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Microbiology

Memory B cell marker predicts long-lived antibody response to flu vaccine

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Memory B cells play a critical role to provide long-term immunity after a vaccination or infection. In a study published in the journal Immunity, researchers describe a distinct and novel subset of memory B cells that predict long-lived antibody responses to influenza vaccination in humans.

These effector memory B cells appear to be poised for a rapid serum antibody response upon secondary challenge one year later, Anoma Nellore, M.D., Fran Lund, Ph.D., and colleagues at the University of Alabama at Birmingham and Emory University report. Evidence from transcriptional and epigenetic profiling shows that the cells in this subset differ from all previously described memory B cell subsets.

The UAB researchers identified the novel subset by the presence of FcRL5 receptor protein on the cell surface. In immunology, a profusion of different cell-surface markers is used to identify and separate immune-cell types. In the novel memory B cell subset, FcRL5 acts as a surrogate marker for positive expression of the T-bet transcription factor inside the cells. Various transcription factors act as master regulators to orchestrate the expression of many different gene sets as various cell types grow and differentiate.

Nellore, Lund and colleagues found that the FcRL5+ T-bet+ memory B cells can be detected seven days after immunization, and the presence of these cells correlates with vaccine antibody responses months later. Thus, these cells may represent an early, easily monitored cellular compartment that can predict the development of a long-lived antibody response to vaccines.

This could be a boon to the development of a more effective yearly influenza vaccine. “New annual influenza vaccines must be tested, and then manufactured, months in advance of the winter flu season,” Lund said. “This means we must make an educated guess as to which flu strain will be circulating the next winter.”

Why are vaccine candidates made so far in advance? Pharmaceutical companies, Lund says, need to wait many weeks after vaccinating volunteers to learn whether the new vaccine elicits a durable immune response that will last for months. “One potential outcome of the current study is we may have identified a new way to predict influenza vaccine durability that would give us an answer in days, rather than weeks or months,” Lund said. “If so, this type of early ‘biomarker’ could be used to test flu vaccines closer to flu season — and moving that timeline might give us a better shot at predicting the right flu strain for the new annual vaccine.”

Seasonal flu kills 290,000 to 650,000 people each year, according to World Health Organization estimates. The global flu vaccine market was more than $5 billion in 2020.

To understand the Immunity study, it is useful to remember what happens when a vaccinated person subsequently encounters a flu virus.

Following exposure to previously encountered antigens, such as the hemagglutinin on inactivated influenza in flu vaccines, the immune system launches a recall response dominated by pre-existing memory B cells that can either produce new daughter cells or cells that can rapidly proliferate and differentiate into short-lived plasmablasts that produce antibodies to decrease morbidity and mortality. These latter B cells are called “effector” memory B cells.

“The best vaccines induce the formation of long-lived plasma cells and memory B cells,” said Lund, the Charles H. McCauley Professor in the UAB Department of Microbiology and director of the Immunology Institute. “Plasma cells live in your bone marrow and make protective antibodies that can be found in your blood, while memory B cells live for many years in your lymph nodes and in tissues like your lungs.

“Although plasma cells can survive for decades after vaccines like the measles vaccine, other plasma cells wane much more quickly after vaccination, as is seen with COVID-19,” Lund said. “If that happens, memory B cells become very important because these long-lived cells can rapidly respond to infection and can quickly begin making antibody.”

In the study, the UAB researchers looked at B cells isolated from blood of human volunteers who received flu vaccines over a span of three years, as well as B cells from tonsil tissue obtained after tonsillectomies.

They compared naïve B cells, FcRL5+ T-bet+ hemagglutinin-specific memory B cells, FcRL5neg T-betneg hemagglutinin-specific memory B cells and antibody secreting B cells, using standard phenotype profiling and single-cell RNA sequencing. They found that the FcRL5+ T-bet+ hemagglutinin-specific memory B cells were transcriptionally similar to effector-like memory cells, while the FcRL5neg T-betneg hemagglutinin-specific memory B cells exhibited stem-like central memory properties.

Antibody-secreting B cells need to produce a lot of energy to churn out antibody production, and they also must turn on processes that protect the cells from some of the detrimental side effects of that intense metabolism, including controlling the dangerous reactive oxygen species and boosting the unfolded protein response.

The FcRL5+ T-bet+ hemagglutinin-specific memory B cells did not express the plasma cell commitment factor, but did express transcriptional, epigenetic and metabolic functional programs that poised these cells for antibody production. These included upregulated genes for energy-intensive metabolic processes and cellular stress responses.

Accordingly, FcRL5+ T-bet+ hemagglutinin-specific memory B cells at Day 7 post-vaccination expressed intracellular immunoglobulin, a sign of early transition to antibody-secreting cells. Furthermore, human tonsil-derived FcRL5+ T-bet+ memory B differentiated more rapidly into antibody-secreting cells in vitro than did FcRL5neg T-betneg hemagglutinin-specific memory B cells.

Lund and Nellore, an associate professor in the UAB Department of Medicine Division of Infectious Diseases, are co-corresponding authors of the study, “A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans.”

Co-authors with Lund and Nellore are Esther Zumaquero, R. Glenn King, Betty Mousseau, Fen Zhou and Alexander F. Rosenberg, UAB Department of Microbiology; Christopher D. Scharer, Tian Mi, Jeremy M. Boss, Christopher M. Tipton and Ignacio Sanz, Emory University School of Medicine, Atlanta, Georgia; Christopher F. Fucile, UAB Informatics Institute; John E. Bradley and Troy D. Randall, UAB Department of Medicine, Division of Clinical Immunology and Rheumatology; and Stuti Mutneja and Paul A. Goepfert, UAB Department of Medicine Division of Infectious Diseases.

Funding for the work came from National Institutes of Health grants AI125180, AI109962 and AI142737 and from the UAB Center for Clinical and Translational Science.

  • Anoma Nellore, Esther Zumaquero, Christopher D. Scharer, Christopher F. Fucile, Christopher M. Tipton, R. Glenn King, Tian Mi, Betty Mousseau, John E. Bradley, Fen Zhou, Stuti Mutneja, Paul A. Goepfert, Jeremy M. Boss, Troy D. Randall, Ignacio Sanz, Alexander F. Rosenberg, Frances E. Lund. A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans. Immunity, 2023; DOI: 10.1016/j.immuni.2023.03.001

    • University of Alabama at Birmingham
    Microbiology

    Biologists, chemical engineers collaborate to reveal complex cellular process inside petunias

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    Once upon a time, prevailing scientific opinion might have pronounced recently published research in Nature Communications by a team of Purdue University scientists as unneeded. Now, climate change implications have heightened the need for this line of research.

    Flowers emit scent chemicals called volatile organic compounds (VOCs). Earlier this year, the Purdue team published the paper identifying for the first time a protein that plays a key role in helping petunias emit volatiles. The article was selected for the “plants and agriculture” section of the journal’s editors’ highlights webpage.

    Natalia Dudareva, who led the study, and her longtime collaborator John Morgan had suggested years ago in grant proposals that molecular processes could be involved in VOC emission. Both times the grant reviewers said there was nothing to look for because simple diffusion was the answer.

    “We failed twice because people did not believe us,” said Dudareva, director of the Center for Plant Biology and Distinguished Professor of Biochemistry. “We decided we have to have proof that it’s not simple diffusion, that molecular mechanisms are involved.”

    The new work builds on findings that the Dudareva-Morgan collaboration announced in 2015 and 2017 showing how biology helps control the release of scent compounds from plants. The latest paper, chiefly funded by the National Science Foundation and the U.S. Department of Agriculture, focuses on how volatiles cross the cell wall, the barrier that separates the cellular interior from a plant’s outermost protective layer, the cuticle.

    “We were looking at whether or not there are proteins that facilitate the transport of these small organic molecules across the cell wall layer,” said Morgan, a professor of chemical engineering.

    “The best analogy is to the transport of oxygen in muscle tissue by a protein called myoglobin.”

    Volatile organic chemicals are small molecules that have low water solubility. The cell wall, however, is a water-filled environment. This slows the diffusion rate of VOCs because their concentrations cannot build up very high.

    “What happens is a protein can bind a lot of these molecules inside a non-waterlike cavity, and it improves or increases the net transport rate,” Morgan explained.

    The work has significant practical implications, ranging from the health of the planet to industrial operations. Plants now emit 10 billion metric tons of carbon annually, a quantity that will increase with continued global warming. Floral volatiles also help to protect plants against environmental stresses and are heavily used in the cosmetics industry and in aromatherapy.

    “And our diet depends on insect-pollinated plants,” Dudareva said. With global warming, flowers may start blooming earlier, before insects are ready to begin pollination.

    The team’s 2015 paper published in the journal Trends in Plant Science reported calculations that had determined the concentration of volatiles needed to sustain the experimentally measured floral emission rate. The concentration reached the millimolar range, a scale that chemists use to quantify substances containing huge numbers of molecules or atoms.

    “These compounds will accumulate inside membranes and such high concentration will destroy membranes and destroy the cell,” Dudareva said. This left a clear-cut conclusion: simple diffusion would be impossible.

    The initial work had been calculated for snapdragons. But the Purdue researchers focused on petunias for their latest study because, unlike snapdragons, they can be genetically modified to study how particular genes affect the emission process.

    “It’s much easier to work with petunias because emission is high, especially during the night,” said Pan Liao, a lead co-author and former Purdue postdoctoral scientist, now an assistant professor of biology at Hong Kong Baptist University. “The emission is strongly regulated in a diurnal pattern.”

    Additional co-authors were Itay Maoz, a former Purdue postdoctoral scientist now of Israel’s Agricultural Research Organization; Meng-Ling Shih, PhD 2022, chemical engineering; Xing-Qi Huang, a postdoctoral scientist working in Dudareva’s lab; and Ji Hee Lee, a graduate student in biochemistry. The co-authors contributed a complementary blend of skills and expertise to the work that has become a hallmark of the longstanding collaboration between the Dudareva and Morgan research groups.

    Dudareva’s group generated the transgenic plants and handled the cellular biology needed to determine whether a given protein contributes to the volatile emissions. There is no way, however, to detect the level of proteins in a cell or how their concentration changes across a cell wall.

    It then fell to Morgan’s group to perform the calculations that quantified the protein contributions and conduct computer simulations to verify the experimental data.

    “It’s important to have feedback between the modeling predictions and the actual data,” Morgan said. “Sometimes it starts with the data, then we go do math, and then we go back and compare to the data.”

  • Pan Liao, Itay Maoz, Meng-Ling Shih, Ji Hee Lee, Xing-Qi Huang, John A. Morgan, Natalia Dudareva. Emission of floral volatiles is facilitated by cell-wall non-specific lipid transfer proteins. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-36027-9

    • Purdue University
    Microbiology

    How do parents decide if they should vaccinate their kids against SARS-CoV-2?

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    For parents, the decision to vaccinate their kids against SARS-CoV-2 is complex, influenced by scientific evidence, political and social pressures, and views about individual versus collective benefits of vaccination, according to a new study published in CMAJ (Canadian Medical Association Journal).

    Researchers conducted a qualitative study with in-depth interviews of 20 parents to understand their views about SARS-CoV-2 vaccination, with a goal to support future vaccination initiatives.

    “Given the observed discrepancy between parental intention and decision to vaccinate their children against SARS-CoV-2, it is important to understand how and why parents make their decisions,” said Dr. Jonathon Maguire, a pediatrician at St. Michael’s Hospital, a site of Unity Health Toronto, and the University of Toronto. “Understanding the factors that influence parents’ decisions about SARS-CoV-2 vaccination for their children would help improve and interventions as well as inform about parents’ perspectives and concerns.”

    Few previous studies have explored how parents make decisions to vaccinate, or not vaccinate, their children once eligible for vaccination.

    The decision was challenging for most parents in the study. Parents’ considerations related to the following:

    These findings have implications for communicating information on SARS-CoV-2 vaccination.

    “Future guidance should highlight both individual and collective benefits of SARS-CoV-2 vaccination for children; however, health care providers should prioritize individualized discussions with parents to help interpret evidence, consider their understanding of risks and benefits, and provide tailored recommendations,” said Dr. Janet Parsons, a research scientist at St. Michael’s Hospital, a site of Unity Health Toronto, and an associate professor at the University of Toronto.

    Health care providers have a key role to play in supporting parents in decision making.

    “It is important for health care providers to understand that parents who seem hesitant to vaccinate their children may have a variety of reasons for feeling this way and may be reticent to ask questions to for fear of stigma,” said Dr. Parsons. The authors recommend that these conversations be approached with empathy and openness.

    More information:
    Parents’ perspectives on SARS-CoV-2 vaccinations for children: a qualitative analysis, Canadian Medical Association Journal (2023). DOI: 10.1503/cmaj.221401

    Journal information:
    Canadian Medical Association Journal

    Canadian Medical Association Journal

    Science X Network

    Microbiology

    Three doses of COVID-19 mRNA vaccine associated with better outcomes for patients with cancer

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    Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern and patients with cancer are highly vulnerable and susceptible to poor outcomes.

    It is recommended that with receive a 3-dose COVID-19 vaccination series but it is noted that their immunological response to the vaccine series may be lessened, notably among those with hematologic malignancies.

    Utilizing data from the multi-institutional COVID-19 and Cancer Consortium (CCC19) scientists found vaccination with 2 or 3 doses of an mRNA vaccine prior to infection was associated with improved outcomes for patients with cancer diagnosed with COVID-19 in 2021 or 2022. Across all endpoints, including 30-day morality, ICU admission and hospitalization, the vaccine benefit was most pronounced for those patients receiving 3 doses.

    This study shows vaccination against COVID-19 is an essential strategy to improve outcomes in this high-risk population. The results support guidelines that patients with cancer should receive at least 3 COVID-19 vaccine doses.

    This analysis represents one of the largest cohorts with comprehensive clinical and on vaccinated patients with cancer and breakthrough COVID-19 to date and is one of the first studies to evaluate breakthrough infections following the receipt of 3 doses of mRNA vaccines among patients with cancer.

    The findings are published in The Lancet Regional Health—Americas.

    More information:
    Toni K. Choueiri et al, Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium, The Lancet Regional Health—Americas (2023). DOI: 10.1016/j.lana.2023.100445

    Dana-Farber Cancer Institute

    Science X Network

    Microbiology

    Flu vaccination rate holds steady but misinformation about flu and COVID-19 persists

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    Although the public had been alerted that this winter could be a potentially bad flu season, barely half of Americans said in January that they had received a flu shot, a vaccination level unchanged in a representative national panel from the comparable period last year, according to a new Annenberg Science Knowledge (ASK) survey by the Annenberg Public Policy Center of the University of Pennsylvania.

    The panel survey, fielded with over 1,600 U.S. adults, finds that many have a base of knowledge about the flu but there is a reservoir of uncertainty about other consequential information about the flu, COVID-19, and vaccination. Among the findings of the ASK survey, which also inquired more broadly about attitudes toward mandates and the continuing “return to normal”:

    “Although the CDC indicated that seasonal flu activity is now low nationally, the fact that the level of reported flu vaccination in our panel was roughly the same in January of this year as a year before is concerning,” said Kathleen Hall Jamieson, director of the Annenberg Public Policy Center. “Because this has been a more severe flu season than the one a year ago, we expected an increase in the reported vaccination rate.”

    The nationally representative panel of 1,657 U.S. adults surveyed by SSRS for the Annenberg Public Policy Center (APPC) of the University of Pennsylvania from January 10-16, 2023, was the tenth wave of an Annenberg Science Knowledge survey whose respondents were first empaneled in April 2021. The margin of sampling error (MOE) is ± 3.2 percentage points at the 95% confidence level. See the Appendix and Methodology for question wording and additional information.

    What the public knows: The flu and flu shot

    The latest wave of the ASK survey finds that many people know the basics about the flu:

    A majority of the public knows that the following claims are false:

    But there are important claims about the flu that substantial parts of the public are confused about:

    The ASK survey in January 2023 finds that 49% of respondents say they have had a seasonal flu shot, statistically unchanged from 47% in our January 2022 survey and 50% in April 2021. According to the Centers for Disease Control and Prevention (CDC), nearly 46% of U.S. adults 18 and older had a as of December 31, 2022.

    The CDC actively promoted flu vaccination amid concerns that the 2022-23 season would be severe.

    When the 49% of survey respondents who said they got the flu vaccine were asked in January why they got the shot (multiple responses were permitted):

    Worries about family members contracting flu, COVID, or RSV: About a third of those surveyed say they are somewhat or very worried about family members contracting COVID-19 (36%), the seasonal flu (35%), or RSV, respiratory syncytial virus (33%). Only 11% say they are somewhat/very worried about a family member contracting polio, which reemerged as a public health threat in July 2022 after a case was reported in New York State.

    Myocarditis: Rare cases of myocarditis, an inflammation of the heart muscle, have been reported among those who have had mRNA COVID-19 vaccines, particularly young males following a second vaccine dose. The connection between myocarditis and the vaccine has drawn attention on and in news media.

    The survey found that over a third of respondents (37%) think that COVID-19 poses a higher risk for myocarditis than the vaccine against COVID-19. But 17% think that is false and nearly half of those surveyed (47%) are not sure which poses a higher risk.

    Much of the public rejects the notion that Damar Hamlin’s collapse during an NFL game had anything to do with the vaccine against COVID-19. But the survey finds that many people are uncertain about the broader unsupported claim that more young athletes are dying of heart problems these days.

    Hamlin, a safety on the Buffalo Bills, suffered a cardiac arrest during the Jan. 2, 2023, game against the Cincinnati Bengals, triggering a spate of unfounded, anti-vaccine conspiracy theories on social media about the cause. The overwhelming majority of those in our survey (87%) said they had heard, read, or seen reports of his collapse.

    But those respondents overwhelmingly reject the idea that a COVID-19 vaccine caused Hamlin’s injury. Only 10% of those who had heard of the incident attribute it to factors connected with the vaccine. Nearly half (49%) say that based on what they had heard of it, Hamlin’s cardiac arrest was most likely caused by being hit hard in the chest; 17% say an underlying heart condition; and 21% say they are not sure.

    While social media posts with millions of views quickly associated Hamlin’s collapse with vaccination, mainstream media sources noted the lack of evidence for such claims or dismissed them as misinformation.

    However, 26% of those surveyed say they think that the number of young athletes dying of heart problems increased over the past three years, and nearly half (49%) are not sure whether the number has increased or decreased. Only 23% say that the numbers of deaths have remained virtually unchanged.

    Schools and military: The ASK survey finds stronger support for a COVID-19 vaccine mandate in the military than in public schools, with over half supporting a military mandate:

    MMR vaccine: Asked their views on the childhood vaccines for measles, mumps, and rubella (MMR), 63% agree that healthy children should be required to get the MMR vaccine in order to attend public schools, while 22% say parents should be able to decide whether to vaccinate their children who attend public schools and 15% are not sure.

    Getting back to ‘normal’

    The return to normal: Asked when they expect to be able to return to “your normal, pre-COVID-19 life,” more than half of Americans (52%) say they already have—up from 47% in October 2022. More than 1 in 5 Americans (22%) continue to say “never,” which is statistically unchanged since July 2022.

    Mask-wearing: Six in 10 people (61%) say they never or rarely wear masks, statistically unchanged from the 60% who said this in October 2022. And 18% say they always or often wear a mask, also statistically unchanged from the 17% who said so in October.

    More information:
    Survey site: www.annenbergpublicpolicycente … e-communication/ask/

    Science X Network

    Microbiology

    More than 100 years after the first TB vaccine, why are we still waiting for a second?

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    It has been more than 100 years since the first and only tuberculosis (TB) vaccine—the Bacillus Calmette–Guérin (BCG) vaccine—was used for the first time medically in 1921. With an estimated 1.6 million people dying from TB in 2021, there is an urgent need for new vaccines to help stem the never-ending pandemic.

    There are more than 10 TB vaccines currently in development, with some now in the later stages of the clinical trials process. In a presentation in one of the preliminary pre-ECCMID days of this year’s European Congress on Clinical Microbiology & Infectious Diseases (ECCMID 2023, Copenhagen, April 15-19) Frank Cobelens, Professor of Global Health at the University of Amsterdam and the Amsterdam Institute for Global Health and Development (AIGHD), Netherlands, will discuss the frontrunners among the , and the challenges facing TB development.

    “In order to reach the WHO’s target of ending TB as a global health problem, we desperately need an effective and safe vaccine for use in adults and adolescents,” explains Prof Cobelens.

    “However, TB vaccine research and development is hampered by our limited knowledge of protective immune responses, poor prediction of efficacy in humans by animal models and lack of correlates of protection (the immune response required to give protection), all leading to a high-risk pipeline that includes large trials of long duration. Essentially, we don’t know if vaccines will work until they are at the end of the clinical trials process—meaning high-risk, high cost.”

    Despite this, for the first time since decades there are several promising new TB vaccine candidates entering phase 3 trials (efficacy testing in humans), even though 2 of the 4 (VPM1002 and MTBVAC) are still live-attenuated vaccines just as BCG is– and for which the added value in terms of protection and safety over BCG is yet to be established.

    “However, the current need for long trials implies that licensure of any of these candidates will take at least several years,” says Prof Cobelens. He adds that a key issue for WHO in licensing any new TB vaccine is evidence of prevention of disease (POD)—however many of the current trials are looking at prevention of infection (POI) or prevention of recurrence (POR) in those with latent infection—which are not quite the same as POD.

    Prof Cobelens will highlight that, for the first time in decades there is a different platform candidate that has shown protection in adults and adolescents in a phase II trial: M72/ASO1E (an adjuvanted subunit vaccine). This is also important because it allows the field to identify correlates of protection. In a trial of some 3500 participants in Kenya, South Africa, and Zambia, the vaccine demonstrated 50% protection against TB infection after three years follow-up. It was also safely tested in 400 people living with HIV.

    This vaccine, licensed by pharmaceutical company GlaxoSmithKline to the Bill & Melinda Gates Medical Research Institute, is now going to enter a phase III trial in high-incidence settings across Africa, with an estimated 26,000 participants. It will include people never infected with TB and those with latent TB to see if they are protected from TB disease. But as the trial will require three years for recruitment and five for follow up, it is unlikely to provide results until the start of the 2030s.

    Other vaccines considered frontrunners include the Russian Vaccine GamTBVac, currently in a phase 3 trial with 7000 participants expected to report in or around 2025. Also considered promising is the VPM1002 (live recombinant BCG), which is about report on trials on prevention of infection in babies and prevention of recurrence in adults in the next two years (delayed due to COVID pandemic)–while a further phase 3 trial, to test prevention of infection in adult household contacts of primary infected persons, is currently underway.

    Another genetically modified live-attenuated vaccine, MTBVAC, has just begun a BCG-controlled phase 3 trial in babies in South Africa and Madagascar, while a phase 3 trial in BCG-vaccinated and unvaccinated adults is in its planning stages. Results from these trials are likely to be announced at the end of this decade.

    “We have waited more than a century for a new effective TB vaccine, and unfortunately that wait is set to last at least several more years,” concludes Prof Cobelens.

    “However, there are promising new approaches that include alternative routes of delivery for BCG-vectored vaccines that will hopefully enter the development pipeline soon. We are also in the early stages of harnessing the vaccine innovation that emerged during the COVID pandemic—which could open the door on other new routes to a successful TB vaccine.”

    More information:
    2022 Global TB report

    Science X Network

    Microbiology

    Good News: Most Long COVID Effects Resolve Within a Year After a Mild Infection

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    According to a large study from Israel published in The BMJ, most symptoms or conditions that arise following a mild case of COVID-19 tend to persist for several months, but typically return to normal within a year.

    Specifically, the study found that individuals who have been vaccinated are at a reduced risk of developing breathing difficulties, the most prevalent effect to occur following a mild case of COVID-19, compared to those who have not been vaccinated.

    These findings suggest that, although the long covid phenomenon has been feared and discussed since the beginning of the pandemic, the vast majority of mild disease cases do not suffer serious or chronic long-term illness, say the researchers.

    Long covid is defined as symptoms persisting or new symptoms appearing more than four weeks after initial infection. In March 2022, an estimated 1.5 million people in the UK (2.4% of the population) reported long covid symptoms, mainly fatigue, shortness of breath, loss of smell, loss of taste, and difficulty concentrating.

    But the clinical effects of long covid one year after mild infection and their association with age, sex, covid-19 variants, and vaccination status are still unclear.

    To address this, researchers compared the health of uninfected individuals with those who had recovered from mild covid-19 for a year after infection.

    They used electronic records of a large public healthcare organization in Israel, in which almost 2 million members were tested for covid-19 between 1 March 2020 and 1 October 2021. Over 70 long covid conditions were analyzed in a group of infected and matched uninfected members (average age 25 years; 51% female).

    They compared conditions in unvaccinated people, with and without covid-19 infection, controlling for age, sex, and covid-19 variants, during early (30-180 days) and late (180-360 days) time periods after infection. Conditions in vaccinated versus unvaccinated people with covid-19 were also compared over the same time periods.

    To ensure only mild disease was assessed, they excluded patients admitted to hospitals with more serious illnesses. Other potentially influential factors, such as alcohol intake, smoking status, socioeconomic level, and a range of pre-existing chronic conditions were also taken into account.

    Covid-19 infection was significantly associated with increased risks of several conditions including loss of smell and taste, concentration and memory impairment, breathing difficulties, weakness, palpitations, streptococcal tonsillitis, and dizziness in both early and late time periods, while hair loss, chest pain, cough, muscle aches and pains and respiratory disorders resolved in the late period.

    For example, compared with non-infected people, mild covid-19 infection was associated with a 4.5-fold higher risk of smell and taste loss (an additional 20 people per 10,000) in the early period and an almost 3-fold higher risk (11 per 10,000 people) in the late period.

    The overall burden of conditions after infection across the 12-month study period was highest for weakness (an additional 136 people per 10,000) and breathing difficulties (107 per 10,000).

    When conditions were assessed by age, breathing difficulties were the most common, appearing in five of the six age groups but remaining persistent throughout the first year post-infection in the 19-40, 41-60, and over 60 years age groups.

    Weakness appeared in four of the six age groups and remained persistent in the late phase only in the 19-40 and 41-60 age groups.

    Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings were similar across the wild-type, Alpha, and Delta covid-19 variants.

    Vaccinated people who became infected had a lower risk of breathing difficulties and similar risk for other conditions compared with unvaccinated infected patients.

    The researchers point to some limitations, such as incomplete measurement within medical records, so data might not fully reflect diagnoses and outcomes reported. And they can’t rule out the possibility that covid-19 patients may use healthcare services more frequently, resulting in higher reporting and increased screening for potential covid-related outcomes in these patients.

    Nevertheless, this was a large detailed analysis of health records across a diverse population, representing one of the longest follow-up studies in patients with mild covid-19 to date. And findings should apply to similar western populations worldwide.

    “Our study suggests that mild covid-19 patients are at risk for a small number of health outcomes and most of them are resolved within a year from diagnosis,” say the researchers.

    “Importantly, the risk for lingering dyspnoea was reduced in vaccinated patients with breakthrough infection compared with unvaccinated people, while risks of all other outcomes were comparable,” they add.

    Reference: “Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study” by Barak Mizrahi, Tamar Sudry, Natalie Flaks-Manov, Yoav Yehezkelli, Nir Kalkstein, Pinchas Akiva, Anat Ekka-Zohar,  Shirley Shapiro Ben David, Uri Lerner, Maytal Bivas-Benita and Shira Greenfeld, 11 January 2023, The BMJ.
    DOI: 10.1136/bmj-2022-072529

    BMJ

    Microbiology

    Maternal Tdap vaccination protects youngest infants from pertussis

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    Introduction of a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination during pregnancy can protect the youngest infants from pertussis, according to a study published online Feb. 6 in JAMA Pediatrics.

    Tami H. Skoff, from the U.S. Centers for Disease Control and Prevention in Atlanta, and colleagues calculated and compared incidence rates in the pre-maternal Tdap vaccination period (2000 to 2010) and the post-maternal Tdap vaccination period (2012 to 2019) for younger than 2 months (target group of maternal vaccination) and infants age 6 to less than 12 months (comparison group).

    The researchers found that in the pre-maternal Tdap vaccination period, annual pertussis incidence did not change among infants aged younger than 2 months and increased slightly among older infants, with no change in the difference in incidence seen between the two age groups. In the post-maternal Tdap vaccination period, there was a decrease in incidence observed among infants younger than 2 months (slope, −14.53 per 100,000 infants per year), while no change was seen for older infants (slope, 1.42 per 100,000 infants per year). During the post-maternal Tdap vaccination period, the incidence rate difference between the two age groups decreased significantly (slope, −14.43 per 100,000 infants per year). Between the pre- and post-maternal Tdap vaccination periods, pertussis incidence rate differences were significantly different (slope difference, −14.51 per 100,000 infants per year).

    “Our suggest that maternal Tdap vaccination is associated with a reduction in disease burden among the youngest and most vulnerable age group (

    More information:
    Tami H. Skoff et al, US Infant Pertussis Incidence Trends Before and After Implementation of the Maternal Tetanus, Diphtheria, and Pertussis Vaccine, JAMA Pediatrics (2023). DOI: 10.1001/jamapediatrics.2022.5689

    Science X Network

    Microbiology

    COVID-19 vaccine protection lasts at least six months after second dose, finds study

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    Vaccine protection against severe outcomes from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) lasts at least six months after the second dose, but protection is lower for older patients, according to a study published online Feb. 3 in JAMA Network Open.

    Yuchen Wei, Ph.D., from the Chinese University of Hong Kong, and colleagues examined the change in against hospitalization and mortality due to the omicron variant in a case-control study involving adults with SARS-CoV-2 infection who died or were hospitalized from Jan. 1 to June 5, 2022 (32,823 case participants) and propensity score-matched adults with SARS-CoV-2 omicron (131,328 control participants).

    The researchers found that for at least six months after the second dose of both the CoronaVac and BNT162b2 vaccines, vaccine effectiveness against death or hospitalization was maintained (74.0 and 77.4 percent, respectively). In those aged 18 to 49 years, vaccine effectiveness against death was 86.4 and 92.9 percent for those receiving two doses of CoronaVac and BNT162b2, respectively, while for patients aged 80 years and older, vaccine effectiveness decreased to 61.4 and 52.7 percent, respectively. At four to six months after the third dose, overall vaccine effectiveness against death was >90 percent for CoronaVac, BNT162b2, and the mixed vaccine schedule.

    “A booster dose is recommended for older individuals to restore immunity,” the authors write. “This is especially critical in a setting like Hong Kong, where coverage of the of the vaccine is still insufficient among older residents.”

    One author disclosed financial ties to Beth Bioinformatics.

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    More information:
    Yuchen Wei et al, Estimation of Vaccine Effectiveness of CoronaVac and BNT162b2 Against Severe Outcomes Over Time Among Patients With SARS-CoV-2 Omicron, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2022.54777

    Journal information:
    JAMA Network Open

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    Microbiology

    Study reveals three or four doses of mRNA vaccines remain effective in preventing omicron infection

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    An international research team has provided one of the first real-world estimates of vaccine effectiveness against omicron infections, irrespective of symptoms or severity. From a serological survey of 5,310 blood donors and other volunteers, the researchers estimated that three doses of the Comirnaty or CoronaVac vaccines were, respectively, 48% or 30% effective in preventing omicron infection shortly after vaccination, further improving shortly after a fourth dose.

    The researchers expected protection from also relates to protection from transmission, and this is one of the first reports suggesting vaccine-induced protection from virus transmission. However, vaccine effectiveness waned rapidly thereafter over 100 days. Moreover, the researchers estimated that more than 45% of the Hong Kong population was infected between 1 January and 31 July 2022. These findings have been published in Nature Medicine.

    The SARS-CoV-2 omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. Between 1 January to 31 July 2022, Hong Kong experienced an unprecedented fifth wave of COVID-19 infections driven predominantly by the omicron BA.2 subvariant. As local COVID transmission before 2022 was minimal, population immunity to SARS-CoV-2 in Hong Kong was almost entirely vaccine-derived at the start of the wave.

    There is extensive data on how COVID-19 vaccines robustly prevent severe disease, hospitalization and death. However, few studies have investigated their effectiveness in preventing omicron infections, irrespective of symptoms or severity. Prevention of infection itself indicates prevention of both asymptomatic and symptomatic disease transmission.

    Combining results from a community-wide serological survey of 5,310 and volunteers with SARS-CoV-2 viral load data from city-wide wastewater surveillance, the researchers estimated, (i) vaccine effectiveness against all omicron BA.2 infections conferred by two, three and four homologous doses of the Comirnaty or CoronaVac vaccines for 100 days after each dose and (ii) COVID-19 infection attack rate in Hong Kong from 1 January to 31 July 2022. The researchers developed two in-house ELISA assays detecting IgG antibodies to the nucleocapsid (N) or Open Reading Frame 8 (ORF8) protein of SARS-CoV-2, with the latter assay developed specifically to detect past infection in CoronaVac vaccines.

    The researchers estimated three and four doses of Comirnaty were 48% and 69% effective in preventing omicron infection, respectively, seven days after vaccination, waning to 26% and 35% by 100 days after vaccination. Three and four doses of CoronaVac were 30% and 56% effective after seven days respectively, declining to 6% and 11% by 100 days.

    Meanwhile, the researchers identified that more than 45% of the in Hong Kong was infected by SARS-CoV-2 between 1 January and 31 July 2022 (i.e., an infection attack rate of 45%). Accordingly, official case counts, incorporating both Reverse Transcriptase-PCR (RT-PCR) testing and Rapid Antigen Testing (RAT) results, identified less than 41% of all infections.

    The results indicate that booster vaccination using either the mRNA or inactivated vaccine platforms is effective in preventing SARS-CoV-2 omicron BA.2 infection in the short-term. This adds to previous studies demonstrating robust effectiveness in preventing severe disease and death.

    Thus, surge booster campaigns, particularly with updated bivalent mRNA vaccines, could be strategically used to rapidly boost population immunity when there is risk of future waves of infections arising from a concerning novel virus variant. The comparatively lower infection attack rate in Hong Kong by July 2022, versus various overseas jurisdictions, highlights the effect of supplementing vaccination campaigns with continued and social measures (e.g., masking) on reducing disease transmission.

    More information:
    Jonathan J. Lau et al, Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population, Nature Medicine (2023). DOI: 10.1038/s41591-023-02219-5

    Journal information:
    Nature Medicine

    The University of Hong Kong

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