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Uncertain effects of the pandemic on respiratory viruses
Uncertain effects of the pandemic on respiratory viruses
The emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and subsequent mitigation measures have caused widespread social disruption. These disruptions have also affected community transmission of endemic diseases and the seasonal circulation patterns of other respiratory viruses. In both the Northern and Southern hemispheres, within-season influenza activity has been at historically low levels since 2020 ([ 1 ][1], [ 2 ][2]). Additionally, the circulation of human metapneumovirus, enterovirus, adenovirus, respiratory syncytial virus (RSV), and rhinovirus has been substantially reduced ([ 3 ][3]). These reductions in respiratory virus infections are linked to changes in health care–seeking behaviors and limited surveillance capacity, but mostly to the widespread implementation of nonpharmacological interventions (NPIs) to control SARS-CoV-2 transmission. How this will affect the transmission patterns of endemic respiratory viruses remains unknown. NPIs such as face mask use, increased handwashing practices, social distancing, and restrictions of global mobility have been key measures in reducing circulation of other respiratory viruses. As NPIs are relaxed and vaccination programs increase to control SARS-CoV-2 infections, countries have started to report increases in activity and circulation of certain viruses, such as RSV and rhinoviruses, with atypical timing ([ 3 ][3]–[ 6 ][4]). It is unclear why similar trends of resurgence (off-seasonal increases) have not been observed so far in other respiratory viruses, such as influenza, following relaxation of NPI measures. Currently, questions remain as to what the downstream impact of the COVID-19 pandemic and our response to it will be on circulation patterns of endemic respiratory viruses. What can be expected once this pandemic subsides and NPIs are lifted? If there is a reduction of population-level immunity, endemic respiratory viruses could resurge with atypical patterns and/or with high attack rates (higher risk of infection during a specific time period) owing to the large susceptible population. Current disruption in respiratory virus circulation could also lead to changes in their epidemiology—for example, changes in age distribution or disease severity. Moreover, it is unclear how many years it would take to reestablish regular seasonal patterns and whether new pandemic threats can be expected, especially considering the unpredictability of influenza virus evolution and the role of animal reservoirs (see the figure). Modeling studies have started to explore the impact of an increase in population susceptibility due to minimal RSV and influenza virus infections in 2020–2021 on the magnitude of subsequent seasons ([ 7 ][5]). RSV is a common respiratory virus that often circulates during cold months in temperate countries, causing mostly mild disease in the general population but with a risk for severe disease in infants and the elderly. Contrary to influenza viruses, RSV has no known animal reservoir. Two main antigenic groups (A and B) present variability that may contribute to the ability of RSV to establish reinfections throughout a life span. Data from surveillance systems have recently identified off-season circulation of RSV in both Northern and Southern hemispheres, albeit of lower magnitude than in previously documented RSV seasons and despite some NPIs still in use. This increased circulation could have been driven by an increased susceptibility in the very young and waning of immunity among adults ([ 5 ][6]). Periodic circulation of RSV, even if limited, may minimize the pool of susceptible population in the long term and prevent large outbreaks in the future ([ 6 ][4]). For influenza viruses, the overall modeling conclusions are less robust than for RSV ([ 7 ][5]). The rapid evolution and the dynamics of host immunity associated with influenza virus infections add further uncertainty and complexity to the modeling forecast. Although initial modeling analyses ([ 7 ][5]) help illustrate broad scenarios of the possible impact of the COVID-19 pandemic on endemic respiratory diseases, they also highlight the gaps in data and knowledge on viral interference theories (which explain how an individual infected by a virus becomes resistant to infection by a second virus), environmental and temperature effects on virus seasonality, and the role of immunity in transmission at the population level. Theoretically, in the case of influenza virus, limited community transmission, as documented in the last seasons, could present less opportunity for viral mutations ([ 8 ][7]) through antigenic drift (a process of gradual accumulation of mutations in the surface glycoproteins, or antigens, of the influenza virus). Overall, the lack of new mutation opportunities could limit the variability of circulating influenza viruses ([ 9 ][8], [ 10 ][9]). In turn, those viruses accumulating mutations could face limited antigenic selection due to a lower immunological pressure because there is a reduction in population-wide immunity, despite the increased influenza vaccination coverage observed in 2020 in various countries ([ 11 ][10]). The pool of susceptible individuals could also change qualitatively, with children becoming especially vulnerable during future influenza epidemics if the rest of the population maintains cross-protection from infection with previous seasonal strains. The implication of this scenario is the possibility of future (larger) influenza seasonal outbreaks affecting clinically different subpopulations. Nonetheless, if more homogeneous populations of viruses are observed, disease could be controlled through well-matched vaccines. Conversely, reduced population-wide immunity could allow for the emergence of variant strains with pandemic potential, including those possibly introduced from other species. This is observed, for example, with H3N2v viruses, which are often detected during summertime in the US from exposure to swine in agricultural fairs ([ 12 ][11]). These variant strains mostly affect children because population immunity from other H3N2 circulating viruses may be controlling their spread among the adult population ([ 13 ][12]). Further research into the underlying mechanisms determining the epidemiological features of specific respiratory viruses that considers viral evolution, interactions among viruses, and between virus and host immunity is needed. This will help identify emerging pandemic threats as well as better prepare for the long-term management of future outbreaks and epidemics. The evolution of SARS-CoV-2 and the appearance of variants threatening the effectiveness of newly authorized vaccines have underlined the importance and limitations of genomic surveillance networks globally. The uncertainty in future scenarios for other respiratory viruses in the post–COVID-19 period, including possible surges off-season and changes in clinical burden distribution, raises the need for an improved and comprehensive approach to respiratory disease and viral genomic surveillance. Widespread virus genomic surveillance embedded as part of national disease surveillance efforts and with links to clinical and epidemiological data could not only help monitor evolution but also identify those changes in strains associated with increased disease severity or vaccine breakthrough. It could improve current and new vaccine targets by refining vaccine strain selection against COVID-19 and influenza. ![Figure][13] Patterns of respiratory virus infections During the pandemic, circulation patterns of respiratory viruses other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been disrupted. This could mean a future shift in the epidemiology of respiratory diseases, potential for new epidemic threats, or larger outbreaks than previously observed. It is also unknown how long it will take for seasonal circulation patterns to return to prepandemic levels. Graphs illustrate trends in detection of respiratory viruses. Data are from respiratory illness surveillance in participating sites of the Global Influenza Hospital Surveillance Network ([ 14 ][14]). GRAPHIC: N. DESAI/ SCIENCE The COVID-19 pandemic has exposed the extent to which countries are still ill-prepared to monitor the emergence of new viruses, to assess their potential public health risk and the effectiveness of public health responses. The World Health Organization's Global Influenza Surveillance and Response System (GISRS) network, though providing much needed surveillance coverage, has limited linkages to clinical data, and global hospital-based surveillance networks once heavily supported by the US Centers for Disease Control and Prevention have suffered from disinvestments in recent years. Ensuring effective and real-time data sharing, expanding geographical coverage, and integrating genomic data of identified viruses with clinical data will require dedicated financing mechanisms and a stronger scientific collaboration between diagnostic and pharmaceutical companies, public health authorities, and academic institutions. The Global Influenza Hospital Surveillance Network (GIHSN) has provided a proof of concept for the expansion of current systems ([ 14 ][14]). This public-private partnership initiative was built 8 years ago to improve surveillance of influenza viruses and covers more than 100 hospitals across over 20 countries. Centers are asked to identify episodes of severe acute respiratory illness among hospitalized patients, testing primarily for influenza virus but covering other selected respiratory viruses, such as SARS-CoV-2, as resources allow. The network then ensures that virus whole-genome sequencing data are linked to epidemiologic and clinical data. The genomic sequences are uploaded into GISAID, a global data-sharing platform that has become the largest database of SARS-CoV-2 genomic data ([ 15 ][15]). These i
·science.sciencemag.org·
Uncertain effects of the pandemic on respiratory viruses
(2) Eric Feigl-Ding auf Twitter: "2) We are expecting the #DeltaVariant to continue growing in the US, outpacing all other variants just like it has in India 🇮🇳 and UK 🇬🇧, and become dominant in US by end of July, if not earlier. Here is the prediction track - via @TWenseleers from @GISAID data. https://t.co/VRWL9abxZd" / Twitter
(2) Eric Feigl-Ding auf Twitter: "2) We are expecting the #DeltaVariant to continue growing in the US, outpacing all other variants just like it has in India 🇮🇳 and UK 🇬🇧, and become dominant in US by end of July, if not earlier. Here is the prediction track - via @TWenseleers from @GISAID data. https://t.co/VRWL9abxZd" / Twitter
2) We are expecting the #DeltaVariant to continue growing in the US, outpacing all other variants just like it has in India 🇮🇳 and UK 🇬🇧, and become dominant in US by end of July, if not earlier. Here is the prediction track - via @TWenseleers from @GISAID data. https://t.co/VRWL9abxZd
·twitter.com·
(2) Eric Feigl-Ding auf Twitter: "2) We are expecting the #DeltaVariant to continue growing in the US, outpacing all other variants just like it has in India 🇮🇳 and UK 🇬🇧, and become dominant in US by end of July, if not earlier. Here is the prediction track - via @TWenseleers from @GISAID data. https://t.co/VRWL9abxZd" / Twitter
The Fail West
The Fail West
They Knew. They Ignored. The Reckoning, One Year In. Welcome to the first article of Uncharted Territories! In the next few ones, we’re going to draw lessons from the last year of the pandemic while I start introducing new topics I’m very excited about! For example, there’s an in-depth look at remote work, and another one about how everything you’ve ever been told about History is false. Through the regular articles, I’ll make sure you get a good sense for the premium ones. And, as always, all articles related to the management of COVID will be free. For today, we’re going to expose the failures, expose the excuses, expose the lies, expose what we knew one year ago that we didn’t learn fast enough, and the true reasons why the West failed. If you are receiving this from a friend, feel free to subscribe!
·unchartedterritories.tomaspueyo.com·
The Fail West
outbreak.info
outbreak.info
Concerns surrounding new strains of SARS-CoV-2 (hCoV-19), the virus behind the COVID-19 pandemic, have been developing. This report outlines the prevalence of the B.1.617.2 lineage in the world, how it is changing over time, and how its prevalence varies across different locations.
·outbreak.info·
outbreak.info
The World Mortality Dataset: Tracking excess mortality across countries during the COVID-19 pandemic
The World Mortality Dataset: Tracking excess mortality across countries during the COVID-19 pandemic
Comparing the impact of the COVID-19 pandemic between countries or across time is difficult because the reported numbers of cases and deaths can be strongly affected by testing capacity and reporting policy. Excess mortality, defined as the increase in all-cause mortality relative to the expected mortality, is widely considered as a more objective indicator of the COVID-19 death toll. However, there has been no global, frequently-updated repository of the all-cause mortality data across countries. To fill this gap, we have collected weekly, monthly, or quarterly all-cause mortality data from 94 countries and territories, openly available as the regularly-updated World Mortality Dataset. We used this dataset to compute the excess mortality in each country during the COVID-19 pandemic. We found that in several worst-affected countries (Peru, Ecuador, Bolivia, Mexico) the excess mortality was above 50% of the expected annual mortality. At the same time, in several other countries (Australia, New Zealand) mortality during the pandemic was below the usual level, presumably due to social distancing measures decreasing the non-COVID infectious mortality. Furthermore, we found that while many countries have been reporting the COVID-19 deaths very accurately, some countries have been substantially underreporting their COVID-19 deaths (e.g. Nicaragua, Russia, Uzbekistan), sometimes by two orders of magnitude (Tajikistan). Our results highlight the importance of open and rapid all-cause mortality reporting for pandemic monitoring. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement DK was supported by the Deutsche Forschungsgemeinschaft (BE5601/4-1 and the Cluster of Excellence "Machine Learning \---| New Perspectives for Science", EXC 2064, project number 390727645), the Federal Ministry of Education and Research (FKZ 01GQ1601 and 01IS18039A) and the National Institute of Mental Health of the National Institutes of Health under Award Number U19MH114830. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ### 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: Non 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 The dataset is available at https://github.com/akarlinsky/world_mortality The analysis code is available at https://github.com/dkobak/excess-mortality
·medrxiv.org·
The World Mortality Dataset: Tracking excess mortality across countries during the COVID-19 pandemic
Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact
Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact
Growing evidence shows that a significant number of patients with COVID-19 experience prolonged symptoms, known as Long COVID. Few systematic studies exist which investigate this population, and hence, relatively little is known about the range in symptom makeup and severity, expected clinical course, impact on daily functioning, and expected return to baseline health. In this study, we analysed responses from 3,762 participants with confirmed (diagnostic/antibody positive; 1,020) or suspected (diagnostic/antibody negative or untested; 2,742) COVID-19, from 56 countries, with illness duration of at least 28 days. 3608 (96%) reported symptoms beyond 90 days. Prevalence of 205 symptoms in 10 organ systems was estimated in this cohort, with 66 symptoms traced over seven months. Except for loss of smell and taste, the prevalence and trajectory of all symptoms were similar between groups with confirmed and suspected COVID-19. Respondents experienced an average of 14.5 symptoms in an average of 9.08 organ systems. Three clusters of symptoms were identified based on their prevalence over time. The most likely early symptoms were fatigue, dry cough, shortness of breath, headaches, muscle aches, chest tightness, and sore throat. The most frequent symptoms reported after month 6 were fatigue, post-exertional malaise, and cognitive dysfunction. Majority (>85%) experienced relapses, with exercise, physical or mental activity, and stress as the main triggers. 1,700 (45.2%) reported requiring a reduced work schedule compared to pre-illness and 839 (22.3%) were not working at the time of survey due to their health conditions. Significance Statement Results from our international online survey of 3,762 individuals with suspected or confirmed COVID-19 illness suggest that Long COVID is composed of heterogeneous post-acute infection sequelae that often affect multiple organ systems, with impact on functioning and quality of life ranging from mild to severe. This study represents the largest collection of symptoms identified in the Long COVID population to date, and is the first to quantify individual symptom trajectory over time, for 7 months. Three clusters of symptoms were quantified, each with different morphologies over time. The clusters of symptoms that persist longest include a combination of the neurological/cognitive and systemic symptoms. The reduced work capacity because of cognitive dysfunction, in addition to other debilitating symptoms, translated into the loss of hours, jobs, and ability to work relative to pre-illness levels. Objective To characterize the symptom profile and time course in patients with Long COVID, along with the impact on daily life, work, and return to baseline health. Design International web-based survey of suspected and confirmed COVID-19 cases with illness lasting over 28 days and onset prior to June 2020. Setting Survey distribution via online COVID-19 support groups and social media Participants 3,762 respondents from 56 countries completed the survey. 1166 (31.0%) were 40-49 years old, 937 (25.0%) were 50-59 years old, 905 (24.1%) were 30-39 years old, 277 (7.4%) were 18-29 years old, and 477 (12.7%) were above 60 years old. 2961 (78.9%) were women, 718 (19.1%) were men, and 63 (1.7%) were nonbinary. 317 (8.4%) reported being hospitalized. 1020 (27.1%) reported receiving a laboratory-confirmed diagnosis of COVID-19. 3608 (96%) reported symptoms beyond 90 days. Results Prevalence of 205 symptoms in 10 organ systems was estimated in this cohort, with 66 symptoms traced over seven months. Except for loss of smell and taste, the prevalence and trajectory of all other symptoms are similar between confirmed (diagnostic/antibody positive) and suspected groups (diagnostic/antibody negative or untested). Respondents experienced symptoms in an average of 9.08 (95% confidence interval 9.04 to 9.13) organ systems. The most frequent symptoms reported after month 6 were: fatigue (77.7%, 74.9% to 80.3%), post-exertional malaise (72.2%, 69.3% to 75.0%), and cognitive dysfunction (55.4%, 52.4% to 58.8%). These three symptoms were also the three most commonly reported overall. In those who recovered in less than 90 days, the average number of symptoms peaked at week 2 (11.4, 9.4 to 13.6), and in those who did not recover in 90 days, the average number of symptoms peaked at month 2 (17.2, 16.5 to 17.8). Respondents with symptoms over 6 months experienced an average of 13.8 (12.7 to 14.9) symptoms in month 7. 85.9% (84.8% to 87.0%) experienced relapses, with exercise, physical or mental activity, and stress as the main triggers. 86.7% (85.6% to 92.5%) of unrecovered respondents were experiencing fatigue at the time of survey, compared to 44.7% (38.5% to 50.5%) of recovered respondents. 45.2% (42.9% to 47.2%) reported requiring a reduced work schedule compared to pre-illness and 22.3% (20.5% to 24.3%) were not working at the time of survey due to their health conditions. Conclusions Patients with Long COVID report prolonged multisystem involvement and significant disability. Most had not returned to previous levels of work by 6 months. Many patients are not recovered by 7 months, and continue to experience significant symptom burden. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Authors are group of volunteers. Survey expenses were covered by AA's research fund from Sainsbury Wellcome Centre (Wellcome Trust and Gatsby Charity). Some donations to Patient-Led Research for COVID-19 were directed towards graphic design work. ### 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 the UCL Research Ethics Committee [16159.002], and Oregon Health and Science University, Portland, Oregon, USA, with UCL serving as primary site. Weill Cornell Medical College Institutional Review Board (IRB) exemption was obtained. All participants gave 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 Based on the UCL Ethics Approval, the raw data cannot be shared publicly. However, anonymised data will become available to all interested parties, after the publication.
·medrxiv.org·
Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact
Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact
Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact
Objective To characterize the symptom profile and time course in patients with Long COVID, along with the impact on daily life, work, and return to baseline health. Design International web-based survey of suspected and confirmed COVID-19 cases with illness lasting over 28 days and onset prior to June 2020. Setting Survey distribution via online COVID-19 support groups and social media Participants 3,762 respondents from 56 countries completed the survey. 1166 (33.7%) were 40-49 years old, 937 (27.1%) were 50-59 years old, and 905 (26.1%) were 30-39 years old. 2961 (78.9%) were women, 718 (19.1%) were men, and 63 (1.7%) were nonbinary. 8.4% reported being hospitalized. 27% reported receiving a laboratory-confirmed diagnosis of COVID-19. 96% reported symptoms beyond 90 days. Results Prevalence of 205 symptoms in 10 organ systems was estimated in this cohort, with 66 symptoms traced over seven months. Respondents experienced symptoms in an average of 9.08 (95% confidence interval 9.04 to 9.13) organ systems. The most frequent symptoms reported after month 6 were: fatigue (77.7%, 74.9% to 80.3%), post-exertional malaise (72.2%, 69.3% to 75.0%), and cognitive dysfunction (55.4%, 52.4% to 58.8%). These three symptoms were also the three most commonly reported overall. In those who recovered in less than 90 days, the average number of symptoms peaked at week 2 (11.4, 9.4 to 13.6), and in those who did not recover in 90 days, the average number of symptoms peaked at month 2 (17.2, 16.5 to 17.8). Respondents with symptoms over 6 months experienced an average of 13.8 (12.7 to 14.9) symptoms in month 7. 85.9% (84.8% to 87.0%) experienced relapses, with exercise, physical or mental activity, and stress as the main triggers. 86.7% (85.6% to 92.5%) of unrecovered respondents were experiencing fatigue at the time of survey, compared to 44.7% (38.5% to 50.5%) of recovered respondents. 45.2% (42.9% to 47.2%) reported requiring a reduced work schedule compared to pre-illness and 22.3% (20.5% to 24.3%) were not working at the time of survey due to their health conditions. Conclusions Patients with Long COVID report prolonged multisystem involvement and significant disability. Most had not returned to previous levels of work by 6 months. Many patients are not recovered by 7 months, and continue to experience significant symptom burden. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Authors are group of volunteers. Survey expenses were covered by AA's research fund from Sainsbury Wellcome Centre (Wellcome Trust and Gatsby Charity). Some donations to Patient-Led Research for COVID-19 were directed towards graphic design work. ### 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 the UCL Research Ethics Committee [16159.002], and Oregon Health and Science University, Portland, Oregon, USA, with UCL serving as primary site. Weill Cornell Medical College Institutional Review Board (IRB) exemption was obtained. All participants gave 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 Based on the UCL Ethics Approval, the raw data cannot be shared publicly. However, anonymised data will become available to all interested parties, after the publication.
·medrxiv.org·
Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact
The Lancet auf Twitter: "NEW—Correspondence reports initial analysis of neutralising antibody activity against #SARS-CoV-2 variants of concern B.1.617.2 and B.1.351 elicited by partial or full vaccination with #BNT162b2 (#Pfizer-BioNTech). Read https://t.co/mW69kw1jCh. Figure from appendix. @TheCrick https://t.co/3rTI65ckg7" / Twitter
The Lancet auf Twitter: "NEW—Correspondence reports initial analysis of neutralising antibody activity against #SARS-CoV-2 variants of concern B.1.617.2 and B.1.351 elicited by partial or full vaccination with #BNT162b2 (#Pfizer-BioNTech). Read https://t.co/mW69kw1jCh. Figure from appendix. @TheCrick https://t.co/3rTI65ckg7" / Twitter
NEW—Correspondence reports initial analysis of neutralising antibody activity against #SARS-CoV-2 variants of concern B.1.617.2 and B.1.351 elicited by partial or full vaccination with #BNT162b2 (#Pfizer-BioNTech). Read https://t.co/mW69kw1jCh. Figure from appendix. @TheCrick https://t.co/3rTI65ckg7
·twitter.com·
The Lancet auf Twitter: "NEW—Correspondence reports initial analysis of neutralising antibody activity against #SARS-CoV-2 variants of concern B.1.617.2 and B.1.351 elicited by partial or full vaccination with #BNT162b2 (#Pfizer-BioNTech). Read https://t.co/mW69kw1jCh. Figure from appendix. @TheCrick https://t.co/3rTI65ckg7" / Twitter
Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection | Nature Medicine
Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection | Nature Medicine
Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.
·nature.com·
Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection | Nature Medicine
Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination
Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination
The SARS-CoV-2 B.1.617.2 Variant of Concern (VOC), first detected in India, is now dominant in the UK, having rapidly1 displaced the B.1.1.7 strain2 that emerged in the UK with the second COVID-19 wave in late 2020. The efficacy of currently licensed COVID-19 vaccines against B.1.617.2 is unknown; although it possesses 12 mutations in its spike protein relative to the wildtype SARS-CoV-2 first detected in Wuhan, China, in December, 2019, B.1.617.2 lacks mutations at amino acid positions 501 or 484 in its ACE2 receptor-binding domain, commonly associated with VOCs (appendix p 2) or escape from neutralising antibodies (NAbs).
·thelancet.com·
Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination
(7) Michael Lin, PhD-MD auf Twitter: "Antibodies elicited by the Pfizer/BioNTech RNA vax are 6x less potent in neutralizing B.1.617 (delta variant that devastated India). This lowers predicted efficacy for symptomatic COVID19 to ~70%. This compares to 2x drop in neutralizing activity for Covaxin. I discuss in 🧵" / Twitter
(7) Michael Lin, PhD-MD auf Twitter: "Antibodies elicited by the Pfizer/BioNTech RNA vax are 6x less potent in neutralizing B.1.617 (delta variant that devastated India). This lowers predicted efficacy for symptomatic COVID19 to ~70%. This compares to 2x drop in neutralizing activity for Covaxin. I discuss in 🧵" / Twitter
Antibodies elicited by the Pfizer/BioNTech RNA vax are 6x less potent in neutralizing B.1.617 (delta variant that devastated India). This lowers predicted efficacy for symptomatic COVID19 to ~70%. This compares to 2x drop in neutralizing activity for Covaxin. I discuss in 🧵
·twitter.com·
(7) Michael Lin, PhD-MD auf Twitter: "Antibodies elicited by the Pfizer/BioNTech RNA vax are 6x less potent in neutralizing B.1.617 (delta variant that devastated India). This lowers predicted efficacy for symptomatic COVID19 to ~70%. This compares to 2x drop in neutralizing activity for Covaxin. I discuss in 🧵" / Twitter
Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data
Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data
Two doses of BNT162b2 are highly effective across all age groups (≥16 years, including older adults aged ≥85 years) in preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations, severe disease, and death, including those caused by the B.1.1.7 SARS-CoV-2 variant. There were marked and sustained declines in SARS-CoV-2 incidence corresponding to increasing vaccine coverage. These findings suggest that COVID-19 vaccination can help to control the pandemic.
·thelancet.com·
Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data
The COVID-19 pandemic as experienced by theindividual
The COVID-19 pandemic as experienced by theindividual
The COVID-19 pandemic as experienced by theindividualPatrick Garland∗Dave Babbitt†Maksym Bondarenko‡Alessandro Sorichetta§Andrew J. Tatem¶Oliver Johnson‖September 30, 2020AbstractThe ongoing COVID-19 pandemic has progressed with varying degrees of intensityin individual countries, suggesting it is important to analyse factors that vary betweenthem. We study measures of ‘population-weighted density’, which capture densityas perceived by a randomly chosen individual. These measures of population densitycan significantly explain variation in the initial rate of spread of COVID-19 betweencountries within Europe. However, such measures do not explain differences on aglobal scale, particularly when considering countries in East Asia, or looking laterinto the epidemics. Therefore, to control for country-level differences in responseto COVID-19 we consider the cross-cultural measure of individualism proposed byHofstede. This score can significantly explain variation in the size of epidemics acrossEurope, North America, and East Asia. Using both our measure of population-weighted density and the Hofstede score we can significantly explain half the variationin the current size of epidemics across Europe and North America. By controllingfor country-level responses to the virus and population density, our analysis of theglobal incidence of COVID-19 can help focus attention on epidemic control measuresthat are effective for individual countries.
·arxiv.org·
The COVID-19 pandemic as experienced by theindividual
Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity
Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity
Background Heterologous prime-boost schedules with vector- and mRNA-based COVID-19 vaccines are already administered, but immunological responses and elicited protection have not been reported. Methods We here analyzed a cohort of 26 individuals aged 25-46 (median 30.5) years that received a ChAdOx1 nCoV-2019 prime followed by a BNT162b2 boost after an 8-week interval for reactogenicity, antibody responses and T cell reactivity. Results Self-reported solicited symptoms after ChAdOx1 nCoV-2019 prime were in line with previous reports and less severe after the BNT162b2 boost. Antibody titers increased significantly over time resulting in strong neutralization titers 2 weeks after the BNT162b2 boost. Neutralizing activity against the prevalent strain B.1.1.7 was 3.9-fold higher than in individuals receiving homologous BNT162b2 vaccination, only 2-fold reduced for variant of concern B.1.351, and similar for variant B.1.617. In addition, CD4+ and CD8+ T cells reacted to SARS-CoV-2 spike peptide stimulus 2 weeks after the full vaccination. Conclusions The heterologous ChAdOx1 nCoV-2019 / BNT162b2 prime-boost vaccination regimen is not associated with serious adverse events and results in a potent humoral immune response and elicits T cell reactivity. Variants of concern B.1.1.7, B.1.351 and B.1.617 are potently neutralized by sera of all participants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project has received funding from the European Union Horizon 2020 research and innovation programme, the German Research Foundation, the BMBF, the Robert Koch Institute, the Baden-Wuerttemberg Stiftung, the Ministry for Science, Research and the Arts of Baden-Wuerttemberg and the county of Lower Saxony. ### 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 the ethics committee of Ulm university (99/21; 31/21). 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 is available upon request after positive peer-review evaluation.
·medrxiv.org·
Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity
Rüdiger Groß auf Twitter: "Our preprint on heterologous COVID-19 vaccination is out! We report reactogenicity & immunogenicity (antibodies, T cells) after AZ prime and BNT/Pfizer boost with an 8w interval; compare antibody levels to a cohort with 2x BNT vaccination. (1/8) 🧵 https://t.co/hKwGANbiyg" / Twitter
Rüdiger Groß auf Twitter: "Our preprint on heterologous COVID-19 vaccination is out! We report reactogenicity & immunogenicity (antibodies, T cells) after AZ prime and BNT/Pfizer boost with an 8w interval; compare antibody levels to a cohort with 2x BNT vaccination. (1/8) 🧵 https://t.co/hKwGANbiyg" / Twitter
Our preprint on heterologous COVID-19 vaccination is out! We report reactogenicity & immunogenicity (antibodies, T cells) after AZ prime and BNT/Pfizer boost with an 8w interval; compare antibody levels to a cohort with 2x BNT vaccination. (1/8) 🧵 https://t.co/hKwGANbiyg
·twitter.com·
Rüdiger Groß auf Twitter: "Our preprint on heterologous COVID-19 vaccination is out! We report reactogenicity & immunogenicity (antibodies, T cells) after AZ prime and BNT/Pfizer boost with an 8w interval; compare antibody levels to a cohort with 2x BNT vaccination. (1/8) 🧵 https://t.co/hKwGANbiyg" / Twitter
InI4🌍 Spread Ideas Not Viruses, hat einen Schuss auf Twitter: "Wichtiger als Kinder durchimpfen wäre mir doch wieder #NoCovid/#LowCovid. Zumal wir auch Mitmenschen allen Alters haben, die man nicht oder nicht wirksam impfen kann." / Twitter
InI4🌍 Spread Ideas Not Viruses, hat einen Schuss auf Twitter: "Wichtiger als Kinder durchimpfen wäre mir doch wieder #NoCovid/#LowCovid. Zumal wir auch Mitmenschen allen Alters haben, die man nicht oder nicht wirksam impfen kann." / Twitter
Wichtiger als Kinder durchimpfen wäre mir doch wieder #NoCovid/#LowCovid. Zumal wir auch Mitmenschen allen Alters haben, die man nicht oder nicht wirksam impfen kann.
·twitter.com·
InI4🌍 Spread Ideas Not Viruses, hat einen Schuss auf Twitter: "Wichtiger als Kinder durchimpfen wäre mir doch wieder #NoCovid/#LowCovid. Zumal wir auch Mitmenschen allen Alters haben, die man nicht oder nicht wirksam impfen kann." / Twitter
Extended interval BNT162b2 vaccination enhances peak antibody generation in older people
Extended interval BNT162b2 vaccination enhances peak antibody generation in older people
Objectives To assess the relative immunogenicity of standard or extended interval BNT162b2 vaccination. Design Population based cohort study comparing immune responses 2 weeks after the second vaccine, with appropriate time-matched samples in participants who received standard or extended interval double vaccination. Setting Primary care networks, Birmingham, UK. December 2020 to April 2021. Participants 172 people aged over 80 years of age. All donors received the BNT162b2 Pfizer/BioNTech vaccination and were vaccinated with either a standard 3 week interval between doses or an extended interval schedule. Main outcome measures Peak quantitative spike-specific antibody and cellular immune responses. Results In donors without evidence of previous infection the peak antibody response was 3.5-fold higher in donors who had undergone delayed interval vaccination. Cellular immune responses were 3.6-fold lower. Conclusion Peak antibody responses after the second BNT162b2 vaccine are markedly enhanced in older people when this is delayed to 12 weeks although cellular responses are lower. Extended interval vaccination may therefore offer the potential to enhance and extend humoral immunity. Further follow up is now required to assess long term immunity and clinical protection. What is already known on this topic The BNT162b2 vaccine is highly effective against Covid-19 infection and was delivered with a 3-week time interval in registration studies. However, this interval has been extended in many countries in order to extend population coverage with a single vaccine. It is not known how immune responses after the second dose are influenced by delaying the second vaccine. What this study adds We provide the first assessment of immune responses in the first 14 weeks after standard or extended interval BNT162b2 vaccination and show that delaying the second dose acts to strongly boost the peak antibody response in older people. The extended interval vaccination may offer a longer period of clinical protection. This information will be of value in optimizing vaccine regimens and help guide guide vaccination policies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme. Ethical Approval: The work was performed under the CIA UPH IRAS approval (REC 20\NW\0240) and conducted according to the Declaration of Helsinki and good clinical practice. ### 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: Ethical approval was obtained from North West Preston Research Ethics Committee with favourable outcome and approval (REC 20\NW\0240). 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 Authors agree to share the anonymised raw data for this study once published.
·medrxiv.org·
Extended interval BNT162b2 vaccination enhances peak antibody generation in older people
Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals
Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals
The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India[1][1]–[6][2]. It has since then become dominant in some indian regions and further spread to many countries. The lineage includes three main subtypes (B1.617.1, B.1617.2 and B.1.617.3), which harbour diverse Spike mutations in the N-terminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2 is believed to spread faster than the other versions. Here, we isolated infectious B.1.617.2 from a traveller returning from India. We examined its sensitivity to monoclonal antibodies (mAbs) and to antibodies present in sera from COVID-19 convalescent individuals or vaccine recipients, in comparison to other viral lineages. B.1.617.2 was resistant to neutralization by some anti-NTD and anti-RBD mAbs, including Bamlanivimab, which were impaired in binding to the B.1.617.2 Spike. Sera from convalescent patients collected up to 12 months post symptoms and from Pfizer Comirnaty vaccine recipients were 3 to 6 fold less potent against B.1.617.2, relative to B.1.1.7. Sera from individuals having received one dose of AstraZeneca Vaxzevria barely inhibited B.1.617.2. Thus, B.1.617.2 spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes. ### Competing Interest Statement C.P., H.M., O.S, T.B., F.R. have a pending patent application for the anti-RBD mAbs described in the present study (PCT/FR2021/070522). [1]: #ref-1 [2]: #ref-6
·biorxiv.org·
Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals
The indirect effect of mRNA-based Covid-19 vaccination on unvaccinated household members
The indirect effect of mRNA-based Covid-19 vaccination on unvaccinated household members
Abstract: This paper studies the direct and indirect effectiveness of Covid-19 vaccines among vaccinated healthcare workers and their unvaccinated adult household members in a mass vaccine program in Finland. Methods: We used national databases that record all polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infections and mRNA-based (BNT162b2 by Pfizer-BioNTech or mRNA-1273 by Moderna) vaccine doses administered in Finland since the beginning of the epidemic. These data were merged with administrative full population datasets that include information on each person's occupation and unique identifiers for spouses living in the same household. To estimate the direct and indirect effectiveness of mRNA-based vaccines in a household setting, we compared the cumulative incidence of PCR-confirmed SARS-CoV-2 infections between vaccinated and unvaccinated healthcare workers as well as between their unvaccinated spouses. Findings: Our estimates imply indirect effectiveness of 8.7% (95% CI: -28.9 to 35.4) two weeks and 42.9% (95% CI: 22.3 to 58.1) 10 weeks after the first dose. The effectiveness estimates for unvaccinated household members are substantial, but smaller than the direct effect and occur more gradually among unvaccinated household members than among vaccinated individuals. Interpretation: Our results suggest that mRNA-based vaccines do not only prevent SARS-CoV-2 infections among vaccinated individuals but lead to a substantial reduction in infections among unvaccinated household members. The results are consistent with the notion that mRNA-based vaccines affect susceptibility in vaccinated individuals and prevent transmission from vaccinated to unvaccinated individuals. ### Competing Interest Statement Dr. Kortelainen declares grant to his employer, but no personal support or financial relationship, from Pfizer during the conduct of the study. Other authors have no conflict of interest to declare. ### Funding Statement This research was supported by the InFLAMES and INVEST Flagship Programmes of the Academy of Finland. Dr. Kortelainen declares grant to his employer, but no personal support or financial relationship, from Pfizer during the conduct of the study. Other authors have no conflict of interest to declare. ### 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 final data provided to the authors was de-identified. The research does not constitute human subjects research. Ethical approval was waived by the Institutional Review Board of the Finnish Institute for Health and Welfare (IRB: 00007085). 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 This paper uses administrative health care and employment data maintained by the Finnish Institute for Health and Welfare and Statistics Finland. Health care data is regulated under the Act on the Secondary Use of Health and Social Data (552/2019) and can be obtained by sending a direct request to the Finnish Institute for Health and Welfare (https://thl.fi/en). The Finnish Longitudinal Employer-Employee Data (FOLK) can be obtained by sending a direct request to Statistics Finland (https://www.stat.fi). The authors are willing to assist in making data access requests.
·medrxiv.org·
The indirect effect of mRNA-based Covid-19 vaccination on unvaccinated household members
Host Proteins Identified in Extracellular Viral Particles as Targets for Broad-Spectrum Antiviral Inhibitors
Host Proteins Identified in Extracellular Viral Particles as Targets for Broad-Spectrum Antiviral Inhibitors
Liquid chromatography mass spectrometry (LCMS) proteomic analyses have revealed that host proteins are often captured in extracellular virions. These proteins may play a role in viral replication or infectivity and can represent targets for broad-spectrum antiviral agent development. We utilized LCMS to determine the host protein composition of Lassa virus-like particles (LASV VLPs). Multiple host proteins incorporated in LASV VLPs are also incorporated in unrelated viruses, notably ribosomal proteins. We assembled a data set of host proteins incorporated into extracellular viral particles. The frequent incorporation of specific host proteins into viruses of diverse families suggests that interactions of these proteins with viral factors may be important for effective viral replication. Drugs that target virion-associated host proteins could affect the protein in the extracellular virion or the host cell. Compounds that target proteins incorporated into virions with high frequency, but with no known antiviral activity, were assayed in a scalable viral screening platform, and hits were tested in competent viral systems. One of these molecules, GAPDH modulating small molecule CGP 3466B maleate (Omigapil), exhibited a dose-dependent inhibition of HIV, dengue virus, and Zika virus.
·pubs.acs.org·
Host Proteins Identified in Extracellular Viral Particles as Targets for Broad-Spectrum Antiviral Inhibitors
Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals
Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals
The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India. It has since then become dominant in some indian regions and further spread to many countries. The lineage includes three main subtypes (B1.617.1, B.1617.2 and B.1.617.3), which harbour diverse Spike mutations in the N-terminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2 is believed to spread faster than the other versions. Here, we isolated infectious B.1.617.2 from a traveller returning from India. We examined its sensitivity to monoclonal antibodies (mAbs) and to antibodies present in sera from COVID-19 convalescent individuals or vaccine recipients, in comparison to other viral lineages. B.1.617.2 was resistant to neutralization by some anti-NTD and anti-RBD mAbs, including Bamlanivimab, which were impaired in binding to the B.1.617.2 Spike. Sera from convalescent patients collected up to 12 months post symptoms and from Pfizer Comirnaty vaccine recipients were 3 to 6 fold less potent against B.1.617.2, relative to B.1.1.7. Sera from individuals having received one dose of AstraZeneca Vaxzevria barely inhibited B.1.617.2. Thus, B.1.617.2 spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes. ### Competing Interest Statement C.P., H.M., O.S, T.B., F.R. have a pending patent application for the anti-RBD mAbs described in the present study (PCT/FR2021/070522).
·biorxiv.org·
Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals