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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
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
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
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
How Did We Get Here: What Are Droplets and Aerosols and How Far Do They Go? A Historical Perspective on the Transmission of Respiratory Infectious Diseases by Katherine Randall, E. Thomas Ewing, Linsey Marr, Jose Jimenez, L. Bourouiba :: SSRN
How Did We Get Here: What Are Droplets and Aerosols and How Far Do They Go? A Historical Perspective on the Transmission of Respiratory Infectious Diseases by Katherine Randall, E. Thomas Ewing, Linsey Marr, Jose Jimenez, L. Bourouiba :: SSRN
The COVID-19 pandemic has exposed major gaps in our understanding of the transmission of viruses through the air. These gaps slowed recognition of airborne tran
·papers.ssrn.com·
How Did We Get Here: What Are Droplets and Aerosols and How Far Do They Go? A Historical Perspective on the Transmission of Respiratory Infectious Diseases by Katherine Randall, E. Thomas Ewing, Linsey Marr, Jose Jimenez, L. Bourouiba :: SSRN
Estimating infectiousness throughout SARS-CoV-2 infection course
Estimating infectiousness throughout SARS-CoV-2 infection course
Two elementary parameters for quantifying viral infection and shedding are viral load and whether samples yield a replicating virus isolate in cell culture. We examined 25,381 German SARS-CoV-2 cases, including 6110 from test centres attended by pre-symptomatic, asymptomatic, and mildly-symptomatic (PAMS) subjects, 9519 who were hospitalised, and 1533 B.1.1.7 lineage infections. The youngest had mean log10 viral load 0.5 (or less) lower than older subjects and an estimated ~78% of the peak cell culture replication probability, due in part to smaller swab sizes and unlikely to be clinically relevant. Viral loads above 109 copies per swab were found in 8% of subjects, one-third of whom were PAMS, with mean age 37.6. We estimate 4.3 days from onset of shedding to peak viral load (8.1) and cell culture isolation probability (0.75). B.1.1.7 subjects had mean log10 viral load 1.05 higher than non-B.1.1.7, with estimated cell culture replication probability 2.6 times higher.
·science.sciencemag.org·
Estimating infectiousness throughout SARS-CoV-2 infection course
The impact of COVID-19 nonpharmaceutical interventions on the future dynamics of endemic infections
The impact of COVID-19 nonpharmaceutical interventions on the future dynamics of endemic infections
Nonpharmaceutical interventions (NPIs), such as social distancing, reduce not only COVID-19 cases but also other circulating infections such as influenza and RSV. The susceptible population for these infections will increase while NPIs are in place. Using models fit to historic cases of RSV and influenza, we project large future outbreaks of both diseases may occur following a period of extended NPIs. These outbreaks, which may reach peak numbers in the winter, could increase the burden to healthcare systems. Data for this study come from publicly available datasets. Code and collated data to recreate the main results are available via GitHub at .
·pnas.org·
The impact of COVID-19 nonpharmaceutical interventions on the future dynamics of endemic infections