation in immunity-associated proteins on COVID-19 susceptibility and help guide drug-repurposing strategies. ### Competing Interest Statement The authors have declared no competing interest.
REHVA Journal Can ventilation combat airborne infection risks in schools?
The COVID-19 pandemic caught policy makers, government agencies, school management and facility managers largely off-guard, prompting a review of existing ventilation standards in relation to the mitigating of airborne viral diseases. In light of new guidance in ASHRAE standard 241-2023 ‘Control of Infectious Aerosols’ this paper examines the relative airborne viral prophylaxis benefit of seven different ventilation scenarios, involving natural, mechanical and hybrid ventilation systems. The research aims to assess the relative merits of each approach considering current guidance in European Norm (EN 16798-1) and International Standard (ISO 17772-1) in contrast to the increased minimum equivalent clean airflow rates for classrooms in ASHRAE 241.
The results of this analysis show that increased minimum equivalent clean airflow rates have a marked effect on reducing the airborne viral transmission risk. However, even with the best performing ventilation system the risk of at least one individual becoming infected with the SARS-CoV-2 Omicron variant (after an 8 h long exposure period) was 30% (assuming that one infectious individual was present in a classroom of 20 unmasked, immunologically naïve students). By using a combined strategy involving universal FFP2 masking and ventilation the group infection risk level was dramatically reduced to 2–7% (depending on the ventilation type and flowrate) highlighting the importance of layered prophylaxis strategies at times of elevated community transmission.
Table 4. Infection risk probability
[%] results for any one individual in a group of 20Â people (with and
without universal FFP2Â masking) after 8Â hours of exposure on the
coldest day (12th of January, left) and the warmest day (30th of June, right) of the
academic year.ScenariosCold day risk (12th January) [%]Warm day risk (30th June) [%]Without masksWith masksWithout masksWith masks1. BC10027100272. MPIC-MEV 10 ℓ/s(p)4744743. MPIC-MEV 20 ℓ/s(p)3023024. AHU-HRV 10 ℓ/s(p)5755755. AHU-HRV 20 ℓ/s(p)3733836. NV-T4237277. NV-P595595 As might be expected, the results (Table 4)
show the highest risk of infection occurs in scenario 1 as there is
no active ventilation.
COVID-19: Dritter angepasster Impfstoff für Impfung in der EU zugelassen
Die Kommission hat mit dem von Novavax entwickelten Impfstoff Nuvaxovid, einen weiteren an Spikevax XBB.1.5 angepassten COVID-19-Impfstoff zugelassen. Es ist der erste angepasste Impfstoff auf Proteinbasis, der für diese Herbst- und Wintersaison zugelassen wurde.
Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts
SARS-CoV-2 needs host cells to generate molecules for viral replication and propagation. Guarnieri et al. now show that the virus is able to block expression of both nuclear-encoded and mitochondrial-encoded mitochondrial genes, resulting in impaired host mitochondrial function. They analyzed human nasopharyngeal samples and autopsy tissues from patients with COVID-19 and tissues from hamsters and mice infected with SARS-CoV-2. Host cells attempt to compensate by activating innate immune defenses and mitochondrial gene expression, but chronically impaired mitochondrial function ultimately may result in serious COVID-19 sequelae such as organ failure.
SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells
Nature Immunology - Huot et al. show that interferon-γ (IFN-γ) regulates the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in bronchoalveolar macrophages...
SARS-CoV-2 induces long-term alterations in Mac phenotypeTo explore long-term SARS-CoV-2 effects on innate immunity, we infected 25 cynomolgus macaques with wild-type (hereafter WTM, n = 15), Omicron BA.1 (n = 6) and Omicron BA.2 (n = 4) variants (hereafter OM), along with six noninfected macaques as controls (HC; Fig. 1a and Extended Data Table 1). Viral RNA loads peaked in nasal and tracheal swabs at day 3 postinfection (p.i.) in WTM and OM (7.9 × 108 and 2.78 × 107 copies per ml, respectively; Fig. 1a). Viral RNA was higher in the nasal swabs from WTM than OM (Extended Data Fig. 1a). By day 21, all macaques tested negative for SARS-CoV-2 RNA in nasal and tracheal swabs and remained negative by this readout up to 18 months p.i. (Fig. 1a). Immune responses were assessed at a median of 221 d p.i, with the analysis potentially extending to day 479 (Supplementary Table 1). Plasma immunoglobulin G (IgG) and IgA reactivities against spike and receptor-binding domain (RBD) were comparable in WTM and OM (Fig. 1b and Extended Data Fig. 1b). Inflammatory cytokines (interleukin (IL)-6, IL-18, IL-23, CXCL10) were higher in WTM and OM at 221 d.p.i. compared to HC (Extended Data Fig. 1c), suggesting lasting inflammation.
Behavioral factors and SARS-CoV-2 transmission heterogeneity within a household cohort in Costa Rica
Communications Medicine - Sun et al. investigate SARS-CoV-2 household transmission in a cohort in Costa Rica assessing behavioral factors and preventive measures. They show that behavioral factors...
Overall seroprevalence was 53% (95% confidence interval (CI) 48–58%) among household contacts. The estimated household secondary attack rate is 34% (95% CI 5–75%). Mask wearing by the index case is associated with the household transmission risk reduction by 67% (adjusted odds ratio = 0.33 with 95% CI: 0.09–0.75) and not sharing bedroom with the index case is associated with the risk reduction of household transmission by 78% (adjusted odds ratio = 0.22 with 95% CI 0.10–0.41). The estimated distribution of household secondary attack rates is highly heterogeneous across index cases, with 30% of index cases being the source for 80% of secondary cases.
Stability of Aerosolized SARS-CoV-2 on Masks and Transfer to Skin
The potential for masks to act as fomites in the transmission of SARS-CoV-2 has been suggested but not demonstrated experimentally or observationally. In this study, we aerosolized a suspension of SARS-CoV-2 in saliva and used a vacuum pump to pull the aerosol through six different types of masks. After 1 h at 28 °C and 80% RH, SARS-CoV-2 infectivity was not detectable on an N95 and surgical mask, was reduced by 0.7 log10 on a nylon/spandex mask, and was unchanged on a polyester mask and two different cotton masks when recovered by elution in a buffer. SARS-CoV-2 RNA remained stable for 1 h on all masks. We pressed artificial skin against the contaminated masks and detected the transfer of viral RNA but no infectious virus to the skin. The potential for masks contaminated with SARS-CoV-2 in aerosols to act as fomites appears to be less than indicated by studies involving SARS-CoV-2 in very large droplets.
Long-term Prognosis at 1.5 years after Infection with Wild-type strain of SARS-CoV-2 and Alpha, Delta, as well as Omicron Variants
More than three years after the first COVID-19 cases, several patients suffer from post-infectious health effects called long COVID [1, 2]. These sequelae have been defined as symptoms persisting more than 3 months after initial COVID-19 [3]. Fatigue, concentration difficulties, shortness of breath, and myalgia are among the numerous symptoms associated with long COVID [1, 4, 5]. It was early documented, that Omicron infection resulted in a milder acute course compared to previous variants [6], and understanding the risk and the characteristics of long COVID symptoms following changing variants has been of great interest for planning prevention and rehabilitation strategies.
Complement dysregulation is a predictive and therapeutically amenable feature of long COVID
Background: Long COVID encompasses a heterogeneous set of ongoing symptoms that affect many individuals after recovery from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying biological mechanisms nonetheless remain obscure, precluding accurate diagnosis and effective intervention. Complement dysregulation is a hallmark of acute COVID-19 but has not been investigated as a potential determinant of long COVID. Methods: We quantified a series of complement proteins, including markers of activation and regulation, in plasma samples from healthy convalescent individuals with a confirmed history of infection with SARS-CoV-2 and age/ethnicity/gender/infection/vaccine-matched patients with long COVID. Findings: Markers of classical (C1s-C1INH complex), alternative (Ba, iC3b), and terminal pathway (C5a, TCC) activation were significantly elevated in patients with long COVID. These markers in combination had a receiver operating characteristic predictive power of 0.794. Other complement proteins and regulators were also quantitatively different between healthy convalescent individuals and patients with long COVID. Generalized linear modeling further revealed that a clinically tractable combination of just four of these markers, namely the activation fragments iC3b, TCC, Ba, and C5a, had a predictive power of 0.785. Conclusions: These findings suggest that complement biomarkers could facilitate the diagnosis of long COVID and further suggest that currently available inhibitors of complement activation could be used to treat long COVID. Funding: This work was funded by the National Institute for Health Research (COV-LT2-0041), the PolyBio Research Foundation, and the UK Dementia Research Institute. ### Competing Interest Statement E.J.M.T. is an employee of Hycult Biotechnology. ### Funding Statement This work was funded by the National Institute for Health Research (COV-LT2-0041), the PolyBio Research Foundation, and the UK Dementia Research Institute. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Study approval was granted by the Cardiff University School of Medicine Research Ethics Committee (21/55) and by the Health Research Authority and Health and Care Research Wales (20/NW/0240). 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 data produced in the present work are shown in the manuscript. Raw data files are available upon reasonable request from the lead contact.
Neuer Höchstwert beim Krankenstand im Saarland im ersten Halbjahr 2023
In den ersten sechs Monaten dieses Jahres waren besonders viele Saarländerinnen und Saarländer krank. Die Krankenkasse AOK hat einen deutlichen Anstieg im Vergleich zum selben Zeitraum im vergangenen Jahr festgestellt. Häufige Ursache waren demnach Muskel- oder Skeletterkrankungen sowie Atemwegserkrankungen.
Adaptive variations in SARS-CoV-2 spike proteins: effects on distinct virus-cell entry stages | mBio
Continuous SARS-CoV-2 adaptations generate increasingly transmissible variants. These succeeding variants show ever-increasing evasion of suppressive antibodies and host factors, as well as increasing invasion of susceptible host cells. Here, we evaluated ...
Molecular Diagnosis of COVID-19 Sudden and Unexplained Deaths: The Insidious Face of the Pandemic
The COVID-19 epidemic has led to a significant increase in the number of deaths. This has resulted in forensic autopsies focusing on additional diagnostic possibilities. The following article is a summary of 23 autopsies of sudden and unexplained deaths. Particularly noteworthy are the described cases of children whose deaths were originally classified as SIDS (sudden infant death syndrome). All tests were performed at the Department of Forensic Medicine and Forensic Genetics, Pomeranian Medical University in Szczecin. Autopsy analyses were extended to include diagnostics of the SARS-CoV-2 virus using molecular methods and a detailed histopathological analysis of lung tissue. The material for molecular tests consisted of a nasopharyngeal swab taken postmortem and a lung tissue homogenate. In both cases, the RT-PCR method with CT cut-off point analysis was used for diagnosis. In all analyzed cases, the lungs showed massive congestion and increased fragility and cohesion. The tested material showed the presence of the SARS-CoV-2 virus, which indicated various stages of infection. It was observed that the higher the virus expression in the lungs, the lower or undetectable it was in the nasopharyngeal swab. This may explain false negative results during life in swabs. An interesting finding is that child deaths classified as SIDS also showed the presence of the virus. This may constitute a new direction of research.
Estimation of exponential growth rate and basic reproduction number of the coronavirus disease 2019 (COVID-19) in Africa - Infectious Diseases of Poverty
Background Since the first case of coronavirus disease 2019 (COVID-19) in Africa was detected on February 14, 2020, the cumulative confirmations reached 15 207 including 831 deaths by April 13, 2020. Africa has been described as one of the most vulnerable region with the COVID-19 infection during the initial phase of the outbreak, due to the fact that Africa is a great commercial partner of China and some other EU and American countries. Which result in large volume of travels by traders to the region more frequently and causing African countries face even bigger health threat during the COVID-19 pandemic. Furthermore, the fact that the control and management of COVID-19 pandemic rely heavily on a country’s health care system, and on average Africa has poor health care system which make it more vulnerable indicating a need for timely intervention to curtail the spread. In this paper, we estimate the exponential growth rate and basic reproduction number (R0) of COVID-19 in Africa to show the potential of the virus to spread, and reveal the importance of sustaining stringent health measures to control the disease in Africa. Methods We analyzed the initial phase of the epidemic of COVID-19 in Africa between 1 March and 13 April 2020, by using the simple exponential growth model. We examined the publicly available materials published by the WHO situation report to show the potential of COVID-19 to spread without sustaining strict health measures. The Poisson likelihood framework is adopted for data fitting and parameter estimation. We modelled the distribution of COVID-19 generation interval (GI) as Gamma distributions with a mean of 4.7 days and standard deviation of 2.9 days estimated from previous work, and compute the basic reproduction number. Results We estimated the exponential growth rate as 0.22 per day (95% CI: 0.20–0.24), and the basic reproduction number, R0, as 2.37 (95% CI: 2.22–2.51) based on the assumption that the exponential growth starting from 1 March 2020. With an R0 at 2.37, we quantified the instantaneous transmissibility of the outbreak by the time-varying effective reproductive number to show the potential of COVID-19 to spread across African region. Conclusions The initial growth of COVID-19 cases in Africa was rapid and showed large variations across countries. Our estimates should be useful in preparedness planning against further spread of the COVID-19 epidemic in Africa.
Instantaneous reproduction number and epidemic growth rate for predicting COVID-19 waves: the first 2 years of the pandemic in Spain
Several indicators were employed to manage the COVID-19 pandemic. In this study, our objective was to compare the instantaneous reproductive number and the epidemic growth rate in the Spanish population.Data on daily numbers of cases, admissions into ...
Global estimates of the fitness advantage of SARS-CoV-2 variant Omicron
Abstract. New variants of SARS-CoV-2 show remarkable heterogeneity in their relative fitness over both time and space. In this paper we extend the tools availab
Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants
Nature Communications - Here, Dias de Melo et al. assess the clinical, olfactory, and neuroinflammatory conditions of golden hamsters infected with SARS-CoV-2 wt and VOCs and report that viruses...
Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants
Nature Communications - Here, Dias de Melo et al. assess the clinical, olfactory, and neuroinflammatory conditions of golden hamsters infected with SARS-CoV-2 wt and VOCs and report that viruses...
