Hospital-acquired (nosocomial) COVID-19 transmission was associated with higher rates of 30-day mortality and more severe disease during the early phases of the pandemic, but the risk has lessened in the post-Omicron landscape, according to a new study from JAMA Network Open based on outcomes seen in Sweden during the past 3 years.
Outcomes of nosocomial SARS-CoV-2 infections are important metrics for hospital prevention and control measures, including masking, ventilation, and mandatory testing of patients. The authors of the study said up-to-date assessments of hospital-acquired COVID-19 infections is needed for the planning and implementation of infection prevention and control (IPC) measures.
In an editorial on the study, clinicians from Harvard University and Brigham and Women's Hospital in Boston said, "Hospital leaders face the dilemma of deciding whether hospitals and clinics can also revert to prepandemic practices or whether health care ought to be different."
The study looked at the incidence rate of nosocomial SARS-CoV-2 infections across all hospitals in Stockholm, Sweden, from March 1, 2020, to September 15, 2022, and the associated 30-day mortality rates, matching cases with nonCOVID-19 hospitalized patients and outcomes.
The proportion of community-acquired, indeterminate, and nosocomial SARS-CoV-2 infections along with the incidence rate of nosocomial SARS-CoV-2 was estimated using data on all SARS-CoV-2 infections, the authors said.
A total of 438,640 SARS-CoV-2 infections were identified during the study period, of which 2,203 nosocomial SARS-CoV-2 infections among 2,193 patients were identified (a few patients were infected more than once). The overall incidence rate of nosocomial SARS-CoV-2 was 1.57 (95% confidence interval [CI], 1.51 to 1.64) per 1,000 patient-days.
The median age for nosocomial patients was 80 years, and 50.5% were women.
The 30-day mortality rate dropped significantly across the study period, from 34% for nosocomial admitted cases in the prevaccination period (95% CI, 31% to 38%) to 10% (95% CI, 8% to 12%), in the post-Omicron phase.
The excess 30-day mortality was almost 3 times higher in the COVID-19 group compared with the nonCOVID-19 group in the prevaccination period, resulting in a roughly 20% absolute increased risk of death in patients who acquired nosocomial COVID-19, the authors said.
"During the Omicron variant wave, after an extensive vaccination campaign, nosocomial infections were not independently associated with excess mortality, suggesting that the role of IPC [infection prevention and control] measures may help prevent excess deaths with successful vaccination and/or less severe virus variants," the authors concluded.
Nosocomial infections were not independently associated with excess mortality.
In the editorial, the authors write that the study findings suggest nosocomial transmission and mortality after the Omicron period seems to be no longer statistically significant.
"It is very difficult to imagine hospitals reverting to the full array of infection prevention measures they put in place at the height of the pandemic," they write. "We have reached a point at which we can be selective about both the measures we choose and when we implement them. Masking, admission testing, and visitor screening are likely the highest yield interventions."
GAITHERSBURG, Md., Nov. 17, 2023 /PRNewswire/ -- Novavax, Inc. (Nasdaq: NVAX), a global company advancing protein-based vaccines with its Matrix-M adjuvant, today announced changes to its executive leadership team designed to enhance focus on its strategic priorities and continue the evolution of the Company's scale and structure announced last week.
John Trizzino will take on the newly created role of President and Chief Operating Officer for the Company. In this role, Mr. Trizzino will lead the commercial; chemistry, manufacturing and controls or CMC; and regulatory functions. He will continue to serve on the Company's executive leadership team.
Current Chief Legal Officer and Corporate Secretary John Herrmann will retire effective December 8, and Mark Casey will join the Company as his successor effective December 11. Mr. Casey will also serve on the Company's executive leadership team.
"As we announced last week, we are keenly focused on effectively delivering our COVID-19 product to market and evolving Novavax's scale and structure to position the Company for future success. In his new role as Chief Operating Officer, John Trizzino will focus on all aspects of successful product delivery, both for the 2023-2024 vaccination season and beyond. His deep knowledge of the Company and our processes will help to facilitate the transition to a more streamlined and efficient operating model," said John C. Jacobs, President and Chief Executive Officer, Novavax. "As Chief Legal Officer for nearly 14 years, John Herrmann helped transition Novavax from a clinical development organization to a global commercial vaccine company during a worldwide pandemic. We are incredibly grateful for his leadership, and I am delighted that John has agreed to serve as an advisor to me and the Company for the next year. His successor, Mark Casey, brings more than 30 years of experience to Novavax, and we look forward to the next chapter with him at the helm of our legal team."
Mr. Trizzino has broad experience in publicly held companies and over 25 years in the vaccines market. During his 12 years with Novavax, Mr. Trizzino most recently served as Executive Vice President, Chief Commercial Officer and Chief Business Officer, and has also held the roles of Chief Financial Officer, Senior Vice President of Commercial Operations and Senior Vice President of Business Development. Previously, Mr. Trizzino served as Chief Executive Officer of Immunovaccine, successfully leading the company into clinical development within the infectious disease and cancer immunotherapy business, and has also held leadership roles at MedImmune, LLC (now AstraZeneca), ID Biomedical and Henry Schein, Inc. Mr. Trizzino holds a Bachelor of Science from Long Island University and a Master of Business Administration from New York University, Stern School of Business.
Mr. Casey has decades of experience in the life sciences sector and most recently served as Chief Legal Officer and Corporate Secretary at Bryn Pharma. He previously served as Chief Legal Officer, Corporate Secretary and Executive Chairman of the Board - Specialty Generics at Mallinckrodt Pharmaceuticals where he led business turnaround inclusive of enhancing profitability through rationalization of the R&D portfolio, identifying applications for underutilized manufacturing capacity and executive-level changes. Earlier in his career, Mr. Casey held executive leadership roles at Idera Pharmaceuticals and Hologic and held roles of increasing responsibility at Boston Scientific and EMC Corp. Mr. Casey holds a Bachelor of Science from Syracuse University and a Juris Doctor from Suffolk University Law School.
About Novavax Novavax, Inc. (Nasdaq: NVAX) promotes improved health by discovering, developing and commercializing innovative vaccines to help protect against serious infectious diseases. Novavax, a global company based in Gaithersburg, Md., U.S., offers a differentiated vaccine platform that combines a recombinant protein approach, innovative nanoparticle technology and Novavax's patented Matrix-M adjuvant to enhance the immune response. Focused on the world's most urgent health challenges, Novavax is currently evaluating vaccines for COVID-19, influenza and COVID-19 and influenza combined. Please visit novavax.com and LinkedIn for more information.
Forward-Looking Statements Statements herein relating to the future of Novavax, its operating plans and prospects, including the continued evolution of the Company's scale and structure, and the effective delivery of its updated XBB version of its Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula) (NVX-CoV2601) 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; challenges or delays in obtaining regulatory authorization for its product candidates, including its updated XBB version of its COVID-19 vaccine in time for the fall 2023 vaccination season or for future COVID-19 variant strain changes; challenges or delays in clinical trials; manufacturing, distribution or export delays or challenges; Novavax's exclusive dependence on Serum Institute of India Pvt. Ltd. for co-formulation and filling and the impact of any delays or disruptions in their operations on the delivery of customer orders; challenges in obtaining commercial adoption of our updated protein-based non-mRNA XBB COVID-19 vaccine, NVX-CoV2373 or any COVID-19 variant strain-containing formulation; 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's Annual Report on Form 10-K for the year ended December 31, 2022 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.gov and 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: Investors Erika Schultz 240-268-2022 [emailprotected]
Media Ali Chartan 240-720-7804 media@novavax.com
SOURCE NOVAVAX, INC
For more than 100 years, American women have outlived American men, largely due to differences in rates of cardiovascular disease and lung cancer. Now COVID-19 has widened the gendered life expectancy gap, according to a research letter published yesterday in JAMA Internal Medicine.
The study was based on mortality data from the National Center for Health Statistics, and it compared life expectancy at birth between men and women from 2010 to 2021, divided by pre and postCOVID-19 year, and cause-specific mortality.
It's already been well-documented that the COVID-19 pandemic lowered life expectancy rates for all US adults, with expectancy at birth decreasing from 78.8 years in 2019 to 76.1 years in 2021.
In 2010, US women were expected to live 4.8 years longer than male counterparts, but by 2021 that gap increased to 5.8 years. From 2010 to 2019, the gender life expectancy gap increase by only 0.23 years. From 2019 and 2021 it increased by 0.70 years.
"From 2019 to 2021, COVID-19 became the leading contributor to the widening gender life expectancy gap (0.33 years [39.8%]) followed by unintentional injuries (0.27 years [32.5%]," the authors wrote. From 2010 to 2019, the gender mortality gap was caused by unintentional injuries, diabetes, suicide, homicide, and heart disease.
The absolute difference in age-adjusted death rates between men and women increased from 252 to 315 per 100,000 from 2010 to 2021, the authors found.
Men experiences higher mortality rate from COVID-19 for many reasons, mostly because they carry a higher burden of comorbidities that make them susceptible to severe COVID, the authors note. Men also experience more socioeconomic factors, including incarceration and homelessness, that have been linked to COVID-19 deaths.
We need to track these trends closely as the pandemic recedes.
"Differentially worsening mortality from diabetes, heart disease, homicide, and suicide suggest that chronic metabolic disease and mental illness may also contribute," the authors said.
They also note that increasing deaths of despair among men spotlight the contributions that drug use and firearms make in the gendered age gap.
In a University of California - San Francisco press release,senior author Howard Koh, MD, MPH, of the Harvard T.H. Chan School of Public Health, said, "We need to track these trends closely as the pandemic recedes. And we must make significant investments in prevention and care to ensure that this widening disparity, among many others, do not become entrenched."
The School of Chinese Medicine at Hong Kong Baptist University (HKBU) found that 55% of the patients who sought medical treatment from the HKBU Chinese Medicine Telemedicine Centre Against COVID-19 during the fifth wave of the COVID-19 pandemic continued to experience at least one long COVID symptom for six months to a year after diagnosed with an infection. The most common symptoms are fatigue, brain fog and cough.
The study also revealed that patients who took Chinese medicine after COVID-19 infection took a shorter time to test negative in rapid tests, and experienced significant symptom relief compared to patients who did not take Chinese medicine.
The research findings have been published in a number of papers in international academic journals including the Journal of Medical Virology and The American Journal of Chinese Medicine.
HKBU established the HKBU Chinese Medicine Telemedicine Centre Against COVID-19 in 2021 during the fifth wave of the COVID-19 pandemic in Hong Kong to provide free telemedical services for COVID-19 patients. Making reference to the treatment protocols and clinical experiences in Mainland China, the expert team of HKBUs School of Chinese Medicine formulated the Chinese Medicine Clinical Guidelines for COVID-19 in Hong Kong as the Universitys clinical diagnosis and treatment standards for COVID-19. The Telemedicine Centre follows the guidelines to provide diagnosis, treatment, and prevention services to COVID-19 patients, close contacts, and caregivers.
Coughing is the most common early symptom of infection
The HKBU research team led by Professor Bian Zhaoxiang, Director of the Clinical Division at the School of Chinese Medicine, conducted a retrospective study using patient statistics collected by the Telemedicine Centre during the fifth wave of the pandemic. The team analysed the symptoms in the first four weeks of about 13,000 patients who were infected with COVID-19 from mid-March to early May in 2022 and underwent home isolation.
The results showed that 93% of patients experienced at least one symptom. The most common symptoms during the first week of infection were cough (91%), sputum (75%), dry throat (50%) and sore throat (44%). 17% of patients still had these symptoms four weeks after infection. Although the symptoms gradually subsided over time, the prevalence of fatigue increased.
Chinese medicine accelerates viral clearance
Among this batch of patients, the research team selected 311 patients who had taken Chinese medicine for five days within 10 days after diagnosis, and another 311 patients who had not taken any Chine medicine during the same period to evaluate the efficacy of Chinese medicine.
The results showed that patients who took Chinese medicine within 10 days after COVID-19 infection needed an average of seven days to test negative in rapid tests, and experienced an average of four symptoms, which were significantly milder compared to patients who didnt take Chinese medicine. The average time to test negative for patients who did not take Chinese medicine was eight days, and they experienced an average of 11 symptoms. The results show that Chinese medicine is an effective treatment for COVID-19 infection.
Over half of the patients experience long COVID after six months
The research team conducted a follow-up telephone survey from November 2022 to January 2023 with 6,242 COVID-19 patients who sought medical consultation at the Telemedicine Centre between December 2021 and May 2022 to understand their symptoms and risk factors after six months to a year of infection.
The study found that 55% of patients still experienced at least one long-term symptom, i.e. long COVID or post-COVID syndrome. The most common symptoms were fatigue (36%), brain fog (34%) and cough (31%). Furthermore, females, middle-aged persons, obese people, those with comorbidities such as ophthalmology or otorhinolaryngology diseases, digestive system diseases, respiratory diseases, hyperlipidemia and cardiovascular diseases, and patients with more initial symptoms were more likely to develop long COVID. However, there was no significant correlation between taking three or more doses of vaccine and the occurrence of long COVID.
Professor Bian said: HKBU established the Telemedicine Centre during the COVID-19 outbreak to provide free treatments for COVID-19 patients. We analysed the Centres data to deepen the medical communitys understanding of the symptoms during the early and middle stages of COVID-19 infection as well as the post-COVID syndrome. It allows the public to understand the effectiveness of Chinese medicine in treating COVID-19. The study also shows that the tele-services of Chinese medicine can be an important component of Hong Kongs healthcare and disease prevention system.
Compared to the 3 years prior to the pandemic, children with medically complex conditions and otherwise healthy children saw decreases in severe non-COVID respiratory illnesses in 2020 and 2021, the authors of a study yesterday note in JAMA Network Open.
The cross-sectional study, based on 139,078 respiratory hospitalizations in Canada, shows that the mitigation efforts used during the first several months of COVID-19 likely prevented serious outcomes from respiratory illness complications, including hospitalizations, intensive care unit (ICU) admissions, and death.
Previous studies have shown that the COVID-19 prevention strategies used by many countries were associated with substantial reductions in circulating levels of respiratory syncytial virus and influenza. This is one of the first studies, however, to examine severe respiratory illness occurrence among children with medical complexity (CMC) and without medical complexity (non-CMC).
CMC include those with neurologic impairment (NI), which accounts for 28% of all Canadian CMC, children with congenital heart diseases, cystic fibrosis, and sickle cell disease.
The study was based on hospitalizations tracked in the Canadian Institutes for Health Information Discharge Abstract Database (CIHI-DAD) from April 1, 2017, to February 28, 2022, for all children 18 years and under, excluding residents of Quebec.
A CMC hospitalization was defined as a child with any complex chronic condition or NI diagnosis code recorded in the 5 years before the index hospitalization, the authors said. The prepandemic period was April 1, 2017 through March 1, 2020, and the pandemic phase of the study was April 2020 through February 2022.
The researchers limited capture of data on COVID-19 diagnoses to children who had an additional respiratory illness, such as pneumonia. "Although we may have missed some cases that were misclassified, at the time, 43.2% of Canadian children admitted to hospital with SARS-CoV-2 infections were not admitted because of COVID-19 (they typically had incidental SARS-CoV-2 infection detected during universal screening at hospital admission)," they wrote.
In total there were 139,078 respiratory hospitalizations (29,461 for CMC and 109,617 for non-CMC) from March 1, 2017, to February 28, 2022, and children ages 2 and younger accounted for 34.8% of CMC hospitalizations and 51.7% of non-CMC hospitalizations.
During the first year of the pandemic, CMC annual respiratory hospitalization rates drops from 1,385.6 per 10,000 hospitalizations per year to 611.4 per 10,000 CMC, an annual rate difference of 774.2 per 10000 CMC and a rate ratio (RR) of 0.44 (95% confidence interval [CI], 0.42 to 0.46).
Among non-CMC, the drop was even greater, from 52.9 per 10,000 in the prepandemic years to 9.7 per 10,000 in 2020.
Respiratory ICU admissions for CMC decreased from 441.8 per 10,000 prepandemic to 248.9 per 10,000 (RR, 0.56 [95% CI, 0.53 to 0.59]) in 2020 and 292.7 per 10,000 (RR, 0.66 [95% CI, 0.63-0.70]) in 2021.
Among CMC, compared with prepandemic (33.8 per 10000), mortality during respiratory hospitalizations decreased in both 2020 (21.2 per 10000; RR, 0.63 [95% CI, 0.51 to 0.77]) and 2021 (24.2 per 10,000; RR, 0.72 [95% CI, 0.59 to 0.87])
Taken together, this degree of serious respiratory illness reduction over the 2 pandemic years corresponds to a decrease in over 44,500 hospitalizations among Canadian children.
"Taken together, this degree of serious respiratory illness reduction over the 2 pandemic years corresponds to a decrease in over 44,500 hospitalizations among Canadian children (7409 for CMC, 37448 for non-CMC)," the authors wrote.
In addition, the data reflected more than 4,200 fewer ICU admissions (1,829 for CMC, 2,460 for non-CMC) and a decrease of 119 CMC in-hospital deaths.
"The decline observed among CMC is clinically important and was associated with decreased mortality," the authors noted.
Key Points
Question What is the association between exposure to the COVID-19 pandemic and preschool-aged childrens cognitive and emotional development?
Findings In this cross-sectional study including data from the Ontario Birth Study, pandemic-exposed children had significantly higher problem solving and fine motor skills at 24 months of age but lower personal-social skills compared with nonexposed children. At 54 months of age, pandemic-exposed children had significantly higher vocabulary, visual memory, and overall cognitive performance compared with nonexposed children.
Meaning These findings suggest that health care practitioners and educators may encounter a mix of pandemic-related outcomes among young children as they plan recovery efforts following the pandemic.
Importance The association between COVID-19 social disruption and young childrens development is largely unknown.
Objective To examine associations of pandemic exposure with neurocognitive and socioemotional development at 24 and 54 months of age.
Design, Setting, and Participants This cross-sectional study evaluated associations between pandemic exposure vs nonexposure and developmental outcomes with covariate adjustment using data from the Ontario Birth Study collected between February 2018 and June 2022. Eligible participants were children aged 24 and 54 months. Data were analyzed from June to November 2022.
Exposure COVID-19 pandemic exposure defined as assessment after March 11, 2020.
Main Outcome and Measures Neurodevelopmental assessment using the ASQ-3 (Ages and Stages Questionnaire, Third Edition) and MCHAT-R (Modified Checklist for Autism in Toddlers, Revised) at 24 months of age, and neurocognitive and socioemotional assessment using the National Institutes of Health Toolbox at 54 months of age.
Results A total of 718 children at age 24 months (mean [SD] age, 25.6 [1.7] months; 342 female [47.6%]; 461 White [64.2%]) and 703 at age 54 months (mean [SD] age, 55.4 [2.6] months; 331 female [47.1%]; 487 White [69.3%]) were included. At 24 months of age, 460 participants (232 female [50.4%]) were assessed during the pandemic (March 17, 2020, to May 17, 2022) and 258 (110 female [42.6%]) were assessed prepandemic (April 17, 2018, to March 10, 2020). At 54 months of age, 286 participants (129 female [45.1%]) were assessed from March 14, 2020, to June 6, 2022, and 417 (202 female [48.4%]) were assessed from February 8, 2018, to March 10, 2020. At 24 months of age, pandemic-exposed children had reduced risk of problem-solving difficulties using cutoff scores (odds ratio [OR], 0.33; 95% CI, 0.18-0.62; P=.005) and higher problem-solving (B, 3.93; 95% CI, 2.48 to 5.38; P<.001) compared with nonexposed children. In contrast, pandemic-exposed children had greater risk for personal-social difficulties using cutoff scores (OR, 1.67; 95% CI, 1.09-2.56; P=.02) and continuous scores (B, 1.70; 95% CI, 3.21 to 0.20; P=.02) compared with nonexposed children. At 54 months of age, pandemic-exposed children had higher receptive vocabulary (B, 3.16; 95% CI, 0.13 to 6.19; P=.04), visual memory (B, 5.95; 95% CI, 1.11 to 10.79; P=.02), and overall cognitive performance (B, 3.89; 95% CI, 0.73 to 7.04; P=.02) compared with nonexposed children, with no differences in socioemotional development.
Conclusions and Relevance This cross-sectional study found both positive and negative associations between pandemic exposure and preschool childrens cognitive and emotional well-being within a relatively socioeconomically advantaged sample.
The COVID-19 pandemic produced pervasive social disruption, widely believed to have affected the well-being of children and families.1-3 In Toronto, Ontario, families experienced 4 provincial lockdowns and partially coinciding periods of school closure. However, long-term consequences of the pandemic on developmental outcomes in children are not fully understood, particularly for preschool-aged children who may be highly sensitive to pandemic stress given the heightened plasticity of the brain during this period.4-6 Understanding how the pandemic may have affected preschool childrens development is important for practitioners who provide care to children and families, and to acquire evidence to increase preparedness for future disasters.
Most studies in children and adolescents during the pandemic focused on socioemotional outcomes with longitudinal studies and meta-analyses suggesting that the prevalence of mental health problems increased during the pandemic compared with prepandemic levels.7-11 In contrast, few studies have examined the effects of the pandemic on childrens neurocognitive functioning. A 2022 meta-analysis12 found limited evidence for significant neurodevelopmental difficulties among infants and young children born or assessed during the pandemic compared with prepandemic children, with marginal evidence of communication problems among those assessed during the pandemic. The small number of studies in this area make it unclear whether, and to what degree, the pandemic may have adversely affected childrens neurocognitive development.
Existing studies examining pandemic effects on children have several limitations.9,13-17 These include the fact that most studies: (1) have been conducted with small and highly selected samples; (2) rely on parental reports of outcomes, which are prone to reporting biases; and (3) lack a prepandemic comparison sample or use data from historical samples that differ on key sociodemographic characteristics from the pandemic-exposed group. The current study addresses these limitations by combining assessments of socioemotional and neurocognitive development during the pandemic using both parent-report and performance-based measures with comparisons to a prepandemic cohort from the same study using matched methods and measures. Specifically, we leverage data from the Ontario Birth Study (OBS), a prospective pregnancy cohort. The OBS began prior to the pandemic and continued recruitment and follow-up during the pandemic. In the current study, we examined cross-sectional associations between general pandemic exposure vs nonexposure with child neurodevelopment at 24 months of age and neurocognitive and socioemotional functioning at 54 months of age. We hypothesized that children assessed during the pandemic would demonstrate less optimal neurodevelopmental, neurocognitive, and socioemotional outcomes at both ages compared with children assessed prepandemic.
Study Design and Participants
This cross-sectional study used data from the OBS, a prospective pregnancy study with continuous recruitment since 2013. Women receiving prenatal care at Mount Sinai Hospital in Toronto, Ontario, were recruited before 17 weeks gestation. Participants were asked to complete questionnaires that included sociodemographic and health information and to consent to the collection of clinical information.18 This study was approved by the research ethics board at Mount Sinai Hospital and followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross-sectional studies.
In 2018, a companion protocol, OBS Kids, was initiated to follow participating mothers and their liveborn children to age 54 months. Telephone follow-up was conducted at 8 and 36 months, and in-person visits were conducted at 24 and 54 months of age, when development was assessed. As of June 29, 2022, there were 2501 mother-child dyads eligible for OBS Kids. For 1545 of these, the child had reached 48 months of age; 1258 were invited to complete the 54-month follow-up, with 753 total completions and 724 completed by June 29, 2022. Twenty-one twins were excluded (1 twin of each twin pair was selected for analyses using a random number generator), leaving 703 for analyses at age 54 months. For 1346 of the eligible mother-child dyads, the child had reached age 24 months; 1140 were invited to complete the 24-month follow-up, with 762 total completions and 738 completed by June 29, 2022. Twenty twins were excluded, leaving 718 for analyses at 24 months.
The exposure was any early childhood exposure to the COVID-19 pandemic. Participants were considered part of the pandemic-exposed group if they completed assessments after March 11, 2020, the date the World Health Organization declared COVID-19 a global pandemic.19 Participants in the nonexposed group were assessed before this date, meaning they had no exposure to the pandemic at assessment. The groups were compared independently at ages 24 and 54 months with little overlap.
Developmental Assessment at 24 Months
The Ages and Stages Questionnaire, Third Edition (ASQ-3) was used to assess neurodevelopment at 24 months. The ASQ-3 is a psychometrically sound screening tool measuring communication, gross motor, fine motor, problem solving, and personal-social skills.20 For analyses, scores on the ASQ-3 were included both as continuous variables (ie, total scores for each domain [range, 0-60]) and binary variables defined by scores either below or above a standard cutoff value.20 For the latter, scores in the monitoring or below cutoff range (ie, scores requiring follow-up or referral) were combined into the at-risk category; scores above this cutoff were included in the typically developing category (with typically developing representing 0; and at-risk, 1).20
The Modified Checklist for Autism in Toddlers, Revised (MCHATR), a validated and adequately reliable screening tool for autism,20 provided an additional neurodevelopmental measure. Scores from 0 to 2 were considered low risk, while scores from 3 to 20 were considered higher risk, resulting in a binary variable (low-risk, 0; higher-risk, 1) included in analyses. The ASQ-3 and MCHAT-R were completed by mothers as part of an in-person visit or over the telephone. Before the pandemic, 22% of questionnaires were completed by phone, compared with 91% during the pandemic.
Developmental Assessment at 54 Months
Children completed the NIH Toolbox Early Childhood Cognitive Battery at age 54 months, administered on iPads during in-person visits to participants homes. The Flanker Inhibitory Control Test, Dimensional Change Card Sort (DCCS) Test, Picture Sequence Memory Test, and Picture Vocabulary Test were administered. These tasks assess inhibitory control and attention, cognitive flexibility, visual episodic memory, and language skills, respectively.21 This instrument has strong validity and reliability and has been widely used in this age group.22,23 Age-corrected standard scores with a mean (SD) score of 100 (15) were used in analyses. A Cognitive Composite score reflecting overall cognitive skills was also analyzed.24 Higher scores represented better performance for all tasks.
Mothers also completed the NIH Toolbox Emotion Battery. Before the pandemic, 8% of questionnaires were completed by phone, while 72% were completed by phone during the pandemic. The Anxiety, Negative Psychosocial Functioning, and Psychological Well-being summary scores, computed using standard methods, were used.25,26 Age- and sex-corrected T-scores (mean [SD], 50 [10]) were used in analyses.
Analyses were conducted using R version 4.2.1 (R Project for Statistical Computing). Associations between pandemic exposure vs nonexposure (reference group) and neurodevelopment were tested using either logistic or linear regression. In the logistic regression models at 24 months, the typically developing category was the reference group. At 24 and 54 months of age, linear regression was used to test the association between pandemic exposure vs nonexposure and childrens outcomes (reported as sample regression coefficient B, where a 1-unit increase in the variable is associated with a B unit increase in the outcome on the outcomes original scale). We tested both unadjusted models and adjusted models that controlled for maternal age (years), child sex (male, 0; female, 1), gestational age, birth weight, maternal race (White, 0; other race, 1), maternal birth country (Canada, 0; outside of Canada, 1), maternal education (bachelors degree or higher, 0; less than bachelors degree, 1), and household income (above $150000, 0; $150000 or less, 1). Covariates were selected based on associations with childrens cognitive and emotional development in prior studies. Information on participant race and ethnicity was self-reported and collected as part of the overall sociodemographic information collected for the OBS. Race and ethnicity was stratified as White and other or mixed race in analyses due to the small size of groups other than White. We focused on the adjusted analyses.
The distributions of ASQ-3 and NIH Toolbox cognitive scores were not consistently normal. Thus, multiple likelihood estimation, which accounts for non-normal data and is robust to skewness, was conducted with the lavaan package in R.26 A 2-sided P value <.05 was considered statistically significant.
Missing values for covariates were estimated using multivariate imputation by chained equations (MICE) using the MICE package in R. The frequency of missing data appeared to be randomly distributed (ie, the reason for missingness was not related to the outcome). Sensitivity analyses were conducted in which children with known neurodevelopmental diagnoses (eg, ASD and ADHD) were excluded. To test whether the results were robust to the analytic method chosen, we conducted additional analyses to assess whether childrens outcomes varied based on duration of pandemic exposure or proportion of ones life spent in the pandemic, as well as hierarchical linear regression models that controlled for exposure duration (eTables 4-12 in Supplement 1).
At 24 months of age, 258 children were assessed before the pandemic (April 17, 2018, to March 10, 2020) and 460 were assessed during the pandemic (March 17, 2020, to May 17, 2022) (Table 1). At 54 months of age, 417 children were assessed before the pandemic (February 8, 2018, to March 10, 2020) and 286 were assessed during the pandemic (March 14, 2020, to June 6, 2022). The mean (SD) ages were 25.6 (1.9) months and 55.4 (2.6) months, and 342 (47.6%) and 331 (47.1%) were female at each age, respectively. The 24-month and 54-month cohorts represented 2 groups of children that were assessed cross-sectionally, with 129 children who contributed data at both ages.
Most participating mothers self-identified as White (age 24 months, 461 [64.2%]; age 54 months, 487 [69.3%]) and approximately half reported a household income greater than $150000 (age 24 months, 362 [50.4%]; age 54 months, 365 [51.9%]). Additionally, 304 mothers (42.3%) in the 24-month cohort and 264 mothers (37.6%) in the 54-month cohort attended graduate or professional school. There were no sociodemographic differences between pandemic-exposed and nonexposed groups. Distributions of outcome measures are shown in Table 2.
Associations Between Pandemic Exposure and Neurodevelopment at 24 Months
The pandemic-exposed group had a significantly lower adjusted odds of problem-solving difficulties (odds ratio [OR], 0.33; 95% CI, 0.18-0.62; P=.005) but a significantly higher risk of personal-social difficulties (OR, 1.67; 95% CI, 1.09-2.56; P=.02) compared with the nonexposed group (Table 3). There were no significant differences on the MCHAT-R between groups. In adjusted models using continuous scores (Table 4), the pandemic-exposed group had significantly higher problem-solving skills (B, 3.93; 95% CI, 2.48 to 5.38; =0.21; P<.001), but lower personal-social skills (B, 1.70; 95% CI, 3.21 to 0.20; =0.09; P=.03), compared with the nonexposed group. Fine motor skills were significantly higher in the pandemic-exposed group (B, 2.18; 95% CI, 0.41 to 3.95; =0.10; P=.02). Results were similar after removing children with known neurodevelopmental diagnoses (eTables 1-3 in Supplement 1).
Associations Between Pandemic Exposure and Neurocognitive and Socioemotional Development at 54 Months
In adjusted models, the pandemic-exposed group had significantly higher vocabulary (B, 3.16; 95% CI, 0.13 to 6.19; =0.09; P=.04) and picture sequence memory scores (B, 5.95; 95% CI, 1.11 to 10.79; =0.11; P=.02) compared with the nonexposed group, as well as higher cognitive composite scores (B, 3.89; 95% CI, 0.73 to 7.04; =0.11; P=.02) (Table 5). There were no significant differences in childrens socioemotional functioning between exposed and nonexposed groups. Results were similar after removing children with neurodevelopmental diagnoses (eTables 1-3 in Supplement 1).
Additional Sensitivity Analyses
We examined duration of pandemic exposure (in days) prior to assessment, as well as the proportion of ones life spent during the pandemic (ie, length of time a child was exposed to the pandemic divided by age at assessment) (eTables 4-7 in Supplement 1). In both sets of models, longer pandemic exposure was linearly associated with better fine motor skills at 24 months (duration of pandemic: B, 0.01; 95% CI, 0.003 to 0.02; =0.003; P=.01; proportion of life in pandemic: B, 7.15; 2.47 to 11.83; =0.15; P=.003). The age 54 months cohort had no associations with outcomes.
We then conducted analyses where pandemic exposure was categorized into binned groups (eTables 8-9 in Supplement 1). At 24 months, compared with children with less than 5 months of pandemic exposure, those with 5 to 10 months exposure had lower gross motor (B, 3.19; 95% CI, 5.39 to 1.00; =0.12; P=.004) and personal-social skills (B, 2.20; 95% CI, 4.30 to 0.10; =0.09; P=.04), while those with 15 to 20 months or 20 months or more had better fine motor (15 to <20 months: B, 2.67; 95% CI, 0.19 to 5.15; =0.09; P=.04; 20 months: B, 4.93; 95% CI, 2.06 to 7.81; =0.14; P=.001) and problem-solving skills (15 to <20 months: B, 4.51; 95% CI, 2.49 to 6.53; =0.18; P<.001; 20 months: B, 2.65; 95% CI, 0.31 to 4.99; =0.09; P=.03). Higher problem solving was also observed for children with 10 to 15 months of exposure compared with those with less than 5 months exposure (B, 4.12; 95% CI, 2.35 to 5.88; =0.19; P<.001). At 54 months, children with 12 or more months exposure to the pandemic had higher picture sequence memory (B, 8.39; 95% CI, 1.88 to 14.90; =0.12; P=.01) and overall cognitive composite scores (B, 6.21; 95% CI, 1.93 to 10.50; =0.13; P=.01) compared with those with less than 6 months exposure.
Finally, hierarchical regression models that controlled for exposure duration revealed that pandemic exposure itself was associated with lower gross motor (=0.17; P=.01) and personal-social skills (=0.16, P=.01), but better problem-solving skills (=0.19; P=.003), at 24 months (eTables 10-12 in Supplement 1). At age 54 months, longer pandemic exposure was associated with better picture sequence memory (=0.13; P=.02) and cognitive composite scores (=0.13; P=.01), but not with pandemic exposure itself.
In this cross-sectional study, we examined associations between pandemic exposure vs nonexposure and developmental outcomes in preschool-aged children using a relatively large sample with sociodemographically comparable groups. At 24 months of age, children assessed during the pandemic demonstrated better problem-solving and fine motor skills, but lower personal-social skills, compared with children tested before the pandemic after adjusting for potential confounders. Results were largely consistent using categorical or continuous scores for outcomes. While there was no clear association between pandemic exposure and socioemotional functioning at 54 months of age, pandemic-exposed children demonstrated higher visual memory, vocabulary, and overall cognitive function on performance-based measures compared with nonexposed children. Sensitivity analyses generally supported the primary analyses. Results within this relatively socioeconomically advantaged sample suggest that the pandemic has not been universally associated with negative outcomes in preschool-aged children. Rather, the association between pandemic exposure and preschool childrens development is characterized by increased risk in some domains of development but apparent resilience in other domains. However, it is important to note that these results may not be representative of the experiences of all preschool-aged children and their families during the pandemic.
Prior studies using the ASQ-3 to assess associations between pandemic exposure and childrens neurodevelopment have generated mixed results,12 especially when the timing of assessment is considered. Several studies observed lower scores in some or all domains among children assessed at ages 6 or 12 months during the pandemic.27-29 In contrast, another study found very few differences in scores between prepandemic and postpandemic participants, with an advantage in problem-solving in the postpandemic group at 24 months.30 In the current study, we also observed better problem-solving skills at 24 months, in addition to better fine motor skills, among children assessed during the pandemic. This may reflect the increased individualized time and attention children received from caregivers to scaffold these skills during periods of lockdown and social distancing. However, we also showed reliable evidence for decreased personal-social skills and, less reliably, gross motor skills, among pandemic-exposed compared with nonexposed children. This may reflect the fact that children had fewer socialization experiences outside the home and less opportunity to build gross motor skills through community-based activities and play opportunities. Finally, we observed higher visual memory, vocabulary, and overall neurocognitive performance using performance-based measures at 54 months. Although unexpected, this finding may be explained in part by study sampling factors. Specifically, the current sample was more socioeconomically advantaged than the general Canadian population, which has a mean household income of CAD $68400.31 It is well known that the social and health burden experienced by families during the pandemic is not equally distributed across the population, with greater socioeconomic hardship related to worse parent and child well-being during the pandemic.32 Thus, for some families, particularly socioeconomically advantaged families, societal changes brought about by the pandemic (eg, no longer having to commute) may have resulted in less stress and more time spent with children at home. Combined with greater overall resources, these parents may have been able to provide cognitively stimulating learning environments that are well-known to foster cognitive development33-35 and buffer against the effects of adversity.36,37 Thus, the developmental advantages observed in the current study for pandemic-exposed vs nonexposed children may reflect the relatively privileged nature of our sample. Additional studies with greater representation across social, economic, and racial or ethnic categories are vital to understand the extent to which the current results generalize across diverse populations.
Although higher functioning during the pandemic was observed for several areas of development at 24 and 54 months of age, children assessed during the pandemic had lower personal-social skills at 24 months, consistent with other studies during this period.27,28,38 Sensitivity analyses suggested that concerns with social development may have been somewhat brief, with the most significant concerns for children assessed 5 to 10 months after the pandemic began compared with those assessed within 5 months. In Ontario, this period was characterized by school closures that, while not directly relevant to the preschool-aged children in our sample, was linked to increased social distancing overall among families with children. This may have contributed to an overall perception of reduced personal-social skills that eventually eased by the end of the first year of the pandemic.
In addition to limited socioeconomic variability, the results should be considered in light of additional limitations. First, the study was cross-sectional with 2 separate age cohorts (ages 24 and 54 months). Additionally, we only included children exposed to the pandemic in early childhood. In the future, we will be able to assess whether pandemic exposure prenatally confers risk to childrens development. Also, sources of resilience or social buffering were not explored and further work in this area is needed. Finally, we need to consider the potential for spurious results given the number of comparisons. We note that a number of comparisons were not independent, and we focused our interpretation on overall consistent patterns rather than individual nominally significant results.
Findings from this cross-sectional study paint a nuanced picture regarding the well-being of preschool-aged children exposed to the COVID-19 pandemic. Our results underscore both the challenges and potential areas of resilience relevant to policymakers, systems of education, and mental health professionals as they develop remediation efforts to support families with young children.
Accepted for Publication: October 4, 2023.
Published: November 16, 2023. doi:10.1001/jamanetworkopen.2023.43814
Open Access: This is an open access article distributed under the terms of the CC-BY License. 2023 Finegold KE et al. JAMA Network Open.
Corresponding Author: Mark Wade, PhD, CPsych, Department of Applied Psychology and Human Development, University of Toronto, 252 Bloor St W, Toronto, ON M5S1V6, Canada (m.wade@utoronto.ca).
Author Contributions: Dr Knight had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Finegold, Knight, Wade.
Acquisition, analysis, or interpretation of data: Finegold, Knight, Hung, Ssewanyana, Wong, Bertoni, Watson, Levitan, Jenkins, Wade.
Drafting of the manuscript: Finegold, Knight, Wade.
Critical review of the manuscript for important intellectual content: Knight, Hung, Ssewanyana, Wong, Bertoni, Adel Khani, Watson, Levitan, Jenkins, Matthews, Wade.
Statistical analysis: Finegold, Knight.
Obtained funding: Knight, Levitan, Matthews.
Administrative, technical, or material support: Bertoni, Adel Khani, Jenkins, Matthews.
Supervision: Knight, Wade.
Conflict of Interest Disclosures: Dr Matthews reported grants from Canadian Institutes for Health Research, Canada Research Chair Program, and Natural Sciences and Engineering Research Council outside the submitted work. Dr Wade reported grants from Social Sciences and Humanities Research Council of Canada, Connaught Foundation, Society for Research on Child Development, Institute for Pandemics, and American Psychological Foundation outside the submitted work. No other disclosures were reported.
Funding/Support: Funding for the Ontario Birth Study has been provided by Mount Sinai Hospital, the Sinai Health Foundation, the Lunenfeld-Tanenbaum Research Institute, and Canadian Institutes of Health Research (No. UIP-179214; principal investigator, Dr Knight).
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 2.
Additional Contributions: The authors acknowledge the contribution and support of Ontario Birth Study Team members. In addition, we thank and are extremely grateful to all of the women and children who took part in this study.
Squires J, Twombly E, Bricker DD, Potter L. ASQ-3 Users Guide. Paul H. Brookes Publishing Co; 2009.
Mpox, formerly known as monkey pox , was first identified in humans in the Democratic Republic of the Congo (DRC) in 1970, and until 1986, 95% of mpox cases reported globally came from the central African country. That pattern has changed over the last three decades, with outbreaks cropping up elsewhere in Africa and further afield, and with the viral infection most dramatically bursting its habitual boundaries during the 2022 to 2023 global outbreak.
That global outbreak has pulled focus from mpox-endemic countries, but DRC continues to struggle with a hefty mpox burden.
This year alone, the disease has spread to various provinces, reaching 159 out of 519 health zones in the country. On 25 August 2023, Dr Robert Shongo, Director of the Program for the Fight against Monkeypox and Endemic Viral Fevers, told reporters that the DRC has recorded 6,914 cases of mpox disease including 328 deaths (4.7%) since the start of the year. The most affected provinces have been Equateur, Mai Ndombe, Tshopo, Sankuru, and Maniema provinces, he said.
Behind those figures are communities struggling under a complex social and epidemiological pressure.
Mpox, which causes fevers and scabbing rashes, progressing to death in a minority among severe cases, is a visible and consequently easily stigmatised viral disease.
Local community members and health workers who have witnessed the diseases devastating effects have been psychologically affected. A health worker in Kinshasa who has been hospitalised with the disease explained, The fear of mpox looms over us daily. We've heard stories about people dying across the country and it was emotionally hard to handle.
He continued: The fear and stigma associated with mpox have hindered our efforts. People are hesitant to seek medical attention, and misinformation spreads rapidly.
Meeting the challenges presented by the mpox epidemic in DRC is not easy. For one, the viral infection is just one among several large-scale health emergencies, including recurrent epidemics of measles, yellow fever and other life-threatening illnesses.
Insecurity, health system limitations and logistical constraints limit access to care for the population. The country extends over a vast territory, and its geography imposes challenges to the work of humanitarian and health teams. It sometimes takes several days to reach remote villages in certain regions. While WHO recommends a ratio of 1 doctor per 1,000 people, DRC has only about 0.09 doctors per 1,000 inhabitants.
With limited resources, the system struggles to meet the demands of an escalating crisis. Dr Roy Ndenge, a surveillance agent with the national programme tasked with curtailing mpox, told VaccinesWork, over the phone in October: Hospitals in some of the most affected areas are at capacity due to the presence of other epidemics, and medical professionals are working tirelessly to provide care.
In Kinshasa, where a few cases were reported in August, five mpox patients had been recently released from hospital, Ndenge said. Those cases included three people who had been transferred to hospital in the capital from Maindombe province in August, and two contacts that had fallen sick in Kinshasa.
The response to mpox has evolved over time. Early in 2023, containment efforts were met with logistical challenges, including vaccine distribution and healthcare infrastructure limitations. In the beginning, health staff faced shortages of essential supplies and vaccines. However, current efforts have seen improvements, with international organisations and NGOs stepping in to provide crucial support. Said Dr Ndenge, The assistance from NGOs like Mdecins Sans Frontires (MSF) has been instrumental. We now have better access to supplies, and our teams are more equipped to handle cases.
Dr Thomas Holebanga, Medical Activity Manager at MSFs Congo Emergency Pool (PUC) said before the arrival of MSF teams in August 2023, the health zone of Bolomba in the Equateur province recorded the most cases of illness, and many deaths. That was due in part, he explained, to technical, logistical, financial limitations, as well as to socio-economic factors among the affected communities, including poverty, promiscuity or ignorance of the disease.
Beyond putting in place infection prevention and control measures in health structures, MSF also implemented a home isolation strategy, he said, which allowed patients without complications to be treated in their houses. A hygiene kit was provided to them and their loved ones with advice on the use of these kits in order to cut the chain of transmission.
Regular monitoring of these cases was carried out by MSF teams with the support of community workers. All of these strategies have made it possible to significantly reduce the number of cases and deaths, said Dr Holebanga. From 1,781 cases and 216 deaths reported as of August 2023, the number of cases went to 891 and 4 deaths in October.
Meanwhile, the World Health Organization (WHO) is raising awareness and mobilising resources for the response as part of the One Health approach.
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In 2020, people wanted a way to tell if they might have been exposed to COVID-19.
More than 20 states in the U.S., including Pennsylvania and Delaware, used a smartphone app that applied existing bluetooth technology to keep track of how far away someone was from another person who had the app. It also sent out alerts if those people later reported themselves as having COVID-19. Each state had their own version of the app.
In the U.S. people were not required to use these apps, and few did, making them less effective than in other countries. But experts say public health authorities in the U.S. can still learn from the experience and be more prepared the next time a pandemic happens.
The Association of Public Health Laboratories managed the exposure notification program for states in the U.S. that used an app to warn people about exposure to COVID-19. Senior consultant Emma Sudduth said they were excited about this in the beginning.
Every time a friend or family in another state received an exposure notification, I was always told, and I was always very proud to hear that they had gotten a notification that they were delaying their trip to visit their grandma, that they were going to start testing, that they were monitoring.
She said the association estimates that around 10% of the entire U.S. population, millions of people, downloaded an exposure notification app. But this was not enough for these apps to be broadly effective.
We were building the plane while we were flying it, so to speak, Sudduth said.
Earlier this year, researchers at the Centers for Disease Control and Prevention worked with Pennsylvania health officials to study how much of a difference the app made in Pennsylvania. They found that from the end of 2020 to the start of 2021, around 5% of the people they surveyed had downloaded the app. Of the people who tested positive for COVID-19 in their survey, only 0.2% of people had installed the app.The researchers concluded this limited how effective the app could have been.
Joanna Masel, an evolutionary biologist at the University of Arizona, helped develop an app for her university, and the state of Arizona. She said it helped reduce transmission on campus by making a real but modest impact.
She added that exposure notification apps will probably be effective in the U.S. in places like that smaller, tightly connected communities like workplaces, colleges, and schools, where people can also be more consistently and quickly tested.
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A coronavirus uses protein "spikes" to grab and infect cells. Despite their name, those spikes aren't stiff and pointy. They're shaped like chicken drumsticks with the meaty part facing out, and the meaty part can tilt every which way on its slender stalk. That ability to tilt, it turns out, affects how successfully the spike can infect a cell.
Now researchers from the Department of Energy's SLAC National Accelerator Laboratory and Stanford University, along with collaborators at three more universities, have obtained high-resolution images of intact coronavirus spikes on the surfaces of virus particles; identified a tiny hinge surrounded by sugar molecules that allows the spike's glob-like "crown" to bend on its stalk; and measured how far it can tilt in any direction.
While the study was carried out on a much less dangerous cousin of SARS-CoV-2, the coronavirus that causes COVID-19, it has implications for COVID-19, too, since both viruses bind to the same receptor on a cell's surface to initiate infection, said Jing Jin, a biologist at Vitalant Research Institute and adjunct assistant professor at the University of California, San Francisco who performed virology experiments for the study.
The results, she said, suggest that disabling the spike's hinges could be a good way to prevent or treat a wide range of coronavirus infections.
The team also discovered that each coronavirus particle is unique, both in its underlying shape and its display of spikes. Some are spherical, some are not; some bristle with spikes while others are nearly bald.
"The spikes are floppy and move around, and we used a combination of tools to explore all their possible angles and orientations," said Greg Pintilie, a Stanford scientist who developed detailed 3D models of the virus and its spikes. Seen up close, he said, each spike is different from all the rest, mainly in its direction and degree of tilting.
The research team reported its findings in Nature Communications.
"Since the pandemic started, most studies have looked at the structures of coronavirus spike proteins that were not attached to the virus itself," said Wah Chiu, a professor at SLAC and Stanford and co-director of the Stanford-SLAC Cryo-EM facilities where the imaging was done. "These are the first images made of the spikes of this strain of coronavirus while they're still attached to the virus particles."
The study has roots in the early days of the pandemic, when research at SLAC shut down except for work aimed at understanding, preventing and treating COVID-19 infections.
Because experiments with the actual SARS-CoV-2 virus can only take place in high-level (BSL3) biosafety labs, many scientists chose to work with more benign members of the coronavirus family. Chiu and his colleagues selected human coronavirus NL63 as their subject. It causes up to 10% of human respiratory infections, mainly in children and immunocompromised people, with symptoms ranging from mild coughs and sniffles to bronchitis and croup.
In 2020, Chiu said, the team used cryogenic electron microscopy (cryo-EM) and computational analysis to image the crowns of NL63 spikes with near-atomic resolution.
But because a spike's stalk is much thinner than its crown, they were not able to get clear, high-resolution images of both at once.
This study combined information gleaned from a series of experiments to get a much more complete picture.
First, Stanford graduate student David Chmielewski used cryogenic electron tomography (cryo-ET) to combine cryo-EM images of viruses that were taken from different angles into high-resolution 3D images of more than a hundred NL63 particles.
SLAC senior scientist Michael Schmid plugged those images into a 3D visualization tool and discovered that each of a particle's spikes was bent in a unique way. Another SLAC scientist, Muyuan Chen, used advanced image reconstruction to create maps showing the average density of the spikes' crowns and stalks.
Zooming in on one of those spikes, biological chemist Lance Wells at the University of Georgia used a technique called mass spectrometry to pinpoint the site-specific chemical compositions of the 39 sugar chains attached to each of the spike's three identical proteins.
Finally, Abhishek Singharoy, a computational biophysicist at Arizona State University, and his student, Eric Wilson, integrated all those measurements into atomic models of the spikes' crowns and stalks at different bending angles, and carried out further simulations to see how far and how freely a spike can bend.
"It turns out that no matter what, the spikes have a preferred bending angle of about 50 degrees," Chiu said, "and they can tilt up to 80 degrees in any direction in the simulation, which matches well with our cryo-ET experimental observations."
The bending occurred at a place on the stalk, just below the crown, where a particular cluster of sugar molecules clung to the protein, forming a hinge. Computer simulations suggested that changes in the structure of this hinge would affect its ability to bend, and lab experiments went one step further: They showed that mutations in the protein part of the hinge made the spike much less infectious. This suggests that targeting the hinge could provide an avenue to fight the virus.
"People working on the more dangerous coronaviruses, including MERS-CoV and SARS-CoV-2, have identified a region equivalent to this one and discovered antibodies targeting this region," Jin said. "That tells us it's a critical region that is highly conserved, meaning that it has stayed much the same over the course of evolution. So maybe by targeting this region in all coronaviruses, we can come up with a universal therapy or vaccine."
More information: David Chmielewski et al, Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans, Nature Communications (2023). DOI: 10.1038/s41467-023-42836-9
Journal information: Nature Communications
Covid and flu shots can be safely given at the same time, and according to a small new study, doing so may even confer benefits.
Findings presented Monday at the Vaccines Summit Boston, an annual scientific conference, suggest that giving Covid and flu shots together could produce a stronger antibody response against the coronavirus than administering the vaccines separately.
The study measured the antibody levels of 42 health care workers in Massachusetts who were vaccinated last fall. Twelve of the participants received a bivalent Covid booster and seasonal influenza shot on the same day. Another 30 received the shots on different days within the span of a month.
Three to four weeks after people got their Covid boosters, those who had received the flu shot at the same time had higher levels of IgG1, an antibody involved in the body's front-line defense against Covid. The results held true six months later, suggesting that co-administering the vaccines could improve long-term protection.
We showed that the Covid antibody responses were higher and more durable if the Covid and flu vaccines were given on the same day, said Susanna Barouch, the studys lead author and an intern at the Ragon Institute's Systems Serology Lab in Cambridge, Massachusetts.
The research is undergoing peer review and has not been published in a scientific journal. Ryan McNamara, the lab's director and senior author on the study, said the findings still need to be replicated in a larger group of volunteers, but he felt it was useful to share the results right away. In September, the findings were posted to the preprint server BioRxiv.
"We thought that these findings were very important for immediate public health decision making," McNamara said.
He expects the results to apply to this years updated Covid vaccines, he added, though his team plans to explore that further.
The Centers for Disease Control and Prevention recommends getting Covid and flu vaccines at the same appointment if people are eligible for both shots at once. But that recommendation is based on convenience rather than efficacy, said Dr. Judith ODonnell, chief of infectious diseases at Penn Presbyterian Medical Center in Philadelphia, who wasnt part of the study.
We probably would want to see this kind of data replicated using the current 2023 vaccines to really know with 100% certainty how giving those together might enhance immunity or not, she said.
McNamara said it's still unclear why getting Covid and flu shots together might result in stronger, more lasting protection.
One theory, he said, is that most people's bodies are already primed to produce Covid antibodies because they've been vaccinated or exposed to the virus before. Giving two vaccines at once could awaken this immune response to a greater extent than one shot alone, which may lead to more a robust antibody response, he said.
"Your immune system is a highly tuned army and its basically calling all the special forces at the same time," said Dr. Michelle Barron, senior medical director of infection prevention and control at UCHealth in Colorado, who was not involved in the research.
But that strong immune response could also induce greater side effects, she added. In a 2022 study, getting a Covid booster and flu shot together was associated with an 8% to 11% higher rate of self-reported side effects like fatigue, headache and muscle pain in the week after vaccination compared to getting a Covid booster alone.
An October analysis from the Food and Drug Administration, which has not been peer-reviewed, also identified a slightly elevated risk of stroke among people ages 85 and up who had received a high-dose flu shot at the same time as a bivalent Covid vaccine.
Dr. Scott Roberts, an infectious disease specialist at Yale Medicine, said it's possible that "we're starting to see the immune system revved up so much that we're seeing these inflammatory conditions like stroke in this select age group."
But Barron noted that many older people have underlying health conditions that independently increase their risk of stroke, and several other studies have not identified the same safety concern with co-administering Covid and flu shots.
"The benefit of getting the shots and knowing that you have that protection will outweigh any of these potential risks," she said.
The CDC recommends getting a flu shot by the end of October. As of Monday, however, less than 33% of children and less than 35% of adults in the U.S. had gotten their flu shots, according to CDC data.
Uptake of Covid shots is even lower this year: 5% of children and 14% of adults have received the updated Covid vaccine.
ODonnell said its reasonable for people to want to space out their shots to lower the risk of side effects. While the CDC does not recommend a certain waiting period between vaccines, ODonnell suggested for people who prefer to space them out, separating the shots by a couple weeks.
But infectious disease experts widely agreed that co-administration may be the best option at this point, since the vaccines take two weeks to be fully effective and both Covid and flu are spreading in the U.S.
Covid hospital admissions fell 8% nationally the week ending Nov. 4, but theyre rising in many individual counties. Flu-related hospital admissions also rose 20% in that time, while the number of positive flu tests rose 50%.
"We've been seeing increases in Covid and now we're seeing increases in flu," Barron said. "Theres really no value in saying, Oh, Ill wait another week, because thats another week where, whichever vaccine you didnt get, youre now potentially vulnerable."
Aria Bendix is the breaking health reporter for NBC News Digital.
