Intramuscular SARS-CoV-2 vaccines elicit varying degrees of plasma and salivary antibody responses as compared to natural infection
Vaccination induced antibody and T-cell immune responses are important for systemic protection from COVID-19. Because SARS-CoV-2 infects and is transmitted by oral-pharyngeal mucosa, we wished to test mucosal antibodies elicited by natural infection or intramuscular vaccine injection. In a non-randomized observational study, we measured antibodies against the SARS-CoV-2 RBD in plasma and saliva from convalescent or vaccinated individuals and tested their neutralizing potential using a replication competent rVSV-eGFP-SARS-CoV-2. We found IgG and IgA anti-RBD antibodies as well as neutralizing activity in convalescent plasma and saliva. Two doses of mRNA vaccination (BNT162b2 or mRNA-1273) induced high levels of IgG anti-RBD in saliva, a subset of whom also had IgA, and significant neutralizing activity. We detected anti-RBD IgG and IgA with significant neutralizing potential in the plasma of single dose Ad26.COV2.S vaccinated individuals, and we detected slight amounts of anti-RBD antibodies in matched saliva. The role of salivary antibodies in protection against SARS-CoV-2 infection is unknown and merits further investigation. This study was not designed to, nor did it study the full kinetics of the antibody response or protection from infection, nor did it address variants of SARS-CoV-2. ### Competing Interest Statement None of the authors have any financial involvement with any of the companies mentioned in this manuscript. Dr. Nadeau reports grants from National Institute of Allergy and Infectious Diseases (NIAID), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Environmental Health Sciences (NIEHS), and Food Allergy Research & Education (FARE); Director of World Allergy Organization (WAO), Advisor at Cour Pharma, co-founder of Before Brands, Alladapt, Latitude, and IgGenix; and National Scientific Committee member at Immune Tolerance Network (ITN), and National Institutes of Health (NIH) clinical research centers, outside the submitted work; patents include, Mixed allergen composition and methods for using the same, Granulocyte-based methods for detecting and monitoring immune system disorders, and Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders. M.C.T. consults for Orca Bio, Guidepoint, and is an advisor at Acari Bio. ### Clinical Trial Samples from [NCT04373148][1] and [NCT04505722][2] were used in this study. All other samples are part of an observational, non-interventional study. ### Funding Statement Research reported in this publication was supported by: The Fairbairn Family Foundation, The Stanford SPARK Program, Virginia and D.K. Ludwig Fund for Cancer Research. M.C.T., S.G. and P.H. were supported by the Bay Area Lyme Foundation, M.C.T also supported by Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation. G.R.N. and G.B. were supported by the Younger Family Foundation. R.S.S. was supported by Fairbairn Family Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### 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: Stanford University Research Compliance Office (IRB 57277) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The code generated during this study is available at: [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04373148&atom=%2Fmedrxiv%2Fearly%2F2021%2F08%2F30%2F2021.08.22.21262168.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04505722&atom=%2Fmedrxiv%2Fearly%2F2021%2F08%2F30%2F2021.08.22.21262168.atom
Systemic COVID-19 vaccination also enhances the humoral immune response after SARS CoV-2 infection. An approach to criteria for COVID-19 re-immunization is needed. Do we need a third dose?
Systemic vaccination of the BNT162b2 mRNA stimulates humoral response. The aim of our study was to compare the intensity of humoral immune response, measured by SARS CoV-2 IgG, SARS CoV-2 IgM, and neutralization S-RBD IgG antibodies level, post COVID-19 vaccination versus post SARS COV-2 infectio...
Misinformation can prevent the suppression of epidemics
The effectiveness of non-pharmaceutical interventions, such as mask-wearing and social distancing, as control measures for pandemic disease relies upon a conscientious and well-informed public who are aware of and prepared to follow advice. Unfortunately, public health messages can be undermined by competing misinformation and conspiracy theories, spread virally through communities that are already distrustful of expert opinion. In this article, we propose and analyse a simple model of the interaction between disease spread and (mis-) information dynamics in a heterogeneous population composed of both trusting individuals who seek quality information and will take precautionary measures, and distrusting individuals who are susceptible to misinformation. We show that, as the density of the distrusting population increases, the model passes through a phase transition to a state in which major outbreaks cannot be suppressed. Our work highlights the urgent need for effective measures to combat the spread of misinformation.
### Competing Interest Statement
The authors have declared no competing interest.
### Funding Statement
A.S. is supported by a scholarship from the EPSRC Centre for Doctoral Training in Statistical Applied Mathematics at Bath (SAMBa), under the project EP/S022945/1. T.R. acknowledges the support of the Royal Society RGF\EA\180242.
### 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:
Not applicable.
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Not applicable.
Seroconversion and fever are dose-pependent in a nonhuman primate model of inhalational COVID-19
Author summary SARS-CoV-2 infection and subsequent disease presentation are dependent on exposure dose in a nonhuman primate model of inhalational COVID-19.
Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study
This large national study found a higher hospital admission or emergency care attendance
risk for patients with COVID-19 infected with the delta variant compared with the
alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated
populations might lead to a greater burden on health-care services than the alpha
variant.
COVID-19 vaccine effectiveness against hospitalizations was stable, but it declined against new infections among adults in New York during May–July 2021.
mRNA Vaccination Induces Durable Immune Memory to SARS-CoV-2 with Continued Evolution to Variants of Concern
SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naïve and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination. Antibody and neutralizing titers decayed from peak levels but remained detectable in all subjects at 6 months post-vaccination. Functional memory B cell responses, including those specific for the receptor binding domain (RBD) of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants, were also efficiently generated by mRNA vaccination and continued to increase in frequency between 3 and 6 months post-vaccination. Notably, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern, and B cell receptor sequencing revealed significantly more hypermutation in these RBD variant-binding clones compared to clones that exclusively bound wild-type RBD. Moreover, the percent of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19. mRNA vaccination also generated antigen-specific CD8+ T cells and durable memory CD4+ T cells in most individuals, with early CD4+ T cell responses correlating with humoral immunity at later timepoints. These findings demonstrate robust, multi-component humoral and cellular immune memory to SARS-CoV-2 and current variants of concern for at least 6 months after mRNA vaccination. Finally, we observed that boosting of pre-existing immunity with mRNA vaccination in SARS-CoV-2 recovered individuals primarily increased antibody responses in the short-term without significantly altering antibody decay rates or long-term B and T cell memory. Together, this study provides insights into the generation and evolution of vaccine-induced immunity to SARS-CoV-2, including variants of concern, and has implications for future booster strategies.
![Figure][1]
### Competing Interest Statement
AS is a consultant for Gritstone, Flow Pharma, CellCarta, Arcturus, Oxfordimmunotech, and Avalia. La Jolla Institute for Immunology has filed for patent protection for various aspects of T cell epitope and vaccine design work. SEH has received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merk for work unrelated to this report. ELP is consulting or an advisor for Roche Diagnostics, Enpicom, The Antibody Society, IEDB, and The American Autoimmune Related Diseases Association. EJW is consulting or is an advisor for Merck, Marengo, Janssen, Related Sciences, Synthekine and Surface Oncology. EJW is a founder of Surface Oncology, Danger Bio and Arsenal Biosciences. EJW is an inventor on a patent (US Patent number 10,370,446) submitted by Emory University that covers the use of PD-1 blockade to treat infections and cancer.
[1]: pending:yes
(22) Otto Kolbl auf Twitter: "Antibody tests, even microneutr., might not necessarily indicate SARS-CoV-2. We need PCR tests, if possible with sequencing. In north of Paris, after combing through 124 ICU patient records, 14 selected for PCR tests, 1 positive SARS-CoV-2. So easy! 5/13 https://t.co/PNHxWjvJTi" / Twitter
Antibody tests, even microneutr., might not necessarily indicate SARS-CoV-2. We need PCR tests, if possible with sequencing. In north of Paris, after combing through 124 ICU patient records, 14 selected for PCR tests, 1 positive SARS-CoV-2. So easy! 5/13
https://t.co/PNHxWjvJTi
Waning of BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar
BACKGROUND: Waning of vaccine protection against SARS-CoV-2 infection or COVID-19 disease is a concern. This study investigated persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the Beta and Delta variants have dominated incidence and PCR testing is done at a mass scale. METHODS: A matched test-negative, case-control study design was used to estimate vaccine effectiveness against SARS-CoV-2 infection and against any severe, critical, or fatal COVID-19 disease, between January 1, 2021 to August 15, 2021. RESULTS: Estimated BNT162b2 effectiveness against any infection, asymptomatic or symptomatic, was negligible for the first two weeks after the first dose, increased to 36.5% (95% CI: 33.1-39.8) in the third week after the first dose, and reached its peak at 72.1% (95% CI: 70.9-73.2) in the first five weeks after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating ≥15 weeks after the second dose, reaching diminished levels of protection by the 20th week. Effectiveness against symptomatic infection was higher than against asymptomatic infection, but still waned in the same fashion. Effectiveness against any severe, critical, or fatal disease increased rapidly to 67.7% (95% CI: 59.1-74.7) by the third week after the first dose, and reached 95.4% (95% CI: 93.4-96.9) in the first five weeks after the second dose, where it persisted at about this level for six months. CONCLUSIONS: BNT162b2-induced protection against infection appears to wane rapidly after its peak right after the second dose, but it persists at a robust level against hospitalization and death for at least six months following the second dose.
### Competing Interest Statement
The authors have declared no competing interest.
### Funding Statement
The authors are grateful for institutional salary support from the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, as well as for institutional salary support provided by the Ministry of Public Health and Hamad Medical Corporation. The authors are also grateful for the Qatar Genome Programme for institutional support for the reagents needed for the viral genome sequencing. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the article. Statements made herein are solely the responsibility of the authors.
### 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:
The study was approved by the Hamad Medical Corporation and Weill Cornell Medicine-Qatar Institutional Review Boards with waiver of informed consent.
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
The dataset of this study is a property of the Qatar Ministry of Public Health that was provided to the researchers through a restricted-access agreement that prevents sharing the dataset with a third party or publicly. Future access to this dataset can be considered through a direct application for data access to Her Excellency the Minister of Public Health (https://www.moph.gov.qa/english/Pages/default.aspx). Aggregate data are available within the manuscript and its Supplementary information.
Die meisten Kinder und Jugendlichen haben eine SARS-CoV-2-Infektion gut bewältigen können. Dennoch sind einige von ihnen von den Folgen im Sinne eines Long COVID betroffen. Dieses Beschwerdebild gilt es – nicht zuletzt im Hinblick auf psychische...
Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections
Background: Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. Methods: We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naive individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P
Physical phenotype of blood cells is altered in COVID-19
Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory
syndrome coronavirus 2 is characterized by rapid spreading and high mortality worldwide.
Although the pathology is not yet fully understood, hyperinflammatory response and
coagulation disorders leading to congestions of microvessels are considered to be
key drivers of the still-increasing death toll. Until now, physical changes of blood
cells have not been considered to play a role in COVID-19 related vascular occlusion
and organ damage.
Do school closures and school reopenings affect community transmission of COVID-19? A systematic review of observational studies
Objectives To systematically reivew the observational evidence of the effect of school closures and school reopenings on SARS-CoV-2 community transmission.
Setting Schools (including early years settings, primary schools and secondary schools).
Intervention School closures and reopenings.
Outcome measure Community transmission of SARS-CoV-2 (including any measure of community infections rate, hospital admissions or mortality attributed to COVID-19).
Methods On 7 January 2021, we searched PubMed, Web of Science, Scopus, CINAHL, the WHO Global COVID-19 Research Database, ERIC, the British Education Index, the Australian Education Index and Google, searching title and abstracts for terms related to SARS-CoV-2 AND terms related to schools or non-pharmaceutical interventions (NPIs). We used the Cochrane Risk of Bias In Non-randomised Studies of Interventions tool to evaluate bias.
Results We identified 7474 articles, of which 40 were included, with data from 150 countries. Of these, 32 studies assessed school closures and 11 examined reopenings. There was substantial heterogeneity between school closure studies, with half of the studies at lower risk of bias reporting reduced community transmission by up to 60% and half reporting null findings. The majority (n=3 out of 4) of school reopening studies at lower risk of bias reported no associated increases in transmission.
Conclusions School closure studies were at risk of confounding and collinearity from other non-pharmacological interventions implemented around the same time as school closures, and the effectiveness of closures remains uncertain. School reopenings, in areas of low transmission and with appropriate mitigation measures, were generally not accompanied by increasing community transmission. With such varied evidence on effectiveness, and the harmful effects, policymakers should take a measured approach before implementing school closures; and should look to reopen schools in times of low transmission, with appropriate mitigation measures.
All data relevant to the study are included in the article or uploaded as supplemental information. All included data in this systematic review are already in the public domain.
Changing Dynamics of COVID-19 in the U.S. with the Emergence of the Delta Variant: Projections of the COVID-19 Simulator
With the recent emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2 in the U.S., many states are seeing rising cases and hospitalizations after a period of steady decline. As We used the COVID-19 Simulator , an interactive online tool that utilizes a validated mathematical model, to simulate the trajectory of COVID-19 at the state level in the U.S. COVID-19 Simulator’s forecasts are updated weekly and included in the Centers for Disease Control and Prevention (CDC) ensemble model. We employed our model to analyze scenarios where the Delta variant becomes dominant in every state.
The combination of high transmissibility of the Delta variant, low vaccination coverage in several regions, and more relaxed attitude towards social distancing is expected to result in as surge in COVID-19 deaths in at least 40 states. In several states – including Idaho, Maine, Montana, Nebraska, North Carolina, Oregon, Puerto Rico, Washington, and West Virginia – the projected daily deaths in 2021 could exceed the prior peak daily deaths under current social distancing behavior and vaccination rate. The number of COVID-19 deaths across the U.S. could exceed 1600 per day.
Between August 1, 2021, and December 31, 2021, there could be additional 157,000 COVID-19 deaths across the U.S. Of note, our model projected approximately 20,700 COVID-19 deaths in Texas, 16,000 in California, 12,400 in Florida, 12,000 in North Carolina, and 9,300 in Georgia during this period. In contrast, the projected number of COVID-19 deaths would remain below 200 in New Jersey, Massachusetts, Connecticut, Vermont, and Rhode Island.
We project COVID-19 deaths based on the current vaccination rates and social distancing behavior. Our hope is that the findings of this report serve a warning sign and people revert to wearing masks and maintain social distancing to reduce COVID-19 associated deaths in the U.S. Our projections are updated weekly by incorporating vaccination rates and social distancing measures in each state; the latest results can be found at the COVID-19 Simulator website.
### Competing Interest Statement
This research is funded by the Rockefeller Foundation grant to support the work of the Society for Medical Decision Making COVID-19 Decision Modeling Initiative, and National Science Foundation awards 2035360 and 2035361. The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. Drs. Chhatwal and Ayer serve as partners of Value Analytics Labs, a healthcare analytics consulting firm that provides services to pharmaceutical and diagnostic companies.
### Funding Statement
This research is funded by the Rockefeller Foundation grant to support the work of the Society for Medical Decision Making COVID-19 Decision Modeling Initiative, and National Science Foundation awards 2035360 and 2035361.The funding agreement ensured the independence of authors in designing the study, interpreting the data, writing, and publishing the report.
### 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:
All data used in this study were publicly available and therefore did not require approval from an institutional review board
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Our model is available to the public at www.covid19sim.org and data can be downloaded from the website.
(PDF) Similar patterns of 18F-FDG brain PET hypometabolism in paediatric and adult patients with long COVID: a paediatric case series
PDF | Purpose. Several weeks after COVID-19 infection, some children report the persistence or recurrence of functional complaints. This clinical... | Find, read and cite all the research you need on ResearchGate
(3) Christian Fries auf Twitter: "Besteht wirklich so ein großer Unterschied zwischen Inzidenz 50 und 200? „Kinder unter 12 infizieren sich doch so oder so. Hauptsache die Intensivstation läuft nicht über.“ Ist das so? Eine kleine Rechnung zur Illustration: ⬇️ 1/9 #COVID19 #GrundrechenartenAmWochende" / Twitter
Besteht wirklich so ein großer Unterschied zwischen Inzidenz 50 und 200?
„Kinder unter 12 infizieren sich doch so oder so. Hauptsache die Intensivstation läuft nicht über.“
Ist das so? Eine kleine Rechnung zur Illustration: ⬇️
1/9 #COVID19 #GrundrechenartenAmWochende
ABSTRACTBackground:StartingDecember2020,IsraelbeganamassvaccinationcampaignagainstcoronavirusadministeringthePfizerBNT162b2vaccine,whichledtoasharpcurtailingoftheoutbreak.AfteraperiodwithalmostnoSARS-CoV-2infections,aresurgentCOVID-19outbreakinitiatedmidJune2021.PossiblereasonsforthebreakthroughwerereducedvaccineeffectivenessagainsttheDeltavariant,andwaningimmunity.TheaimofthisstudywastoquantifytheextentofwaningimmunityusingIsrael'snational-database.Methods:DataonallPCRpositivetestresultsbetweenJuly11-31,2021ofIsraeliresidentswhobecamefullyvaccinatedbeforeJune2021wereusedinthisanalysis.InfectionratesandsevereCOVID-19outcomeswerecomparedbetweenindividualswhowerevaccinatedindifferenttimeperiodsusingaPoisson regression, stratifying by age group and adjustingfor possible confounding factors.Results:TheratesofbothdocumentedSARS-CoV-2infectionsandsevereCOVID-19exhibitastatisticallysignificantincreaseastimefromsecondvaccinedoseelapsed.Elderlyindividuals(60+)whoreceivedtheirseconddoseinMarch2021were1.6(CI:[1.3,2])timesmoreprotectedagainstinfectionand1.7(CI:[1.0,2.7])timesmoreprotectedagainstsevereCOVID-19comparedtothosewhoreceivedtheir second dose in January 2021. Similar resultswere found for different age groups.Conclusions:Theseresultsindicateastrongeffectofwaningimmunityinallagegroupsaftersixmonths.Quantifyingtheeffectofwaningimmunityonvaccineeffectivenessiscriticalforpolicymakersworldwidefacing the dilemma of administering booster vaccinations.
Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers
Background SARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur.
Methods We analyzed the virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), using RT-PCR and virus culture.
Results The delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, we demonstrate lower probability of infectious virus detection in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness.
Conclusions We conclude that rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases.
### Competing Interest Statement
The authors have declared no competing interest.
### Funding Statement
No external funding
### 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:
This study was approved by Radboud university medical center Committee on Research Involving Human Subjects (CMO) and the Erasmus Medical Center Medical Ethics Committee (METC). All samples were collected following routine institutional COVID-19 testing guidelines, the participants were not subject to any procedures for the purpose of this study and all data were anonymized prior to analysis.
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data are available upon request
SARS-CoV-2 aerosol transmission in schools: the effectiveness of different interventions
Background Indoor aerosol transmission of SARS-CoV-2 has been widely recognized, especially in schools where children remain in close proximity and largely unvaccinated. Measures such as strategic natural ventilation and high efficiency particulate air (HEPA) filtration remain poorly implemented and mask mandates are often progressively lifted as vaccination rollout is enhanced.
Methods We adapted a previously developed aerosol transmission model to study the effect of interventions (natural ventilation, face masks, HEPA filtration, and their combinations) on the concentration of virus particles in a classroom of 160 m3 containing one infectious individual. The cumulative dose of viruses absorbed by exposed occupants was calculated.
Results The most effective single intervention was natural ventilation through the full opening of six windows all day during the winter (14-fold decrease in cumulative dose), followed by the universal use of surgical face masks (8-fold decrease). In the spring/summer, natural ventilation was only effective (≥ 2-fold decrease) when windows were fully open all day. In the winter, partly opening two windows all day or fully opening six windows at the end of each class was effective as well (≥ 2-fold decrease). Opening windows during yard and lunch breaks only had minimal effect (≤ 1.2-fold decrease). One HEPA filter was as effective as two windows partly open all day during the winter (2.5-fold decrease) while two filters were more effective (4-fold decrease). Combined interventions (i.e., natural ventilation, masks, and HEPA filtration) were the most effective (≥ 30-fold decrease). Combined interventions remained highly effective in the presence of a super-spreader.
Conclusions Natural ventilation, face masks, and HEPA filtration are effective interventions to reduce SARS-CoV-2 aerosol transmission. These measures should be combined and complemented by additional interventions (e.g., physical distancing, hygiene, testing, contact tracing, and vaccination) to maximize benefit.
### Competing Interest Statement
The authors have declared no competing interest.
### Funding Statement
OK was supported by the Swiss National Science Foundation (grants no 196270 and 163878).
### 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:
This research did not involve human or animal subjects, and ethical approval was therefore not required
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Access to the tool and model code can be obtained from the corresponding author.
Comparison of Neutralizing Antibody Titers Elicited by mRNA and Adenoviral Vector Vaccine against SARS-CoV-2 Variants
The increasing prevalence of SARS-CoV-2 variants has raised concerns regarding possible decreases in vaccine efficacy. Here, neutralizing antibody titers elicited by mRNA-based and an adenoviral vector-based vaccine against variant pseudotyped viruses were compared. BNT162b2 and mRNA-1273-elicited antibodies showed modest neutralization resistance against Beta, Delta, Delta plus and Lambda variants whereas Ad26.COV2.S-elicited antibodies from a significant fraction of vaccinated individuals were of low neutralizing titer (IC50