Study design
This study was part of a cross-sectional, nationwide, multipurpose, mail survey of Japanese PwMSA from October to December, 2020. The data reflect the effects of the early COVID-19 pandemic, corresponding to 8 to 9months after the global pandemic was declared. Prior to this study, we reported another study of aspects of social services in Japan23, and all 155 participants in the present study were also included in that analysis.
The study received approval from the ethics committee of the Faculty of Health Science of Juntendo University (Approval Number 20-012) and was performed in accordance with the Declaration of Helsinki. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and the American Association for Public Opinion Research (AAPOR) reporting guideline.
The survey was anonymous, and confidentiality of information was assured. Informed consent was obtained from all participants by providing a written explanation of the study and having them return the questionnaire form. Because it was anticipated that certain patients did not want their responses to be included in the study, their return of a letter of intent to refuse to respond was also accepted.
The participants of this study were respondents to a survey of all members of the Japanese spinocerebellar degeneration and MSA patient association (https://scdmsa.tokyo/). This is the largest nonprofit organization patient group in Japan and is composed of volunteers. However, the members may not be the patients themselves, because they may be individuals who agree with the purpose of the association. MSA was self-reported by the patients in this study, but the diagnosis of MSA in Japan is made by specialists according to the common diagnostic criteria specified by the Ministry of Health, Labour and Welfare for registration of designated intractable diseases. The criteria are based on the second consensus statement on the diagnosis of MSA12. It was unlikely that an individual belonging to a patient association of rare diseases would self-report without it being based the correct diagnosis. The exclusion criteria for this study were those who were not PwMSA, and those who refused to respond or had incomplete answers to all the questions related to COVID-19.
Questionnaires were mailed to all members using the address database used to send regular patient association mailings. The relevant questions consisted of original COVID-19-related items and background information items that did not reflect COVID-19. The primary outcome was the effect of the COVID-19 pandemic on ICF functioning. The domains of ICF functioning consisted of body function, activity, and participation, and these definitions were in accordance with the WHO22. The self-perception of ICF functioning during the pandemic was assessed through the patients global impression at the time of response. Participants were asked to rate the impact score on each ICF functioning associated with COVID-19 on a 7-point scale: strongly unaffected=3, moderately unaffected=2, slightly unaffected=1, undecided=0, slightly affected=+1, moderately affected=+2, and strongly affected=+3. Of these, responses 1 to3 were classified as Unaffected, and responses of +1 to+3 score were classified as Affected, with the latter responses defined as COVID-19-related decline of ICF functioning. Thus, if domains of ICF functioning (body function, activity, and participation) were affected, the terms impairment, activity limitation, and participation restriction were used, respectively. The infection status and behavioral effects of COVID-19 were also included in the survey.
Participant were asked about age, sex, disease type, disease duration, and dwelling place (home, long-term care facility, hospitalization), and the multiple system impairment questionnaire (MSIQ), patient health questionnaire-2 (PHQ-2), modified rankin scale (mRS) score, barthel index (BI), life-space assessment (LSA), and EuroQoL (EQ) were examined. Of these, the clinical assessment indices were based on self-reported responses of normal conditions before the COVID-19 pandemic. The MSIQ for comprehensive scoring of the severity of disease-related impairments and the PHQ-2 as a screening tool for depression reflect body function as a baseline. The mRS score was used as a simple indicator of independence level, and the BI was used for comprehensive scoring of basic activities of daily living (ADL) assessment, reflecting activity as a baseline. The LSA was used for comprehensive scoring of the extent of daily living space, and the EQ was used as a global assessment of health-related QOL, and they reflected participation as a baseline.
The MSIQ was developed specifically for this study and was scored on a self-report basis for 22 impairments that may occur in MSA (Online Resource 1). All impairments were described in writing to ensure specific understanding. It consists of a total of 22 items: ataxia, muscle weakness/atrophy, muscle rigidity, spasticity, balance disorder, postural abnormality, decreased endurance, fatigue, pain, numbness, sensory disturbance, tremor, involuntary movements, orthostatic hypotension, poor sleep, respiratory disturbance, speech/dysarthria, dysphagia, visual impairment, urinary impairment, voiding impairment, and cognitive impairment. Each impairment was scored as 0 (no impairment) to 3 (severe impairment). Thus, the maximum score of 66 is the most severe impairment, and a score of 0 is the complete absence of impairments.
The PHQ-2 for depression screening24 is a shortened version of the PHQ-925. It consists of two items with a score of 03 each, with 0 being normal and 6 being the most severe24. The PHQ-2 was used instead of the PHQ-9, which contains a motor-related item26.
The mRS was originally developed as an assessment grade for disability or dependence in the ADL of stroke patients. Today, it is widely used in patients with neurological diseases. The score was rated on a six-point scale from 0 (asymptomatic) to 5 (severe disability)27.
The BI evaluates the performance of basic ADL, such as feeding, personal hygiene, bathing, and dressing on a scale of 0100. A higher number reflects a greater ability to function independently and has the advantage of being applicable to self-assessment and direct administration28. To allow for self-assessment by mail, the content of previous studies was used29.
The LSA is a self-report measure to summarize the distance (five distance levels ranging from room to out of town) and frequency (five frequency levels ranging from not at all to every day) an individual travels in a given period of time. The results are calculated by the LSA score, which is 120 for the most active30.
The EQ is a comprehensive measure of health-related QOL that is used worldwide31. In this study, the official Japanese version of the EQ five-dimension five-level questionnaire (EQ-5D-5L) was used, and an index value was calculated, with 1 the highest and 0 the lowest32.
In summary, to clarify the effect of the COVID-19 pandemic on MSA, ICF functioning during the pandemic was defined as the main outcome, potential predictors of functioning decline were defined as MSIQ, PHQ-2, mRS, BI, LSA, and EQ, and the potential confounders were age, sex, disease duration, and dwelling place.
Descriptive statistics are presented for demographic variables and functional outcomes during the COVID-19 pandemic for PwMSA. Continuous variables are presented as means (standard deviation) and categorical variables as numbers (%). Spearmans product rate correlation coefficients were calculated for the associations between ICF functioning scores related to the COVID-19 pandemic. To compare the affected patients with the unaffected patients on ICF functioning, group comparisons were performed using Students t-test for numerical variables, the MannWhitney U test for ordinal variables, and the 2 test when appropriate for categorical variables. A score of 0 was excluded from the analysis in that domain. Among the data of selected patients, missing values were excluded only for that item.
Univariate logistic regression analyses were performed on the identified variables to assess the potential risk factors for affected functioning domains during the COVID-19 pandemic. The dependent variable was a dummy variable that was set to 0 for unaffected (3 to1) and 1 for affected (+1 to+3) for each functioning domain, and the independent variables were the MSIQ, PHQ-2, mRS, BI, LSA, and EQ. Similar analyses were performed for each domain of ICF functioning (impairment, activity limitation, and participation restriction). The associations between risk factors and outcomes are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Finally, multivariate logistic regression analyses were performed to identify independent risk factors for affected function scores during the COVID-19 pandemic for each domain of ICF functioning. Age, sex, disease duration, and dwelling place were forced into the model as adjustment factors, and a stepwise variable increase method (likelihood ratio) was used with independent variables identified on univariate logistic regression analysis. ORs and 95% CIs are presented after adjustment for confounders, including age, sex, disease duration, and dwelling place. For multivariate analysis only, participants with even one missing value were excluded from the analysis, and only complete data were analyzed.
Data analysis was performed using SPSS statistical software version 27.0 (IBM Corp). The significance level was set at =0.05, and all tests were 2-tailed.
All procedures performed in the study were approved by the ethics committee of the Faculty of Health Science of Juntendo University (approval number 20-012).
Informed consent was obtained from all participants by providing a written explanation of the study and by their return of the questionnaire form.
CLEVELAND, Ohio X-rays find antiviral compounds in common foods, a diabetes drug may help prevent serious COVID-19 symptoms, and researchers uncover how much virus infected people spread.
Cleveland.com brings you the latest COVID-19 news and research for Friday Aug. 19, 2022.
Antiviral compounds found in common foods
Three natural compounds present in foods like green tea, olive oil and red wine are promising new candidates for the development of drugs to fight against the coronavirus, according to research published last week in the journal Communications Biology.
A group of researchers in Germany used high intensity x-rays created at the particle accelerator laboratory PETRA III in Hamburg to determine the precise molecular structure of an enzyme required for the replication of the coronavirus, and screen a library of compounds that bind to it and may prevent it from working.
To do this, they mixed the viral enzyme with over 500 different natural compounds and formed tiny crystals. They then illuminated the crystals with the bright light from the x-rays and used the pattern of light bouncing off the crystal structure to create an image of the enzyme accurate down to the level of individual atoms.
The screening showed that three chemical compounds called phenols bind to the enzyme: hydroxyethylphenol (YRL), isolated for the experiments from the henna tree Lawsonia alba, is a compound present in many foods such as red wine and virgin olive oil and used as an anti-arrhythmia agent. Hydroxybenzaldehyde (HBA) is a known anti-tumor agent and accelerates wound healing. It was isolated from the copperleaf Acalypha torta. Methyldihydroxybenzoate (HE9), isolated from the French marigold Tagetes patula, is an anti-oxidant with anti-inflammatory effect and is found in green tea.
All three compounds are already used as active substances in existing drugs, said Christian Betzel from the University of Hamburg The advantage of these substances is their proven safety, says Betzel,. These compounds naturally occur in many foods. However, drinking green tea will not cure your corona infection. Like it will not heal your wounds or cure your cancer. If and how a corona drug can be developed from these phenols is subject to further studies.
Diabetes drug Metformin may treat COVID-19
Researchers have found that metformin, a commonly prescribed diabetes medication, lowers the odds of emergency department visits, hospitalizations, or death due to COVID-19 by over 40%; and over 50% if prescribed early in onset of symptoms, said a study published Thursday in the New England Journal of Medicine. The study also found no positive effect from treatment with either ivermectin or low-dose fluvoxamine.
1,323 participants, some of whom were vaccinated and some who were not, were randomly assigned to receive one of the three drugs individually, a placebo, or a combination of metformin and fluvoxamine or metformin and ivermectin. During 3 to 14 days of treatment, each volunteer tracked their symptoms, and after 14 days, they completed a survey.
We are pleased to contribute to the body of knowledge around COVID-19 therapies in general, with treatments that are widely available, said Carolyn Bramante, MD, principal investigator of the study and an assistant professor of internal medicine and pediatrics at the University of Minnesota Medical School. Our trial suggests that metformin may reduce the likelihood of needing to go to the emergency room or be hospitalized for COVID-19.
How much virus does a person with COVID-19 exhale?
If youve tested positive for COVID, just how much are you spreading virus to others every time you cough, sneeze or just breathe out? One group of researchers at the University of Maryland School of Public Health aimed to find out. What they discovered was that people infected with the highly transmissible Alpha, Delta and Omicron variants of SARS-CoV-2 expel higher amounts of virus than do those infected with other variants, and some individuals spread significantly more virus than others.
They also found that vaccination does not prevent individuals from spreading the virus either. According to their research, individuals who contract COVID-19 after vaccination, even after a booster dose, still shed virus into the air.
Their preliminary findings, though not yet peer-reviewed, have been published on the site MedRxiv.
For the study, 93 people who were infected with SARS-CoV-2 between mid-2020 and early 2022 faced into a cone-shaped apparatus and sang, shouted, coughed and sneezed for 30 minutes, while an attached machine collected the particles they exhaled. The device, called a Gesundheit-II, separated out the fine aerosolized droplets measuring 5 micrometers or less in diameter, which can linger in the air and leak through cloth and surgical masks.
The participants infections were caused by strains including the Alpha variant, which emerged in late 2020, and the later Delta and Omicron variants. All participants with the latter two strains had been fully vaccinated before catching the virus.
The study authors write that their research underscores the importance on better indoor air quality, air filtration, and masking in minimizing viral transmission.
Kitsap County has committed roughly 90% of theCOVID-19 relief funding itreceived as part of the American Rescue PlanAct (ARPA) of 2021.
To date, Kitsap County has directed the spending of $47.6 millionout of $52.7 million it received from the federal government. The money will goto a varietyofprojects that relate to public health,homelessness, childcare, small business assistance, hospitality and tourism, and infrastructure like broadband expansion.
The spending is focusedon assisting communities disproportionately impacted by COVID-19, those who are homeless or at risk of it, those who are low-income, andsmall businesses,said Eric Baker, Kitsap County deputy county administrator.
Homelessness in Kitsap: South Kitsap's project for tiny home village gains traction again
An August report that details spending shows the amount of money invested in each category:$23.3millionforpublic health;$10 million for "lost revenue recovery";$9.9 million to address "negative economic impacts"; $8.9 million for infrastructure; and $650,000 for administration.
"Our money is largely being focused on going out into the public or addressing internal issues in the county that are affecting the public," Baker said.
Some projects that helphomelessnessinclude $3.4 million for the renovation ofthe former Olympic Fitness Club into a homeless shelter of over 75 bedson Mile Hill Drive and $272,000 for the Housing Solutions Center to create additional homelessness intervention teams.Another$250,000 will go to theDispute Resolution Center of Kitsap Countyto help rentersaddress potential eviction issueswithout involving the court system.
Some of themost expensive projects on the list: $7.2millionto improve the ventilation system for the Kitsap CountyJail and$6.6 million for Kitsap Public Utilities District'sbroadband node expansion project. In that project,up to 30 broadband nodes willbe built inunderserved areas to givepeoplegreater access to in-home reliable high-speed internet.
KPUD also secureda $470,512 budgetfor itsfree Wi-Fiexpansion project, in which24 Wi-Fihotspots will be constructed at Kitsap Transitparkand ride lots and other public facilities, according to county documents.
As for tourism and hospitality businesses,$60,000 has been dedicated toVisit Kitsap Peninsula for a project tocollaborate with the Port of Seattle andVisit Seattleand Olympic Peninsula to bring journalists and writers to the county to promote tourism, county documents said.
Kitsap Public Health Districtis slated to get $748,000 foritsnurse family partnership, which is anexpansion of in-home health assistance to expectant mothers and new families to improve birth outcomes, child development, kindergarten readiness and parenting practices.
YMCA of Pierce and Kitsap County's childcare programs are slated to get $519,000 forsubsidiesfor daytime and before- or after-school childcare for low-income families; $243,000will go to the organization'syouth andsenior programs.
Related: Kitsap tribes use COVID-19 relief funds to build housing, improve infrastructure
The county is working with stakeholdersto hammer out some contract-based projects andis making a goodprocessof spendingthe money, Baker said.
"We do have a number of contracts that have gone out. And then we have a number of projects that are internal, that are not necessarily contract-based, but we're making good progress towardspending the money," Baker said.
The spendingdeadline for the ARPA fund isthe end of2024.The countyis usingthe money in a way that ensures recovery needs beyond those identified in 2021can be covered, according to Baker.
"If we issued all our money last year,a lot of the stuff we know we need today, we wouldn't have money for it," Baker said. "The board is kind of moving methodicallywith this money, making sure that we're getting as much out there as we can, yet also ensuring that we have a certain amount to handle emergent issues that we didn't think of previously."
The countyplanstocommittherest of the $5 millionin 2023, Baker said.
This story has been changed since it was first published to correct the agency that runs the nurse family partnership.
Reach breaking news reporter Peiyu Lin at pei-yu.lin@kitsapsun.comor on Twitter@peiyulintw.
Support local journalism.Subscribe to kitsapsun.comtoday.
GAITHERSBURG, Md., Aug. 17, 2022 /PRNewswire/ -- Novavax, Inc. (Nasdaq: NVAX), a biotechnology company dedicated to developing and commercializing next-generation vaccines for serious infectious diseases, today announced that New Zealand's Medsafe has granted expanded provisional approval for Nuvaxovid (NVX-CoV2373) COVID-19 vaccine for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a heterologous and homologous booster dose in adults aged 18 and older.
Following the expanded provisional approval decision by Medsafe, New Zealand, people may now choose Nuvaxovid as their first and/or second COVID-19 booster dose(s) after completion of their primary series using any of the authorized COVID-19 vaccines.
"We are pleased to offer another booster choice and the only protein-based COVID-19 vaccine for those aged 18 and older in New Zealand," said Stanley C. Erck, President and Chief Executive Officer, Novavax. "As New Zealand endures winter months where thousands of COVID-19 infections are being recorded each day, we believe our vaccine is a strong option, particularly given its broad immune responses to a wide range of circulating variants."
The request for expanded provisional approval for the booster dose is supported by data from Novavax' Phase 2 trial conducted in Australia, from a separate Phase 2 trial conducted in South Africa, and from the UK-sponsored COV-BOOST trial. As part of the Novavax-sponsored Phase 2 trials, a single booster dose of Nuvaxovid was administered to healthy adult participants approximately six months after their primary two-dose vaccination series of Nuvaxovid. The third dose produced increased immune responses comparable to or exceeding levels associated with protection in Phase 3 clinical trials. In the COV-BOOST trial, Nuvaxovid induced a significant antibody response when used as a heterologous third booster dose.
In the Novavax-sponsored trials, following the booster, local and systemic reactions had a median duration of approximately two days. The incidence of Grade 3 or higher events remained relatively low. Safety reporting of reactogenicity events showed an increasing incidence across all three doses of Nuvaxovid, reflecting the increased immunogenicity seen with a third dose. Medically attended adverse events, potentially immune-mediated medical conditions, and severe adverse events occurred infrequently following the booster dose and were balanced between vaccine and placebo groups.
As a booster for adults, Nuvaxovid is also provisionally registered in Australia and approved in Japan, and is actively under review in other markets.
New Zealand previously granted provisional approvalfor Nuvaxovid in adults aged 18 and older in February 2022. Novavax' sponsor in Australia and New Zealand is Biocelect Pty. Ltd.
Trade Name in the U.S.The trade name Nuvaxovid has not yet been approved by the U.S. Food and Drug Administration.
Important Safety Information: New Zealand
For more information on Nuvaxovid, including the Summary of Product Characteristics with Package Leaflet, Prescribing Information and Important Safety Information, adverse event reporting instructions, or to request additional information, please visit the following websites:
About the Novavax COVID-19 vaccine (NVX-CoV2373)
The Novavax COVID-19 vaccine (NVX-CoV2373) is a protein-based vaccine engineered from the genetic sequence of the first strain of SARS-CoV-2, the virus that causes COVID-19 disease. The vaccine was created using Novavax' recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and is formulated with Novavax' patented saponin-based Matrix-M adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies. The Novavax COVID-19 vaccine contains purified protein antigen and can neither replicate, nor can it cause COVID-19.
The Novavax COVID-19 vaccine is packaged as a ready-to-use liquid formulation in a vial containing ten doses. The vaccination regimen calls for two 0.5 ml doses (5 mcg antigen and 50 mcg Matrix-M adjuvant) given intramuscularly 21 days apart. The vaccine is stored at 2- 8 Celsius, enabling the use of existing vaccine supply and cold chain channels. Use of the vaccine should be in accordance with official recommendations.
Novavax has established partnerships for the manufacture, commercialization, and distribution of its COVID-19 vaccine worldwide. Existing authorizations leverage Novavax' manufacturing partnership with Serum Institute of India, the world's largest vaccine manufacturer by volume. They will later be supplemented with data from additional manufacturing sites throughout Novavax' global supply chain.
About the Novavax COVID-19 vaccine (NVX-CoV2373) Phase 3 Trials
The Novavax COVID-19 vaccine (NVX-CoV2373) continues being evaluated in two pivotal Phase 3 trials.
PREVENT-19 (thePRE-fusion protein subunitVaccineEfficacyNovavaxTrial | COVID-19) is a 2:1 randomized, placebo-controlled, observer-blinded trial to evaluate the efficacy, safety and immunogenicity of the Novavax COVID-19 vaccine with Matrix-M adjuvant in 29,960 participants 18 years of age and over in 119 locations inthe U.S.andMexico. The primary endpoint for PREVENT-19 was the first occurrence of PCR-confirmed symptomatic (mild, moderate or severe) COVID-19 with onset at least seven days after the second dose in serologically negative (to SARS-CoV-2) adult participants at baseline. The statistical success criterion included a lower bound of 95% CI >30%. A secondary endpoint was the prevention of PCR-confirmed, symptomatic moderate or severe COVID-19. Both endpoints were assessed at least seven days after the second study vaccination in volunteers who had not been previously infected with SARS-CoV-2. In the trial, the Novavax COVID-19 vaccine achieved 90.4% efficacy overall. It was generally well-tolerated and elicited a robust antibody response after the second dose in both studies. Full results of the trial were published in theNew England Journal of Medicine(NEJM).
The pediatric expansion of PREVENT-19 is a 2:1 randomized, placebo-controlled, observer-blinded trial to evaluate the safety, effectiveness, and efficacy of the Novavax COVID-19 vaccine with Matrix-M adjuvant in 2,247 adolescent participants 12 to 17 years of age in 73 locations in the United States, compared with placebo. In the pediatric trial, the vaccine achieved its primary effectiveness endpoint (non-inferiority of the neutralizing antibody response compared to young adult participants 18 through 25 years of age from PREVENT-19) and demonstrated 80% efficacy overall at a time when the Delta variant of concern was the predominant circulating strain in the U.S.Additionally, immune responses were about two-to-three-fold higher in adolescents than in adults against all variants studied.
Additionally, a trial conducted in the U.K. with 14,039 participants aged 18 years and over was designed as a randomized, placebo-controlled, observer-blinded study and achieved overall efficacy of 89.7%. The primary endpoint was based on the first occurrence of PCR-confirmed symptomatic (mild, moderate or severe) COVID-19 with onset at least seven days after the second study vaccination in serologically negative (to SARS-CoV-2) adult participants at baseline. Full results of the trial were published inNEJM.
About Matrix-M Adjuvant
Novavax' patented saponin-based Matrix-M adjuvant has demonstrated a potent and well-tolerated effect by stimulating the entry of antigen-presenting cells into the injection site and enhancing antigen presentation in local lymph nodes, boosting immune response.
About Novavax
Novavax, Inc. (Nasdaq: NVAX) is a biotechnology company that promotes improved health globally through the discovery, development, and commercialization of innovative vaccines to prevent serious infectious diseases. The company's proprietary recombinant technology platform harnesses the power and speed of genetic engineering to efficiently produce highly immunogenic nanoparticles designed to address urgent global health needs. The Novavax COVID-19 vaccine, has received authorization from multiple regulatory authorities globally, including the FDA, European Commission, and the World Health Organization. The vaccine is currently under review by multiple regulatory agencies worldwide, including for additional indications and populations such as adolescents and as a booster. In addition to its COVID-19 vaccine, Novavax is also currently evaluating a COVID-seasonal influenza combination vaccine candidate in a Phase 1/2 clinical trial, which combines NVX-CoV2373 and NanoFlu*, its quadrivalent influenza investigational vaccine candidate, and is also evaluating an Omicron strain-based vaccine (NVX-CoV2515) as well as a bivalent format Omicron-based / original strain-based vaccine. These vaccine candidates incorporate Novavax' proprietary saponin-based Matrix-M adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies.
For more information, visitwww.novavax.comand connect with us on LinkedIn.
*NanoFlu identifies a recombinant hemagglutinin (HA) protein nanoparticle influenza vaccine candidate produced by Novavax. This investigational candidate was evaluated during a controlled phase 3 trial conducted during the 2019-2020 influenza season.
Forward-Looking Statements
Statements herein relating to the future of Novavax, its operating plans and prospects, its partnerships, the timing of clinical trial results, the ongoing development of NVX-CoV2373, including an Omicron strain based vaccine and bivalent Omicron-based / original strain based vaccine, a COVID-seasonal influenza investigational combination vaccine candidate, the scope, timing and outcome of future regulatory filings and actions, including Novavax' plans to supplement existing authorizations with data from the additional manufacturing sites in Novavax' global supply chain, additional worldwide authorizations of NVX-CoV2373 for use in adults and adolescents, and as a booster, the evolving COVID-19 pandemic, the potential impact and reach of Novavax and NVX-CoV2373 in addressing vaccine access, controlling the pandemic and protecting populations, the efficacy, safety and intended utilization of NVX-CoV2373, and the expected administration of NVX-CoV2373 are forward-looking statements. Novavax cautions that these forward-looking statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include, without limitation, challenges satisfying, alone or together with partners, various safety, efficacy, and product characterization requirements, including those related to process qualification and assay validation, necessary to satisfy applicable regulatory authorities; difficulty obtaining scarce raw materials and supplies; resource constraints, including human capital and manufacturing capacity, on the ability of Novavax to pursue planned regulatory pathways; unanticipated challenges or delays in conducting clinical trials; challenges meeting contractual requirements under agreements with multiple commercial, governmental, and other entities; and those other risk factors identified in the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Novavax' Annual Report on Form 10-K for the year ended December 31, 2021 and subsequent Quarterly Reports on Form 10-Q, as filed with the Securities and Exchange Commission (SEC). We caution investors not to place considerable reliance on forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at www.sec.govand www.novavax.com, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this document, and we undertake no obligation to update or revise any of the statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.
Contacts:
InvestorsErika Schultz | 240-268-2022[emailprotected]
MediaAli Chartan or Giovanna Chandler | 202-709-5563[emailprotected]
SOURCE Novavax, Inc.
CLAIM
New paper suggests Covid mRNA vaccination rates are linked to increases in overall deaths
DETAILS
Misrepresents source: The preprint used to support the claim investigated the correlation between the distribution of mortality across Dutch cities and COVID-19 vaccination coverage. However, Berenson presented some numerical results as if it were an increase in overall mortality. Furthermore, this numerical result wasnt adjusted for possible bias. Inadequate support: The preprint used to support the claim used city-level data and not individual-level data which precludes drawing conclusions on the impact of vaccination on the risk of dying. Furthermore, all possible confounding factors arent accounted for, which may bias the final results.
KEY TAKE AWAY
COVID-19 vaccines have been tested in several large clinical trials. Their effectiveness largely outweigh the risk of rare side effects. A study comparing vaccination coverage and all-cause mortality in Dutch cities doesnt show that COVID-19 vaccines increase the risk of dying. The studys design is not appropriate to draw such a conclusion.
REVIEW More than 80% of the Dutch population over 12 has been vaccinated against COVID-19, as of August 2022. Large clinical trials and ongoing monitoring of the millions vaccinated worldwide show that COVID-19 vaccines effectiveness largely outweigh the risks of rare side effects and effectively protect against severe forms of the disease.
However, inaccurate claims that these vaccines are dangerous, increase the risk of death, or weaken the immune system frequently circulated on social media, and Health Feedback already debunked several of them.
Journalist Alex Berenson made such a claim in July 2022 when he stated on Substack that new results suggested Covid mRNA vaccination rates are linked to increases in overall deaths. Berenson had made multiple inaccurate and misleading claims about COVID-19 and vaccines that Health Feedback previously debunked.
In his article from 28 July 2022, Berenson reported on a preprint (a study not yet peer-reviewed or accepted by a journal) published by Andr Redert, who previously worked as a researcher in computing sciences but is not trained in virology, immunology, or epidemiology. In that preprint, Redert compared the all-cause mortality and vaccination coverage in Dutch cities.
Although Berenson acknowledged that the preprint doesnt demonstrate that vaccination caused an increase in all-cause mortality, this is implied by the Substack articles headline. Berenson also combined his take on Rederts preprint with observations of increased all-cause mortality in highly vaccinated countries. Regardless of whether this last statement is accurate, it is clear that Berensons subtext is that mRNA vaccination causes an increase in mortality. The readers comments section at the bottom of the article clearly shows that this is how his article is interpreted.
As we explain below, however, Berensons interpretation is incorrect and based on a flawed interpretation of the preprints results. Rederts preprint itself suffers from limitations that weaken the conclusions that can be made about vaccine safety.
In his paper, Redert looked at the distribution of mortality and vaccination coverage between Dutch cities. Some cities presented an all-cause mortality above average, and others, below. Similarly, some cities had vaccination coverage above the national average and other cities below. Redert then tried to determine if there was a correlation between the two and, if so, what proportion of the mortality was distributed across cities in the same way as vaccination coverage. In other words, Redert asked to what extent a city with an above average vaccination coverage would see its all-cause mortality also rise above average or, conversely, drop below average.
Redert observed that the weekly mortality partially correlated with vaccine coverage. In other words, cities with an all-cause mortality above average tended to also exhibit vaccination coverage above average.
However, it is important to stress that Rederts preprint only established correlations between vaccination coverage and mortality, and didnt demonstrate any causal association. Correlation by itself doesnt prove that one event is the cause of another. Rederts preprint also doesnt provide any biological explanation or medical evidence showing that vaccination increases the likelihood of dying.
Furthermore, Redert used city-level data: all-cause mortality and vaccination coverage in that same city. Drawing conclusions on the risk of individuals dying from average data obtained at the city level is known as an ecological fallacy. In our case, city-level data tell us nothing as to whether vaccinated people were overrepresented among those who died, for instance.
Therefore, data from Rederts preprint arent suitable to support Berensons suggestion that vaccination is linked to an increase in all-cause mortality.
In his account of Rederts preprint, Berenson misinterpreted some of the results and used them to draw ill-founded conclusions.
Redert provided the example of a given week where 5% of the total 4,000 deaths from all causes of that weekthat is, 200 deathswere distributed between cities in the same way the vaccination coverage was. The remaining 3,800 deaths were distributed across cities in a manner uncorrelated with vaccination coverage.
Berenson apparently interpreted this 5% of vaccination-correlated mortality as an increase in the total number of deaths, because he also claimed that his 5% figure was consistent with other data reporting a 5% excess mortality in several countries. He then went on to comment that a 5% increase would actually represent many more dead people in the long run.
However, Berensons interpretation of this piece of data is erroneous. This 5% figure from Rederts preprint is not related to the number of all-cause deaths that Berenson cited. Rederts analysis focused on the distribution of deaths across all cities, not on the total number of deaths. In fact, Redert warned: These [5% deaths] are not 200 additional deaths related to vaccination, it means that 200 out of 4k deaths were distributed over municipalities in the same pattern as vaccination coverage.
Also, this 5% figure is the result of Rederts analysis for one weekweek 50 of 2021used as an example and isnt necessarily representative of the entire pandemic, contrary to what Berenson suggested.
Third, many confounding factors bias the direct comparison of all-cause mortality and vaccination coverage. Confounding factors are variables that affect the outcome of an experiment, but arent the variables being studied. If scientists dont factor in the influence of confounding factors in their study, they may draw erroneous conclusions about causality. For example, older people are more likely to get vaccinated against COVID-19 and to die from any cause. Therefore, one would expect that cities with an older population will exhibit a higher than average vaccination coverage and a higher all-cause mortality without any causal association between the two.
Redert was well aware of these confounding factors and proposed a way to take them into account by normalizing his results to pre-pandemic mortality data. However, this 5% figure Berenson extracted from the preprint comes from the raw data and not from the normalized data adjusted for confounding factors. Considering all the above, it is clear that Berensons take on Rederts paper is thus flawed and his conclusions are inaccurate.
Even when considering the adjustments for confounding factors proposed by Redert, the studys design limits what can be concluded from it.
First, Redert used weekly mortality data, but these data were compared with the final vaccination coverage of November 2021. In order to really compare if the mortality correlated with the vaccination coverage, at least partially, it would be better to use mortality and vaccination coverage data from the same week. Given that the study aimed to investigate whether vaccination impacted all-cause mortality, one could even imagine comparing the mortality of a given week with the vaccination coverage of an earlier time period, but not with the final vaccine coverage.
Second, Redert took into account some important confounding factors by normalizing his results by the mortality in 2019, before the COVID-19 pandemic. While this can correct confounding factors due to demographic, such as age or wealth, it would not correct for any other possible confounding factors that would affect both all-cause mortality and vaccine coverage during the pandemic. For instance, we can hypothesize that cities heavily impacted by COVID-19 will tend to vaccinate more, resulting in higher vaccination coverage, but at the same time would suffer from greater disruption to vital elements such as transport and healthcare that could worsen all-cause mortality.
Berenson incorrectly suggests that COVID-19 vaccination can increase all-cause mortality based on the results from a non-peer-reviewed publication. However, Berensons interpretation of the publication is flawed. Furthermore, several limitations in the design of the study itself make it impossible to draw conclusions from the results. By contrast, large clinical trials, as well as the millions vaccinated against COVID-19 in real-world conditions show that COVID-19 vaccines benefits largely outweigh their risks.
Challenges And Opportunities As mRNA Manufacturing Spreads Its Wings Beyond COVID-19 Vaccines In Vivo
A recent article published inCell Reports Medicine demonstrated that Bacillus Calmette-Guerin (BCG) vaccinations might offer a platform for protection against emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and other pathogenic infections in type 1 diabetics.
During the past 17 years, randomized clinical studies and epidemiological investigations showed that the BCG vaccine against tuberculosis protected people from numerous infections, such as upper respiratory tract infections, malaria, leprosy, bacterial, and viral infections. Additionally, the BCG vaccine might safeguard humans from immunological disorders like multiple sclerosis and type 1 diabetes.
There is a demand for effective and safe platform vaccines to immunize against SARS-CoV-2 infection and other contagious pathogens. As the SARS-CoV-2 pandemic got underway, epidemiological studies started to find a link between neonatal BCG vaccination and lower coronavirus disease 2019 (COVID-19) mortality and morbidity, even in elderly adults decades following the standard newborn vaccinations on a nation-by-nation basis. On the contrary, several global groups with various neonatal exposures, BCG strains, and other communities did not exhibit these benefits.
Since adults or newborns have never received the BCG vaccine in the United States (US), a randomized study of BCG for potential COVID-19 protection provides a clear comparison in a vaccine-naive US adult population.
In the current placebo-controlled, double-blinded, randomized phase II/III research, the scientists assessed the efficacy and safety of the multi-dose BCG vaccinations for preventing COVID-19 and other infectious illnesses in a SARS-CoV-2-unvaccinated, high-risk-community-based group, over 15 months, from 1 January 2020 to April 2021.
The authors aimed to discover whether the BCG vaccine would provide a platform vaccine approach to safeguard against a wide range of infectious diseases, such as SARS-CoV-2 infection in the at-risk population.
Type 1 diabetic adults were considered the high-risk group in the study. The team recruited 144 participants and randomly assigned 48 to placebo and 96 to BCG arms. Further, no volunteers dropped out during the 15-month research.
The present parallel trial was derived from an ongoing randomized, double-blinded study of BCG for treating long-established adult type 1 diabetes. Therefore, all participants were fully immunized with three BCG or placebo vaccinations at the SARS-CoV-2 pandemic onset in the US on 1 January 2020.
The study results indicated that, contrary toantigen-specific COVID-19 vaccinations, no participants experienced any systemic side effects from BCG during the vaccination period. Localized skin reactions are a known side effect of the BCG vaccine and typically start between two and four weeks after vaccination. No excessive local responses were documented as adverse reactions. Notably, other SARS-CoV-2 vaccinations were not yet available during the timespan of the trial and had no impact on the research.
The BCG vaccine was 92% effective against SARS-CoV-2 infection, with a cumulative incidence of 1% of BCG-treated subjects and 12.5% of placebo-treated volunteers meeting the criteria for confirmed COVID-19 diagnosis based on symptoms and positive serologies. Besides, the team discovered no polymerase chain reaction (PCR)-positive symptomatic subjects in the BCG arm, i.e., 0%, compared to five symptomatic, PCR-positive participants in the placebo cohort, i.e., 10.4%.
If only the PCR data were regarded, these results demonstrated 100% efficacy for the BCG vaccine against SARS-CoV-2 infection at 0.99 posterior probability. In addition, there were no SARS-CoV-2-related deaths in either the placebo group or the BCG group.
The researchers noted that excluding the COVID-19 viral epitope II, practically all SARS-CoV-2 domains included in the heatmap comparisons exhibited anoticeably greater cumulation of antibody reactivity in the placebo cohort relative to the BCG arm. Besides, BCG vaccination decreased the duration and severity of all infectious illness symptoms versus the placebo group.
Moreover, the study data showed that all infectious illness symptoms of BCG recipients were similar to or less severe than those of their household members. On the other hand, relative to their household members, most placebo participants experienced a more severe illness. BCG recipients typically felt mildersymptoms than placebo recipients or non-diabetic householdcontrols.
In conclusion, the study illustrated that the BCG vaccine offers efficient protection against COVID-19 and comprehensive protection against other infectious diseases in type 1 diabetic adults in the US.
The study findings also depicted that the BCG vaccination was efficient, safe, cost-effective, and perhaps protective against the constantly evolving SARS-CoV-2 strain of the COVID-19 pandemic, given its extensive protection against other infections. The authors mentioned that although the efficacy of the BCG vaccine requires one to two years to manifest, the immunity might last decades.
Effectiveness of BNT162b2 Vaccine against Omicron in Children 5 to 11 Years of Age | NEJM nejm.org
