“Patients taking fluvoxamine reported steadily improving fatigue and quality-of-life scores over 60 to 90 days, with fewer side effects than those on placebo, they said.

The findings were published on March 30,2026 in Annals of Internal Medicine.

The investigators enrolled 399 adults with fatigue persisting 90 or more days following a confirmed SARS-CoV-2 infection.

The trial was conducted in 22 outpatient medical sites in Brazil between October 2023 and February 2025.

The subjects were randomized to 60-day treatment with fluvoxamine (100 mg twice daily), metformin (750 mg twice daily) or matching placebo.

The study excluded people with diabetes, stroke, Lyme disease or other COVID-19 complications. It also excluded people identified as substance abusers, those with uncontrolled psychiatric conditions and those already being treated with fluvoxamine or metformin.

The primary outcome was the change between baseline and 60-day scores on the Fatigue Severity Scale (FSS), a 9-item self-reported measure of fatigue severity, with higher scores indicating worse fatigue.

The investigators reported that, at day 60, fluvoxamine subjects had achieved a significant reduction in fatigue compared with placebo subjects. And the effect was sustained at day 90.

Fluvoxamine treatment also improved quality-of-life scores, while metformin treatment showed no such benefit.

They reported that adverse events were less frequent with fluvoxamine (20.0%) than with metformin (28.8%) or placebo (29.7%).

The authors concluded, “This study supports the potential benefit of fluvoxamine in people with long COVID and fatigue lasting at least 90 days after acute COVID-19.”

In a large, randomized trial, researchers at Mass General Brigham have found that high-dose vitamin D3 did not reduce COVID-19 infection severity, but may impact long COVID outcomes. Results of the study are published in The Journal of Nutrition.

“There’s been tremendous interest in whether vitamin D supplements can be of benefit in COVID, and this is one of the largest and most rigorous randomized trials on the subject,” said senior author JoAnn Manson, MD, DrPH, of the Mass General Brigham Department of Medicine. “While we didn’t find that high-dose vitamin D reduced COVID severity or hospitalizations, we observed a promising signal for long COVID that merits additional research.”

Vitamin D has been hypothesized to boost immune health, but clinical evidence in the context of COVID-19 has been mixed. The Vitamin D for COVID-19 (VIVID) Trial aimed to provide clarity by rigorously evaluating high-dose vitamin D3 supplementation among newly diagnosed COVID-19 patients and their household contacts. Across the United States and Mongolia, 1,747 adults who had recently tested positive for COVID-19 and 277 household contacts were randomized to receive either daily vitamin D3 (9,600 IU/day for two days followed by 3,200 IU/day) or daily placebo for four weeks. The U.S. trial was conducted from December 2020 to September 2022 while the Mongolia trial ran from September 2021 to April 2022. The median time between the participants’ positive COVID-19 tests and the initiation of vitamin D supplementation or placebo was three days.

Alongside Manson, lead authors Davaasambuu Ganmaa, Kaitlyn Cook and team used stratified randomization and statistical weighting to ensure factors that can affect COVID-19 outcomes (including age, sex, body mass index, race/ethnicity and COVID-19 vaccination status) were balanced between the two groups.

The rate of healthcare utilization (including hospitalizations, in-person or virtual clinic visits, and emergency visits) or death did not differ between the vitamin D and placebo groups over a four-week period. Similarly, no significant differences were found in symptom severity. Taking high-dose vitamin D also didn’t reduce the rate at which household contacts contracted COVID-19.

However, an analysis of the participants who adhered to the vitamin D regimen demonstrated a signal that they were less likely to experience long COVID symptoms at eight weeks than those who took placebo pills. In the vitamin D group, 21% reported at least one persistent symptom, compared to 25% in the placebo group, a difference of borderline statistical significance.

“Long COVID, which can include symptoms of fatigue, shortness of breath, brain fog, other cognitive challenges and more, continues to significantly impact people’s lives,” said Manson. “We hope to conduct further research in larger populations on whether long-term vitamin D supplementation reduces the risks and severity of long COVID.”

Authorship: In addition to Manson and Ganmaa, Mass General Brigham authors include Allison Clar, Michael Rueschman, Aditi Hazra, Howard D. Sesso, Valerie E. Stone, Patricia Copeland and Georgina Friedenberg. Additional authors include Cook, Polyna Khudyakov, Dorjbal Enkhjargal, Tsolmon Bilegtsaikhan, Kenneth H. Mayer, Raji Balasubramanian, Douglas C. Smith, Quanhong Lei, Todd Lee, Emily G. McDonald, Tserenkhuu Enkhtsetseg, Erdenebaatar Sumiya, Yansanjav Narankhuu, Myagmarsuren Erdenetuya, Dalkh Tserendagva, Rikard Landberg, Niclas Roxhed and Susanne Rautiainen.

Disclosures: Roxhed is a founder and shareholder of Capitainer AB, a company commercializing the blood collection devices used in this study. All other authors declare no conflicts of interests.

Funding: The study received anonymous foundation support and philanthropic support from Jon Sabes of Minneapolis, Minn. The authors also acknowledge support from the Tishcon Corporation, which donated the vitamin D and placebo study capsules; Takeda; and Capitainer cards. The authors have not declared a specific grant for this research from any funding agency in the public, commercial or nonprofit sectors.

Paper cited: Ganmaa, D., et al. “A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The VIVID Trial.” The Journal of Nutrition. DOI: 10.1016/j.tjnut.2026.101398

Vaccination against COVID-19 and influenza are recommended during pregnancy by the World Health Organization (WHO) and Norway, as pregnant women and their newborns have an increased risk of severe outcomes from these diseases. For at-risk groups, the WHO recommends a vaccination target of 75% for both infections.

These findings emphasise the need for more targeted strategies and better integration of vaccinations into routine pre-natal care for pregnant women in Norway, along with comprehensive surveillance of maternal vaccination.

In Norway, the influenza vaccine is provided during the influenza season, while the COVID-19 vaccine is available year-round. Generally, both vaccines are recommended to pregnant women during the second and third trimester. Pregnant women in Norway access these vaccines through self-initiated appointments with healthcare professionals; the influenza vaccine is provided at a cost, while the COVID-19 vaccine is free.

Significant variation in coverage depending on month of delivery and timing during pregnancy

Stecher et al. looked at how many pregnant women received the influenza and COVID-19 vaccines during the 2023/24 influenza season, at what stage of pregnancy they received the vaccine, and whether uptake differed by age group or region.

A total of 53,161 women were included in the study. Researchers drew data from two Norwegian national registries, with the study population comprising all women who delivered in Norway between 1 October 2023 and 30 September 2024, as identified in the Medical Birth Registry Norway (MBRN). The records and birth data from MBRN were then linked to data from the Norwegian Immunisation Registry (SYSVAK).

Despite universal recommendations for vaccination during pregnancy, coverage in the influenza season 2023/24 was low at 29.9% and 12.1% for influenza and COVID-19, respectively, while only 11.4% of pregnant women received both vaccines.

For the influenza vaccine, 22.3% of women were vaccinated in the second or third trimester. Coverage increased from 16.4% in October to 26.4% in November, and levelled off thereafter. It was highest among women delivering in February at 50.8%, declining afterwards. Coverage for the COVID-19 vaccine followed a similar pattern to influenza, with 10.1% of women receiving the vaccine in the second or third trimester.

Low vaccination rates despite high trust in health authorities

There were considerable differences across regions and age groups, despite the population’s high level of trust in health authorities and recommendations, and the authors point to practical and psychological barriers to vaccination. The lowest uptake was among women aged 25 years or younger. Regionally, the Oslo and Vestland counties had the highest vaccination coverage, while the lowest coverage was found in Northern Norway.

Stecher et al. suggest removing financial barriers, improving accessibility, and exploring information sources on vaccines trusted by women to address hesitancy. The authors also cite international evidence supporting the integration of free vaccination into routine pre-natal care, with vaccination coverage for whooping cough among pregnant women improving when the vaccine was introduced into Norway’s maternal immunisation programme.

Similar challenges globally, including limited surveillance systems and inconsistent integration, highlight the importance of coordinated efforts to promote maternal immunisation in Europe and worldwide.

The drugs are effective but don’t eliminate the virus; HIV remains hidden in “reservoirs” throughout the body, ready to reactivate if treatment stops.

But researchers at Case Western Reserve University, in collaboration with the University of Pittsburgh, have made a significant breakthrough in HIV treatment. They’ve shown that NK (Natural Killer) cells—specialized immune cells that naturally target virus-infected and tumor cells—can be enhanced to better fight HIV infections.

Their findings were recently published in mBio, the scientific journal for the American Society of Microbiology.

“NK cell immunotherapy is already being used for cancer therapy, and the data from those studies provides a great foundation for translation of this approach to an HIV cure strategy,” said Mary Ann Checkley-Luttge, a senior research associate at the Case Western Reserve School of Medicine, who led the study. “We are hoping that NK cell immunotherapy can help reduce the reservoir enough to allow long-term immunological control of HIV without ART.”

Checkley-Luttge works in the lab of Jonathan Karn, a professor at the School of Medicine and pioneer in HIV research as director of the Case Center for AIDS Research.

The research team discovered that NK cells taken from HIV-positive patients can be expanded and enhanced in the lab to more effectively target and reduce these viral reservoirs.

This discovery marks a significant step toward long-term HIV remission by enhancing the body’s immune system. The approach could enable people with HIV to control the virus without lifelong dependence on daily antiretroviral medications.

The groundwork for such a discovery was supported by Case Western Reserve’s long-standing interdisciplinary collaboration and robust HIV research infrastructure. The School of Medicine houses a National Institutes of Health-designated Center for AIDS Research founded more than 30 years ago, and the Center for Excellence on the Impact of Substance Use on HIV, providing access to cutting-edge technologies essential for high-impact HIV research.

“Our team’s next goals are to test whether lab-enhanced NK cells can work as ‘off-the-shelf’ therapy,” said Karn, Distinguished University Professor and chair of the Department of Molecular Biology and Microbiology. “We plan to conduct studies using advanced animal models that closely mimic HIV infection in humans and then work toward clinical trials in the next two years to test this approach in people living with HIV.”

The research was made possible through blood donations from people living with HIV and represents a collaborative effort between patients, researchers and institutions working toward better HIV treatments.

The findings were published Feb. 9, 2026 in The Lancet.

The study’s lead author, Professor Mika Kivimaki (University College London – Faculty of Brain Sciences), said, “Obesity is well known as a risk factor for metabolic syndrome, diabetes, cardiovascular disease, and many other chronic conditions. Here we have found robust evidence that obesity is also linked to worse outcomes from infectious diseases, as becoming very ill from an infection is markedly more common among people with obesity.”

The new analysis included pooled data on 67,766 adults from two Finnish studies and 479,498 from the UK Biobank. The average age at baseline was 42 years old for the Finnish cohorts and 57 years old for the UK Biobank cohort.

Participants had their body mass index (BMI) assessed when they entered the studies (1998–2002 in the Finnish studies; 2006–10 in UK Biobank), and they were subsequently tracked for an average of 13-14 years.

They were followed through national hospitalization and mortality registries for hospital admission and death due to infectious disease. At baseline, the subjects had no recent history of infection related hospitalization.

For BMI, they were classed as having healthy weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²) or obesity — class I obesity (30.0–34.9 kg/m²) class II (35.0–39.9 kg/m²) or class III (≥40.0 kg/m²).

During follow-up, there were 8,230 infection cases in the Finnish cohorts and 81, 945 in UK Biobank cohort.

The investigators reported that subjects with obesity, defined as BMI ≥30 kg/m², had a 70% higher risk of hospitalization or death from any infectious disease compared to those with a BMI between 18.5 to 24.9.

Notably, subjects with the most severe obesity (BMI ≥40 kg/m²) had three times the risk of death from infection compared to those with a healthy weight.

Author Dr Solja Nyberg, University of Helsinki (Finland), says “Our findings suggests that people living with obesity are significantly more likely to become severely ill or to die from a wide range of infectious diseases. As obesity rates are expected to rise globally, so will the number of deaths and hospitalizations from infectious diseases linked to obesity.”

Kivimäki added, “Our finding that obesity is a risk factor for a wide range of infectious diseases suggests that broad biological mechanisms may be involved. It is plausible that obesity weakens the immune system’s ability to defend against the infectious bacteria, viruses, parasites or fungi, therefore resulting in more serious diseases. Evidence from trials of GLP-1 weight-loss drugs fits with this, as reducing obesity also appears to lower the risk of severe infections, alongside many other health benefits. That said, additional research is required to confirm the mechanisms underlying these associations.”

“This is important given the rise in vaccine hesitancy, which has resulted in a downward trend in flu vaccination that coincided with a high rate of hospitalization this flu season,” said the study’s lead author, Shivan Mehta, MD, MBA, MSHP, associate chief innovation officer at Penn Medicine. “Many nudge interventions directed to patients only on vaccinations have shown limited effectiveness in the United States, so we wanted to make sure that we addressed both sides of the exam room: the patient and the clinician.”

The researchers believe these results might point to some strategies that could help boost how many people get the shot every year for an illness that has hospitalized up to 710,000 people each year since 2010—and killed as many as 52,000 Americans annually.

Nudging versus standard care 

The study tested several forms of “nudging,” a behavioral science concept that means small tweaks that make the healthiest choices the easiest ones. Patients who were eligible for the vaccine received flu shot reminder texts (or automated voice recordings), had automatic orders for a flu shot waiting for their clinician to approve, and monthly personalized messages were sent to providers that compared their patients’ vaccination rates to their clinician peers.

More than 52,000 people were randomly assigned to two groups: one that received all of the nudges or a “standard care” control group at either the University of Pennsylvania Health System or the University of Washington’s health system, UW Medicine The standard care team didn’t get any of the nudges and followed the usual path for getting a flu vaccine, which relies largely on the clinician remembering to offer the vaccine based on information in the electronic health records. Researchers found that almost 3,000 more people got flu shots when they were nudged than would have been expected if they got normal care.

Why nudging patients and clinicians worked 

Mehta and his colleagues are encouraged by their findings, driven mainly by the importance of communication and trust.

“We think the automatic order encouraged primary care physicians to have a conversation with their patients, and we know these clinicians still have a lot of trust from their communities,” said co-senior author Amol Navathe, MD, PhD, a professor of Medical Ethics and Health Policy, as well as a professor of Health Care Management in the Wharton School.

The work continues at scale 

The team has replicated their work at Lancaster General Health in the University of Pennsylvania Health System, which serves a rural and suburban patient base that looks somewhat different than the study populations in this study drawn largely from Philadelphia and Seattle. They are still analyzing the results of this replication study.

Since the work leverages existing tools in the electronic health record along with other available technologies but no additional staffing or human effort, it could be particularly attractive to health systems looking to augment their flu shot efforts.

“Future interventions could be more successful by complementing the automated communication with clinical staff to engage with patients that are still hesitant, and integrating flu vaccine nudges with other interventions focused on preventive health, like cancer screening,” Mehta said.

Q: How would you summarize your study for a lay audience?

Although adolescents and young adults comprise only one quarter of the sexually active population in the United States, approximately half of new sexually transmitted infections (STIs) are diagnosed in people of these ages. Compared to older adults, little is known about how teens and young adults access and use services like STI screening and treatment, sexual health vaccinations and HIV pre-exposure prophylaxis (PrEP). PrEP is a preventive medicine for people who do not have HIV but are at increased risk of exposure.

Our study examined how people of different ages and genders used sexual health services in a Boston-based clinic that provides free, comprehensive services across six hospital- and community-based sites. While our study focused on a single metropolitan area, our findings reflect broader national challenges in sexual health service utilization.

Q: What question were you investigating?

We set out to learn whether adolescents and young adults who interacted with the Massachusetts General Hospital Sexual Health Clinic utilized sexual health services differently than older adults. We also aimed to identify opportunities to increase patient engagement and deliver existing services more consistently and equitably to those who need them most.

Q: What methods or approach did you use?

We analyzed data from 7,949 visits to the Sexual Health Clinic, made by 4,004 individuals, between January 2019 to June 2021. We grouped data on visits, STI diagnoses, PrEP use and health insurance by age and gender. We then used statistical analysis to examine how outcomes—such as being prescribed preventive PrEP—were associated with factors like age and gender.

Q: What did you find?

We found that among patients at increased risk for HIV exposure, PrEP prescribing differed by age and gender. For example, cisgender males who were 26 years old or under with PrEP indications were prescribed the medicine at slightly higher rates (86%) than their counterparts over age 26 (83%). However, among cisgender females at increased risk, only 20% of those at or under age 26 were prescribed PrEP compared to 72% of those over age 26.

Looking at the data from another angle, we discovered that young cisgender females (at or under age 26) were 63% less likely to be prescribed PrEP during their visits than young cisgender males. Additionally, only 17% of visits attended by even younger cisgender females (under age 22) who were candidates for PrEP received it.

Q: What are the implications?

Addressing disparities by age, gender and race/ethnicity in HIV prevention—via PrEP prescriptions—is critical. Significant gaps for young cisgender females with PrEP indications reflect opportunities for improved programming tailored to this population, with the potential to avert new HIV diagnoses.

Gaps between PrEP need and prescription may also reflect patient preferences or other barriers such as the need for quarterly visits for oral PrEP or anticipated costs. They could also reflect provider-related barriers, such as limited knowledge of the drug or failure to consider PrEP for individuals other than men who have sex with men. Policy efforts focused on alleviating these barriers may help reduce HIV incidence by improving how well PrEP reaches those who would benefit from it.

Q: What are the next steps?

Future work should explore why PrEP prescription rates among young cisgender females are much lower than their counterparts, as well as evaluate targeted interventions to improve PrEP access for indicated young women.

Authorship: In addition to Neilan and Ard, Mass General Brigham authors include Yiqi Qian, Grace Chamberlin, Scott E. Hadland, Madhava Narasimhadevara, Vandana Madhavan and Fatma M. Shebl.

Paper cited: Neilan, A., et al. “Differences in Sexual Health Clinic Services by Age and Gender in Metropolitan Boston.” Sexually Transmitted Diseases. DOI: 10.1097/OLQ.0000000000002275

Funding: This work was supported by the Morton N. Swartz Transformative Scholar Award in Infectious Diseases, the Claflin Distinguished Scholars Award and the Eunice Kennedy Shriver National Institute for Child Health and Human Development (K08 HD094638-S).

Disclosures: None.

“This is the first time in their lives these adolescents could formally stop taking daily oral medications for HIV treatment and just get two injections every eight weeks,” said first and corresponding author on one study and co-senior author on the other, Aditya Gaur, MD, St. Jude Department of Infectious Diseases, who co-leads the IMPAACT 2017 study, also referred to as the More Options for Children and Adolescents (MOCHA) study. “After one year, this treatment approach appears safe and is tolerated by and acceptable to adolescents.”

All injectable treatment regimen is safe

Adolescents with HIV currently take daily oral medications to keep the virus in check. However, taking daily medications, for any chronic disease is not easy and many struggle with medication adherence. Maintaining consistent medication adherence can be challenging, especially for adolescents, underscoring the need for long-lasting injectables.

The published companion papers describing the IMPAACT 2017/MOCHA study constitute the longest and largest described multinational experience to date of this first all-injectable HIV treatment regimen in a diverse group of virologically-suppressed adolescents. Results show that after 48 weeks, there were no safety concerns, and viral loads remained suppressed.

“We observed no unexpected safety signals from the first-ever all-injectable combination retroviral regimen in this adolescent population,” Gaur said. “We saw the expected concentrations of each drug known to be effective in adults and continued virological control.”

When long-acting injectable antiviral medications emerged as an alternative to daily oral medications, it was a major milestone for prevention and treatment of HIV. This new report from the IMPAACT 2017/MOCHA study assessed the safety, antiviral activity and pharmacokinetics of the first all-injectable HIV treatment regimen of cabotegravir and rilpivirine given intramuscularly once every two months in adolescents with HIV from around the world. This treatment regimen was already approved for adolescents with HIV who are 12 years or older weighing 35 kilograms or more by the US Food and Drug Administration and a growing number of other regulatory agencies from around the world based on prior clinical findings from the IMPAACT 2017/MOCHA study, which the companion papers further support.

Finding out what type of treatment adolescents want

Learning that the all-injectable antiviral HIV treatment regimen is safe for patients is important, however, the therapy will only be effective if patients are willing to take it. Therefore, led by Elizabeth Lowenthal based at Children’s Hospital of Philadelphia, the researchers assessed how well patients accepted and tolerated the injectable medications. At 48 weeks, 100% of participants reported they would rather get the injectable regimen than the oral medications. In addition, of the 144 participants originally enrolled in the study, the majority (140) continued the treatment through the reported 48-week period, indicating a high level of acceptability.

“It is very exciting to enter an era of long-acting medications for HIV,” Gaur said. “Thanks to the contributions of the study participants, their families, site staff, study team and the collaboration between the NIH, ViiV Healthcare and Johnson & Johnson who made this study possible, we can now offer patients more options, such as these injectables, which provide freedom from daily medications and can be tailored based on patients’ preferences.”

For more information about the study, please see ClinicalTrials.gov using the identifier NCT03497676.

Authors and funding

The authors of the injectable-only safety study are Kristin Baltrusaitis, St. Jude; Edmund Capparelli and Brookie Best, University of California San Diego; John Moye, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Dwight Yin and Ellen Townley, National Institute of Allergy and Infectious Diseases; Gaerolwe Masheto, Botswana Harvard Health Partnership; Sarah Buisson and Rachel Scheckter, FHI 360; Conn Harrington, ViiV Healthcare; Mark Marzinke, Johns Hopkins University School of Medicine; Elizabeth Lowenthal, Children’s Hospital of Philadelphia; Andi Ace and Kyle Whitson, Frontier Science Foundation; Shawn Ward and Ryan Milligan, Frontier Science Foundation; Jenny Huang, Amy Cheung and Gilly Roberts, GlaxoSmithKline; Thomas Kakuda and Eileen Birmingham, Johnson & Johnson; Sisinyana Mathiba, University of Witwatersrand; Linda Aurpibul, Chiang Mai University; Violet Korutaro, Baylor College of Medicine Children’s Foundation Uganda; Christiana Smith, University of Colorado School of Medicine; Faeezah Patel, University of Witwatersrand; Evette Moodley, CAPRISA; and Carolyn Bolton Moore, Centre for Infectious Disease Research in Zambia.

The study was supported by funding from ViiV Healthcare and Johnson & Johnson.

The other authors of the preference study include first and corresponding author Elizabeth Lowenthal, Children’s Hospital of Philadelphia. The study’s other co-senior author is Carolyn Bolton-Moore, Centre for Infectious Disease Research in Zambia/University of Alabama Birmingham. Additional authors include Jennifer Chapman, Chermiqua Tsosie and Martina Vaca, The Children’s Hospital of Philadelphia; Kaleb Branch, University of Pennsylvania Perelman School of Medicine; Kristin Baltrusaitis and Grace Kovic, Harvard T.H. Chan School of Public Health; Sanjna Merchant, University of Pennsylvania College of Arts and Sciences; Barbara Heckman and Andi Ace, Frontier Science Foundation; Rodica Van Solingen-Ristea, Johnson & Johnson; Conn Harrington and Irina Kolobova, Viiv Healthcare; Dwight Yin and Ellen Townley, National Institute of Allergy and Infectious Diseases; Michael Whitton and Sarah Buisson, FHI 360 IMPAACT Operations Center; Allison Agwu, Johns Hopkins University School of Medicine; Christiana Smith, University of Colorado School of Medicine; Mary Paul, Baylor College of Medicine; Avy Violari, University of Witwatersrand; Evette Moodley, Centre for the AIDS Programme of Research in South Africa; Maxensia Owor, MU-JHU Care Limited; Kulkanya Chokephaibulkit, Mahidol University; Samantha Fry, FAMCRU; Jennifer Jao, Northwestern University Feinberg School of Medicine and Charles Mitchell, University of Miami Miller School of Medicine.

The study was supported by grants from the National Institutes of Health (UM1AI068632, UM1AI068616, UM1AI106716 and HHSN275201800001I) and ViiV Healthcare Inc.

Image: First and corresponding author on one study and co-senior author on the other, Aditya Gaur, MD, St. Jude Department of Infectious Diseases, who co-leads the IMPAACT 2017 study, also referred to as the More Options for Children and Adolescents (MOCHA) study.

View more Credit: Courtesy of St. Jude Children’s Research Hospital

The study, led by researchers from Imperial College London, found that of the participants initially hesitant about getting a COVID-19 vaccine, 65% went on to get vaccinated at least once.

The findings offer a novel perspective on the main types of vaccine hesitancy during the COVID-19 pandemic. Their potential to be reversed may help inform the targeting and messaging for future roll-outs of novel vaccines.

While vaccine hesitancy is not a new phenomenon, with WHO naming vaccine hesitancy as one of the top 10 global health threats in 2019 [1], reduced uptake of various vaccines including childhood vaccinations against measles and pertussis (whooping cough), remains a major public health concern.

COVID-19 vaccination roll-out began in the UK on 8^th December 2020, with a phased strategy that prioritised vaccines on the basis of age and clinical need. “We wanted to look at COVID-19 vaccine hesitancy in more depth to identify groups with more persistent forms of hesitancy and their main concerns. Understanding these drivers is critical to address vaccine uptake and better control disease spreads,” explained lead author Professor Marc Chadeau-Hyam from Imperial College London, UK.

Researchers analysed longitudinal survey data from 1.1 million adults (aged 18 and older, 57% female) from the Real-time Assessment of Community Transmission (REACT) Study (at the time of the initial COVID-19 vaccine roll-out between January 2021 and March 2022). They compared vaccine attitudes at enrolment with subsequent vaccination uptake from National Health Service (NHS) vaccination records up to May 7, 2024, to identify categories and drivers of vaccine hesitancy.

During the pandemic, participants were asked whether they had been or intended to get vaccinated. Those who refused the vaccine, or were sceptical about vaccination, were asked about their reasons for hesitancy from a checklist of 23 options as well as a free text option [2].

Vaccine effectiveness and health effects key reasons for hesitancy

Overall, 3.3% (37,982 of 1.1 million) of participants reported some degree of COVID-19 vaccine hesitancy and subsequent vaccination data was available through NHS records linkage for 24,229 (64%) of them. Hesitancy rates declined over time from an initial high of 8% of those surveyed in January 2021, to a low of 1.1% at the start of 2022. There was a small uptick in hesitancy to over 2.2% in February and March 2022 during the Omicron wave (see figure 1 in paper).

The researchers identified eight categories of vaccine hesitancy including concerns about effectiveness and side-effects, perception of low risk from COVID-19 and mistrust of vaccine developers, and fear of vaccines and reactions [3]. Among the hesitant who provided a reason for hesitancy, 41% (12,498 of 30,701) reported concerns around long-term health effects, 39% (11,953) that they wanted to wait to see whether the vaccine worked, and 37% (11,287) that they had concerns about side effects.

Reasons for hesitancy varied across demographic groups with, for example, men more likely than women to report not feeling COVID-19 was a personal risk (18% vs 10%); women more likely to be worried about fertility-related consequences (21% vs 8%), while those aged 74 years or older were more likely to be against vaccines in general compared with 18-24 year olds (12% vs 2.5%).

The analysis of subsequent vaccination behaviour found that the likelihood of remaining unvaccinated was higher for older people, women, people of Black ethnicity, people who were unemployed or living in deprived areas, those with a history of COVID-19, and people with a lower level of education.

Majority of vaccine hesitant individuals got vaccinated

People who reported the most common reasons for hesitancy (i.e., those related to vaccine efficacy or health concerns), were most likely to change their mind and subsequently get vaccinated against COVID-19 (see figure 6 in paper).

In contrast, people expressing hesitancy relating to lack of trust, perception of low personal risk, and general anti-vaccine sentiment were two to three-times less likely to get vaccinated compared to those who did not report these reasons.

“We show that certain types of vaccine hesitancy are more readily addressed than others, for example concerns relating to pregnancy or breastfeeding,” said co-author Professor Helen Ward from Imperial College London and the National Institute for Health and Care Research Imperial Biomedical Research Centre, UK. “Our study suggests that as the vaccine was rolled out, public confidence increased and the original vaccine scepticism was largely overcome.”

According to co-author Professor Paul Elliott from Imperial College London, “What we learned from the COVID-19 experience is the importance of ensuring that people have access to reliable and trusted information so they can make well-informed decisions about their personal health choices. Reliable, easy-to-understand information, for example, on vaccine effectiveness and potential risks, is of particular importance in the case of a public health emergency such as COVID-19, which involved the rapid deployment at-scale of new vaccine technologies.”

The authors acknowledge some limitations of the study, including that NHS vaccine records and self-reported vaccine status showed some inconsistencies, likely reflecting both imperfect recall and imperfect coverage in the NHS data. Additionally, vaccine hesitant respondents were less likely to consent to NHS record linkage, potentially introducing selection bias, which may limit the generalisability of the findings.

Writing in a linked Comment, Professor Silvio Tafuri from the University of Bari Aldo Moro, Bari, Italy (who was not involved with the study) underscored the “valuable contribution” of the study and concluded, “whereas these data reflect the extraordinary setting of SARS-CoV-2 vaccination, it is crucial to ascertain whether similar drivers of hesitancy affect ordinary (ie, routine or seasonal) vaccinations, in order to guide context-specific public health interventions at the micro, meso, and macro levels.”

A Cornell psychology professor argues in new research that scholars of rational decision-making and many public health professionals have misunderstood how people make such decisions: based less on raw facts than intuition about them, and how that “gist” aligns with their core values.

In a pair of studies testing competing theories, two general questions that elicited participants’ overall sense of risks and benefits explained vaccine hesitancy significantly better than the more precise, quantitative measures long favored by economists and psychologists. Categorizations of risks and benefits simply as none, low, medium or high significantly predicted whether people intended to get a vaccine or not. Study participants who perceived benefits as none or low, or risks as medium or high, tended to not vaccinate, for example.

“We make decisions based on the bottom-line gist of information: What does all this information boil down to? What’s the decision really about?” said Valerie Reyna, the Lois and Melvin Tukman Professor of Human Development in the Department of Psychology and College of Human Ecology. “If we know the essence of how someone feels about these ideas, we can explain and predict their intentions with respect to vaccination.”

Reyna, director of the Lab for Rational Decision Making, is the first author of “A New Look at Vaccination Behaviors and Intentions: The Case of Influenza,” published Nov. 29 in Behavioral Sciences.

Classic decision theories – with names like “reasoned action” and “planned behavior” – emphasize tradeoffs between good or bad outcomes and their probabilities, assuming that rational mechanisms explain and predict behavior. Newer “dual process” theories contrast impulsive and deliberative systems, suggesting people make better decisions when engaging the latter.

“All of these modern models essentially augment that core idea of a rational person making a decision about vaccination,” Reyna said. “Somehow, that doesn’t seem to describe the current context we’re in for most people.”

As a developer of “fuzzy trace” theory, Reyna proposes that two key processes drive decision-making: encoding of literal facts, and creation of meaning about those facts based on one’s background and experiences.

The new research asked more than 700 college students and nearly 200 community members whether they had received a flu vaccine in the past year or intended to get one (substantial numbers in both samples were unvaccinated). Participants answered questions relevant to classic, dual process and fuzzy trace theories, including about their knowledge of and access to flu vaccines; their precise perception of risk on a scale from zero to 100; and their overall sense of the vaccine’s risks and benefits.

Among the younger adults, vaccine knowledge and accessibility explained only 14% of the variation in intentions to get flu vaccines. That total jumped to 58% when considering responses to the gist questions. In the community sample, similarly, gist questions improved the ability to predict vaccination intentions from 57% to 80%.

“Part of our mind looks at details and precise facts, but the other part of our mind looks at the bottom-line, qualitative gist – and that’s the more determinative part,” Reyna said.  “People form a global impression of what they are told and experience, for example, ‘Overall, I think the benefits from vaccination are high and the risks are nil.’ That would be a gist for people who get vaccinated, and that’s what we showed.”

The research suggests opportunities to reduce vaccine hesitancy through sustained communication that incorporates gist principles, in contrast to prevailing approaches that rely on lists of facts and trust in experts. Sharing basic background knowledge – such as the difference between viruses and bacteria, or how vaccines naturally enlist immune systems – is essential but not sufficient, Reyna said. Facts must be put into context to enable a conceptual, gist understanding. Then practitioners must explain how vaccine risks and benefits map onto core values – a desire to keep family and neighbors safe, for example, or to make free and informed choices.

“If you follow that recipe, you will be much more likely to make a difference with people, according to our research,” Reyna said. “You have to take the right approach, and it’s fundamentally different from what we’re currently doing.”

The research received support from the National Institute of Standards and Technology; the U.S. Department of Agriculture; and the Institute for Trustworthy AI and Society, where Reyna is a lead faculty member.

The study was published on Dec. 22, 2025 in Annals of Internal Medicine.

The investigators compared once-weekly ISL+LEN  to a daily oral bictegravir, emtricitabine, and tenofovir alafenamide combination (B/F/TAF) in subjects with HIV-1 infection.

Outcomes included rates of virologic suppression through week 48 and adverse events.

Investigators in the phase 2, open-label trial enrolled 104 subjects (USA) who had achieved an HIV-1 RNA viral load of less than 50 copies/mL while receiving daily B/F/TAF for at least 24 weeks.

The researchers randomized the subjects (102 in each cohort) to receive either once-weekly ISL (2 mg) plus LEN (300 mg) or daily B/F/TAF. The trial lasted for 48 weeks.

They reported that, at week 24, one ISL+LEN subject and no B/F/TAF subjects had an HIV-1 RNA viral load of 50 copies/mL or more, a difference of 1.9%.

At week 48, 94.2% and 92.3% of ISL+LEN and B/F/TAF subjects, respectively, achieved an HIV-1 RNA viral load of less than 50 copies/mL, a difference of 1.9%. There were no subjects in either group with an HIV-1 RNA viral load of 50 copies/mL or more.

Two ISL+LEN subjects discontinued treatment (before week 24) due to adverse events that were not related to the drug they used in the study.

The authors concluded, “Once-weekly oral ISL-plus-LEN maintained high rates of virologic suppression through week 48 and was not associated with any treatment-related grade 3 or greater or serious AEs… Once-weekly oral islatravir plus lenacapavir (ISL+LEN) has the potential to address adherence challenges with daily HIV-1 treatment.”

The guideline is published on World AIDS Day, December 1, 2025, to raise awareness of new approaches to prevention.

Pre-exposure prophylaxis involves an HIV-negative person starting antiretroviral medications before potential HIV exposures occur in order to prevent infection. Postexposure prophylaxis involves taking 28 days of antiretrovirals right after a potential exposure to HIV.

“Canada is not at all on track to achieve its goal of eliminating HIV as a public health threat by 2030. Our aim with this guideline is to support front-line health care providers, policy-makers, community members, and others in expanding the use of these safe and effective tools for preventing HIV,” says Dr. Darrell Tan, lead author and infectious disease physician at St. Michael’s Hospital, Toronto, Ontario. “A wide array of PrEP and PEP options now exists in Canada. We need to urgently expand their use until all people have equitable access to prevention strategies that they find suitable.”

HIV infections in Canada are concentrated in specific populations, with 38% of new infections in gay, bisexual, and other men having sex with men (GBM); 25% in people who inject drugs (PWID); and 4% in GBM-PWID. More than one-third of infections occur in females. Some Indigenous communities are particularly heavily affected, with more cases in Saskatchewan and Manitoba than the national average.

The guideline, an update to 2017 guidance, was developed through the Canadian Institutes of Health Research (CIHR) Pan-Canadian Network for HIV and STBBI (sexually transmitted and blood-borne infections) Clinical Trials Research (CTN+). It includes easy reference tables with recommendations on medication regimens, indications, monitoring, and more.

Key differences from the 2017 guideline include the “explicit inclusion of self-identified need as a reason for PrEP initiation” and the expanding range of available PrEP choices, with newer regimens including an injection given every 2 months.

The authors’ aim is to support clinical decision-making in primary care, infectious diseases, emergency medicine, sexual health, nursing, pharmacy, and related disciplines, as well as community workers who promote PrEP and PEP.

“Because lack of PrEP and PEP awareness among key populations and clinicians is a common barrier to implementation, public health officials, professional societies, and other trusted authorities should play leadership roles in promoting these strategies in collaboration with community organizations and tracking uptake in conjunction with HIV surveillance data,” the authors write. “Information should be framed in a positive light to counteract the stigma and apprehension that sometimes surround PrEP and PEP.”