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Estimating Re and overdispersion in secondary cases from the size of identical sequence clusters of SARS-CoV-2
Estimating Re and overdispersion in secondary cases from the size of identical sequence clusters of SARS-CoV-2
The wealth of genomic data that was generated during the COVID-19 pandemic provides an exceptional opportunity to obtain information on the transmission of SARS-CoV-2. Specifically, there is great interest to better understand how the effective reproduction number R e and the overdispersion of secondary cases, which can be quantified by the negative binomial dispersion parameter k , changed over time and across regions and viral variants. The aim of our study was to develop a Bayesian framework to infer R e and k from viral sequence data. First, we developed a mathematical model for the distribution of the size of identical sequence clusters, in which we integrated viral transmission, the mutation rate of the virus, and incomplete case-detection. Second, we implemented this model within a Bayesian inference framework, allowing the estimation of R e and k from genomic data only. We validated this model in a simulation study. Third, we identified clusters of identical sequences in all SARS-CoV-2 sequences in 2021 from Switzerland, Denmark, and Germany that were available on GISAID. We obtained monthly estimates of the posterior distribution of R e and k , with the resulting R e estimates slightly lower than resulting obtained by other methods, and k comparable with previous results. We found comparatively higher estimates of k in Denmark which suggests less opportunities for superspreading and more controlled transmission compared to the other countries in 2021. Our model included an estimation of the case detection and sampling probability, but the estimates obtained had large uncertainty, reflecting the difficulty of estimating these parameters simultaneously. Our study presents a novel method to infer information on the transmission of infectious diseases and its heterogeneity using genomic data. With increasing availability of sequences of pathogens in the future, we expect that our method has the potential to provide new insights into the transmission and the overdispersion in secondary cases of other pathogens. Author summary Pathogen transmission is a stochastic process that can be characterized by two parameters: the effective reproduction number R e relates to the average number of secondary cases per infectious case in the current conditions of transmission and immunity, and the overdispersion parameter k captures the variability in the number of secondary cases. While R e can be estimated well from case data, k is more difficult to quantify since detailed information about who infected whom is required. Here, we took advantage of the enormous number of sequences available of SARS-CoV-2 to identify clusters of identical sequences, providing indirect information about the size of transmission chains at different times in the pandemic, and thus about epidemic parameters. We then extended a previously defined method to estimate R e , k , and the probability of detection from this sequence data. We validated our approach on simulated and real data from three countries, with our resulting estimates compatible with previous estimates. In a future with increased pathogen sequence availability, we believe this method will pave the way for the estimation of epidemic parameters in the absence of detailed contact tracing data. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement EH, RH, and CA were supported or received funding by the Swiss National Science Foundation (No 196046). MW, JR, and CA were supported or received funding by the Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland. JR was supported by the Swiss National Science Foundation (No 189498). CA received funding from the European Union's Horizon 2020 research and innovation program - project EpiPose (No 101003688). This project was supported by the ESCAPE project (101095619), funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or European Health and Digital Executive Agency (HADEA). Neither the European Union nor the granting authority can be held responsible for them. This work was funded by UK Research and Innovation (UKRI) under the UK government's Horizon Europe funding guarantee (grant number 10051037). This work has received funding from the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract number 22.00482. EH was supported by a Swiss National Science Foundation Starting Grant (TMSGI3_211225). ### 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 Sequence data are available via GISAID after registration, and are available in EPI\_SET\_240326pm (doi.org/10.55876/gis8.240326pm) for Switzerland, EPI\_SET\_240326mz (doi.org/10.55876/gis8.240326mz) for Denmark, and EPI\_SET\_240326uh (doi.org/10.55876/gis8.240326uh) for Germany; see also the supplementary tables 1-3. Code to generate identical sequence clusters from the starting alignments is available via github.com/emmahodcroft/sc2\_rk\_public. Functions for estimation of parameters and simulation of identical sequence clusters are available via the R package estRodis github.com/mwohlfender/estRodis. Code used for the analysis of data and results as well as the creation of plots and tables is available via github.com/mwohlfender/R\_overdispersion\_cluster_size. [https://github.com/emmahodcroft/sc2\_rk\_public][1] [https://github.com/mwohlfender/R\_overdispersion\_cluster_size][2] [1]: https://github.com/emmahodcroft/sc2_rk_public [2]: https://github.com/mwohlfender/R_overdispersion_cluster_size
·medrxiv.org·
Estimating Re and overdispersion in secondary cases from the size of identical sequence clusters of SARS-CoV-2
The post-pandemic hospital and mortality burden of COVID-19 compared with influenza: A national cohort study in Denmark, May 2022 to June 2024
The post-pandemic hospital and mortality burden of COVID-19 compared with influenza: A national cohort study in Denmark, May 2022 to June 2024
Background In the post-pandemic period, COVID-19 continues to cause significant numbers of hospitalisations and deaths. We describe this burden and compare it to the burden of influenza in the first two post-pandemic years in Denmark. Methods A cohort study including residents in Denmark from May 16, 2022, to June 7, 2024. Data were obtained from national registries, including information on Polymerase chain reaction (PCR) test-positive COVID-19 and influenza admissions, mortality within 30 days of admission, sex, age, COVID-19 and influenza vaccination, comorbidity, and living in long-term care facility for elderly. Negative binomial regression was used to estimate adjusted incidence rate ratios (aIRRs) to compare rates of admissions between COVID-19 and influenza. To assess severity of COVID-19 among hospitalized patients, we used Cox proportional hazard models to estimate adjusted hazard ratios (aHR) of 30-day mortality between COVID-19 and influenza. Results Among 5,899,170 individuals, admissions with COVID-19 (n=24,687) were more frequent than admissions with influenza (n=8,682; aIRR 2.01, 95%CI 1.37-2.95), in particular during the first year (p=0.01), in the summer (p
·medrxiv.org·
The post-pandemic hospital and mortality burden of COVID-19 compared with influenza: A national cohort study in Denmark, May 2022 to June 2024
Chronic lung inflammation and CK14+ basal cell proliferation induce persistent alveolar-bronchiolization in SARS-CoV-2-infected hamsters
Chronic lung inflammation and CK14+ basal cell proliferation induce persistent alveolar-bronchiolization in SARS-CoV-2-infected hamsters
Incomplete resolution of SARS-CoV-2 infection in lung with viral residue, chronic inflammatory and fibrotic damage and alveolar-bronchiolization impaired respiratory function. Aberrant activation of CK14+ basal cells during tissue regeneration led to persistent alveolar-bronchiolization due to sustained Notch signaling. This study advances our understanding of respiratory PASC, sheds light on disease management and highlights the necessity for monitoring disease progression in people with respiratory PASC.
·thelancet.com·
Chronic lung inflammation and CK14+ basal cell proliferation induce persistent alveolar-bronchiolization in SARS-CoV-2-infected hamsters
Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey
Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey
Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining -Arginine (to improve endothelial function) and Vitamin ...
·ncbi.nlm.nih.gov·
Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey
Predicting COVID-19 booster immunogenicity against future SARS-CoV-2 variants and the benefits of vaccine updates
Predicting COVID-19 booster immunogenicity against future SARS-CoV-2 variants and the benefits of vaccine updates
Nature Communications - SARS-CoV-2 vaccines have been updated to include antigens from new variants. Here, the authors analyse data from published studies to investigate whether updating vaccines...
·nature.com·
Predicting COVID-19 booster immunogenicity against future SARS-CoV-2 variants and the benefits of vaccine updates
The influence of COVID-19 on short-term mortality in acute... : Medicine
The influence of COVID-19 on short-term mortality in acute... : Medicine
ords coronavirus disease 2019 (COVID-19), COVID-19, SARS-CoV-2, and ischemic stroke. A random-effects model was estimated, and subgroup analysis and meta-regressions were performed. The quality of eligible studies was assessed using the Newcastle-Ottawa Scale. Results: A total of 26 eligible studies with 307,800 patients were included in this meta-analysis. The overall results show that in-hospital and 90-day mortality was 3.31-fold higher in AIS with SARS-CoV-2 patients compared with those without SARS-CoV-2. When matched for age and National Institutes of Health Stroke Scale score at admission, the risk ratio of in-hospital mortality from AIS among patients with SARS-CoV-2 versus without decreased to 2.83. Reperfusion therapy and endovascular thrombectomy may further reduce the risk of death in patients to some extent but do not increase the incidence of symptomatic intracerebral hemorrhage. Meta-regression showed that in-hospital mortality decreased with increasing National Institutes of Health Stroke Scale score in AIS with SARS-CoV-2 compared to those without SARS-CoV-2 and that the difference in mortality risk between the 2 was independent of age and sex. Conclusions: The results of this study suggest that AIS patients with SARS-CoV-2 have higher short-term mortality compared to AIS patients without SARS-CoV-2, and reperfusion and endovascular thrombectomy therapy may reduce the risk of short-term mortality to some extent. The differences in in-hospital mortality risk were similar across ages and sexes. Focused attention is therefore needed on AIS patients with SARS-CoV-2 to control mortality....
·journals.lww.com·
The influence of COVID-19 on short-term mortality in acute... : Medicine
Altered functional brain connectivity, efficiency, and information flow associated with brain fog after mild to moderate COVID-19 infection
Altered functional brain connectivity, efficiency, and information flow associated with brain fog after mild to moderate COVID-19 infection
Scientific Reports - Altered functional brain connectivity, efficiency, and information flow associated with brain fog after mild to moderate COVID-19 infection
·nature.com·
Altered functional brain connectivity, efficiency, and information flow associated with brain fog after mild to moderate COVID-19 infection
Besorgniserregender Anstieg von Herzinfarkten bei jungen Erwachsenen nach COVID-19
Besorgniserregender Anstieg von Herzinfarkten bei jungen Erwachsenen nach COVID-19
DMZ – FORSCHUNG ¦ Sarah Koller ¦ Laut Bericht der New Indian Express verdeutlicht eine neue Untersuchung das Zusammenspiel von ST-Hebungsinfarkten (STEMI) und bereits vorhandenen Vorerkrankungen. In einer umfassenden fünfjährigen Analyse kardialer Patienten hat das Aakash Healthcare in Neu-Delhi festgestellt, dass die Fälle von Herzinfarkten bei Erwachsenen unter 40 Jahren in den Jahren nach der COVID-19-Pandemie mehr als doppelt so häufig auftreten. Besonders auffällig ist ein Anstieg von Notfällen um 60 Prozent. Diese Ergebnisse basieren auf der Untersuchung von 762 Fällen, die in den stationären und Notfallbereichen des Krankenhauses zwischen Mai 2018 und Oktober 2023 behandelt wurden. Die Studie unterscheidet dabei drei Zeiträume: vor der Pandemie, während der Pandemie und nach der Pandemie, jeweils über 22 Monate hinweg. Dr. Harpeet Kaur, ärztliche Leiterin des Aakash Healthcare, äußerte sich besorgt über die Erkenntnisse: „Die Ergebnisse zeichnen ein beunruhigendes Bild der kardiovaskulären Risiken in einer sich wandelnden Gesundheitslandschaft. Diese Zahlen verdeutlichen die Dringlichkeit, die zugrunde liegenden Zusammenhänge genauer zu untersuchen und präventive Maßnahmen zu ergreifen.“ Besonders beunruhigend ist der Anstieg von ST-Hebungsinfarkten (STEMI), einer schwerwiegenden Form des Herzinfarkts, bei jüngeren Menschen. Während alle Altersgruppen einen Anstieg der STEMI-Fälle nach COVID-19 verzeichneten, war der Zuwachs in der Altersgruppe unter 40 Jahren besonders dramatisch: Die Zahl der Fälle verdreifachte sich im Vergleich zur Zeit vor der Pandemie. Darüber hinaus zeigt die Studie eine enge Verbindung zwischen STEMI und bereits vorhandenen Gesundheitsproblemen wie Diabetes. Der Anteil diabetischer Patienten unter den STEMI-Fällen stieg nach der Pandemie um 50 Prozent an. Auch ein Anstieg von Bluthochdruck-Fällen wurde beobachtet, dieser war jedoch statistisch nicht signifikant. Dr. Aashish Chaudhry, Geschäftsführer des Aakash Healthcare, betonte die Dringlichkeit weiterer Forschungen: „Die statistisch signifikante Verbindung zwischen COVID-19 und der Verschlechterung der metabolischen Gesundheit sowie deren Einfluss auf das kardiovaskuläre Risiko erfordert dringend weitere Untersuchungen mit größeren Patientengruppen. Der Anstieg von STEMI-Fällen, insbesondere bei jüngeren Menschen und Diabetikern, macht präventive Maßnahmen unerlässlich.“ Die Ergebnisse dieser Studie werfen ein neues Licht auf die langfristigen gesundheitlichen Auswirkungen von COVID-19, insbesondere auf das Herz-Kreislauf-System. Angesichts der steigenden Zahl von Herzinfarkten bei jungen Erwachsenen müssen Gesundheitsbehörden verstärkt auf Prävention und Aufklärung setzen, um zukünftige Risiken zu minimieren. Zudem ist es erforderlich, weiterführende Studien durchzuführen, um das volle Ausmaß der kardiovaskulären Folgen der Pandemie zu verstehen.
·dmz-news.eu·
Besorgniserregender Anstieg von Herzinfarkten bei jungen Erwachsenen nach COVID-19
Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019 - PubMed
Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019 - PubMed
Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.
·pubmed.ncbi.nlm.nih.gov·
Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019 - PubMed
Effect of low-dose aspirin on mortality and viral duration of the hospitalized adults with COVID-19 - PubMed
Effect of low-dose aspirin on mortality and viral duration of the hospitalized adults with COVID-19 - PubMed
To clarify the effect of aspirin on mortality and viral duration in adults infected with respiratory syndrome coronavirus 2 (SARS-Cov-2).After propensity score-matched (PSM) case-control analyses 24 pairs of patients were enrolled and followed up for 2 months. Both 30-day and 60-day mortality in the …
·pubmed.ncbi.nlm.nih.gov·
Effect of low-dose aspirin on mortality and viral duration of the hospitalized adults with COVID-19 - PubMed
SARS-CoV-2-specific plasma cells are not durably established in the bone marrow long-lived compartment after mRNA vaccination
SARS-CoV-2-specific plasma cells are not durably established in the bone marrow long-lived compartment after mRNA vaccination
OpenRead Reading & Notes Taking
Nature MedicineArtice https://doi.org/10.1038/s41591-024-03278-ytetanus vaccine. S2P IgA ASCs were also detected predominantly in PopAand PopB: a mean of 1.5% (1.46 ± 1.57) and 0.9% (0.90 ± 0.66), respec-tively, and were virtually absent in PopD: a mean of 0.03% (0.03 ± 0.06)(Extended Data Fig. 3b). On average, the fold changes of IgA ASC spe-cificities within PopD were 50.9 for Flu:S2P and 9.3 for Tet:S2P (Supple-mentary Table 3). For S2P specificity, the fold change of PopA:PopD was43.8 and of PopB:PopD was 27.0 (Supplementary Table 4). Thus, similarto IgG ASCs, other class-switched isotypes such as S2P IgA ASC are alsomostly excluded from PopD (albeit small sample size).Absence of SARS-CoV-2-specific IgG in LLPC culturesupernatantTo validate the antigen-specific ELISpot results, we measured secretedIgG from BM ASC subsets (Fig. 2a; see also Methods). Briefly, from eightindividuals who yielded sufficient sorted cells for all BM ASC subsets(PopA, PopB and PopD), we cultured ASCs in a specialized in vitro BMmimetic system overnight 16 and measured the cultured supernatantsfor secreted IgG specific for Flu, Tet and S2P by multiplex bead-bindingassays (MBBAs)34 (Extended Data Fig. 4). The results were similar to thePopAPopBPopDPopAPopBPopDPopAPopBPopDPopAPopBPopDPopAPopBPopDPopAPopBPopD0246810121416BM ASC in cultureBM Flu-, Tet-, S2P-IgGASC (% total)Purple: TetGreen: S2PBlue: FluFlu Tet S2PFlu Tet S2P0131323330.61 0.4429.07Non-LLPC:LLPC ratio, IgG ASC013132333Non-LLPC:LLPC ratio, sup IgGPurple: TetGreen: S2PBlue: Flu0246713192531BM ASC in cultureSup Flu-, Tet-, S2P-IgG (% total)0.66 0.4423.26PopD PopB PopASub 8Total S2PFlu TetLLPC Non-LLPCELISpotCellsMBBASupSorting forBM ASCBM donorsASC culture(overnight)BM MNC PopA, PopB andPopD (LLPC)ASC survivalmediumBM collectionand MNC isolationa bc de fBM ASCBM ASC supFig. 2 | Absence of SARS-CoV-2 BM IgG LLPC after SARS-CoV-2 mRNA vaccinesby detection of ASC and secreted IgG in the BM ASC culture supernatants.a, Summary of the techniques and the experimental designs for detection oftotal, Flu, Tet and S2P ASCs and secreted IgG by ELISpots and MBBA, respectively.MNC, mononuclear cells. b, Representative ELISpot scanned images. Thenumbers of input ASC that were incubated were ~52 K, ~12.1 K and ~10.1 K forPopA, PopB and PopD, respectively. Each symbol represents an individualvaccine subject for total IgG and antigen-specific ASC from PopA, PopB andPopD. c, ELISpots measuring BM IgG ASC specific for Flu, Tet and S2P. Data weregenerated from 8, 15 and 17 different SARS-CoV-2-vaccinated subjects for PopA,PopB and PopD, respectively. For individual ratios and statistic comparisonsbetween any two antigens for any subset or between any two subsets for anyantigen, see Supplementary Tables 1 and 2, respectively. d, Fold difference(ratios) when comparing different vaccine specificities between non-LLPCs(combined PopA and PopB) versus LLPCs (PopD). e, MBBA measuring IgGspecific for Flu, Tet and S2P (normalized to total IgG) from culture supernatant ofPopA, PopB and PopD. Supernatant preps were collected from 18–24-h culturesof BM ASCs after revival from the FACS sorters and were quantified for total IgGand vaccine-specific IgG in neat (undiluted). Data were generated from eightdifferent SARS-CoV-2-vaccinated subjects. For individual ratios and statisticcomparisons between any two antigens for any subset or between any twosubsets for any antigen, see Supplementary Tables 1 and 2, respectively. f, Thefold difference (ratios) when comparing normalized vaccine-specific IgG in thesupernatants from the culture of non-LLPCs (combined PopA and PopB) versusLLPCs (PopD). For ratio calculation, see Methods. For IgG standard versus MFIcurve, see Extended Data Fig. 4. Counts were provided by the sorters. LLPC, boxesin b, c, and e. Sub, subject; Sups, BM ASC culture supernatant preps. For details ofsubjects and samples, see Table 1.
·openread.academy·
SARS-CoV-2-specific plasma cells are not durably established in the bone marrow long-lived compartment after mRNA vaccination
Assessment of Myocardial 18F-FDG Uptake at PET/CT in Asymptomatic SARS-CoV-2–vaccinated and Nonvaccinated Patients | Radiology
Assessment of Myocardial 18F-FDG Uptake at PET/CT in Asymptomatic SARS-CoV-2–vaccinated and Nonvaccinated Patients | Radiology
Interesting. Differences disappear 180 days after 2nd vaccination. No check with infected. Not clear if there are hidden infections.
·pubs.rsna.org·
Assessment of Myocardial 18F-FDG Uptake at PET/CT in Asymptomatic SARS-CoV-2–vaccinated and Nonvaccinated Patients | Radiology
Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study
Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study
Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM.
·thelancet.com·
Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study
SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling - Nature Communications
SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling - Nature Communications
Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction, however, the molecular pathways resulting in endothelial barrier dysfunction and vascular leakage are only sparsely understood. Here, Biering et al. show that SARS-CoV-2 spike protein is sufficient to induce barrier dysfunction and vascular leak. They show a role for integrins, TGF-beta, ECM remodeling enzymes, and glycosaminoglycans in this S-mediated barrier dysfunction.
·nature.com·
SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling - Nature Communications
Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases
Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases
An increased risk of myocarditis or pericarditis was observed after COVID-19 mRNA vaccination and was highest in men aged 18–25 years after a second dose of the vaccine. However, the incidence was rare. These results do not indicate a statistically significant risk difference between mRNA-1273 and BNT162b2, but it should not be ruled out that a difference might exist. Our study results, along with the benefit–risk profile, continue to support vaccination using either of the two mRNA vaccines.
·thelancet.com·
Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases
Brain disorders: Impact of mild SARS-CoV-2 may shrink several parts of the brain
Brain disorders: Impact of mild SARS-CoV-2 may shrink several parts of the brain
Coronavirus (COVID-19) is a highly infectious respiratory infection discovered in Wuhan, China, in December 2019. As a result of the pandemic, several individuals have experienced life-threatening diseases, the loss of loved ones, lockdowns, isolation, ...
·ncbi.nlm.nih.gov·
Brain disorders: Impact of mild SARS-CoV-2 may shrink several parts of the brain