A new commentary by infectious disease experts published in Annals of Internal Medicine says that, for patient safety, masking should continue in health care settings. This message, from authors at George Washington University School of Medicine and the National Institutes of Health (NIH), conflicts with a recent commentary from authors from 8 US institutions suggesting that the time for universal masking is over.
Masking has been a controversial mitigation strategy during the COVID pandemic because high-quality evidence of efficacy is lacking and because the topic has become highly politicised. Regardless, real-world experience demonstrates the effectiveness of mask-wearing in clinical settings where data shows that transmission from patient-to-staff and staff-to-patent, when both are masked, is uncommon. Since health care personnel report being driven to show up for work even when they are ill themselves, the argument in support of mask-wearing becomes even more compelling.
Those without symptoms may also transmit respiratory viruses, particularly SARS-CoV-2. While the Omicron strain has been milder, infection could still cause severe or life-threatening disease or prolonged illness if transmitted to at-risk patients, such as the elderly or immunocompromised. With the still-looming risks, now does not seem the time to take off masks in the health care setting. Instead, the authors advocate strongly for continued mask use for infection prevention.
With the administration of the first COVID vaccines two years ago, public health officials found an increase in cases of myocarditis, particularly among young males who had been vaccinated with mRNA vaccines. The underlying cause of these reactions remained a mystery.
Now Yale scientists have identified the immune signature of these heart inflammation cases. Published in the journal Science Immunology, their findings eliminate some of the theorised causes of the heart inflammation and point to the consequences of a slightly over-stimulated immune system.
Myocarditis is a generally mild inflammation of heart tissue which can cause scarring but is usually resolved within days. The increased incidence of myocarditis during vaccination was seen primarily in males in their teens or early 20s, who had been vaccinated with mRNA vaccines, which are designed to elicit immune responses specifically to the SARS-CoV-2 virus.
According to the Centers for Disease Control and Prevention (CDC), among males aged 12 to 17, about 22 to 36 per 100 000 experienced myocarditis within 21 days after receiving a second vaccine dose. The incidence of myocarditis was 50.1 to 64.9 cases per 100 000 after infection with the COVID virus among males in this age group.
For the new study, the Yale research team conducted a detailed analysis of immune system responses in those rare cases of myocarditis among vaccinated individuals. They found that the heart inflammation was not caused by antibodies created by the vaccine, but rather by a more generalised response involving immune cells and inflammation.
“The immune systems of these individuals get a little too revved up and over-produce cytokine and cellular responses,” said team leader Carrie Lucas, associate professor of immunobiology.
Earlier research had suggested that increasing the time between vaccination shots from four to eight weeks may reduce risk of developing myocarditis.
Lucas noted that, according to CDC findings, the risk of myocarditis is significantly greater in unvaccinated individuals who contract COVID than in the vaccinated. She emphasised that vaccination offers the best protection from COVID-related disease.
“I hope this new knowledge will enable further optimising mRNA vaccines, which, in addition to offering clear health benefits during the pandemic, have a tremendous potential to save lives across numerous future applications,” said Anis Barmada, an MD/PhD student at Yale School of Medicine, who is a co-first author of the paper with Jon Klein, also a Yale MD/PhD student.
According to new research from the Universities of Cambridge and Edinburgh, COVID vaccination protection in people with severe obesity wanes faster than in people of normal weight. The study suggests that people with obesity are likely to need more frequent booster doses to maintain their immunity.
Previous studies on COVID vaccines have suggested that antibody levels may be lower in vaccinated people who have obesity and that they may remain at higher risk of severe disease than vaccinated people with normal weight. The reasons for this have, however, remained unclear.
This study, published in the journal Nature Medicine, shows that the ability of antibodies to neutralise the virus (their ‘neutralisation capacity’) declines faster in vaccinated people who have obesity. The findings have important implications for vaccine prioritisation policies around the world.
During the pandemic, people with obesity were more likely to be hospitalised, require ventilators and to die from COVID. In this study, supported by the NIHR Bioresource and funded by UKRI, the researchers set out to investigate how far two of the most extensively used vaccines protect people with obesity compared to those with a normal weight, over time.
A team from the University of Edinburgh looked at real-time data tracking the health of 3.5 million people in the Scottish population as part of the EAVE II study. They looked at hospitalisation and mortality from COVID in adults who received two doses of COVID vaccine (either Pfizer-BioNTech or AstraZeneca).
They found that people with severe obesity (a BMI > 40kg/m2) had a 76% higher risk of severe COVID outcomes, compared to those with a normal BMI. A modest increase in risk was also seen in people with obesity (30-39.9kg/m2), which affects a quarter of the UK population, and those who were underweight. ‘Break-through infections’ after the second vaccine dose also led to hospitalisation and death sooner (from 10 weeks) among people with severe obesity, and among people with obesity (after 15 weeks), than among individuals with normal weight (after 20 weeks).
University of Edinburg leader Prof Sir Aziz Sheikh said: “Our findings demonstrate that protection gained through COVID vaccination drops off faster for people with severe obesity than those with a normal body mass index. Using large-scale data assets such as the EAVE II Platform in Scotland have enabled us to generate important and timely insights that enable improvements to the delivery of COVID vaccine schedules in a post-pandemic UK.”
The University of Cambridge team studied people with severe obesity attending the Obesity clinic at Addenbrooke’s Hospital in Cambridge, and compared the number and function of immune cells in their blood to those of people of normal weight.
They studied people six months after their second vaccine dose and then looked at the response to a third ‘booster’ vaccine dose over time. The Cambridge researchers found that six months after a second vaccine dose, people with severe obesity had similar levels of antibodies to the COVID virus as those with a normal weight – but those antibodies were less effecctive.
The antibodies’ neutralisation capacity was reduced in 55% of individuals with severe obesity were found to have unquantifiable or undetectable ‘neutralising capacity’ compared to 12% of people with normal BMI.
“This study further emphasises that obesity alters the vaccine response and also impacts on the risk of infection,” said first author Dr Agatha van der Klaauw. “We urgently need to understand how to restore immune function and minimise these health risks.”
The researchers found that antibodies produced by people with severe obesity were less effective at neutralising the SARS-CoV-2 virus, potentially because the antibodies were not able to bind to the virus with the same strength.
When given a third (booster) dose of a COVID vaccine, neutralisation capacity was restored in both the normal weight and severely obese groups. But the researchers found that immunity again declined more rapidly in people with severe obesity, putting them at greater risk of infection with time.
Results from a Swedish study of nearly three million women and girls published by The BMJ found that there was no evidence of an increased risk of post-COVID vaccination menstrual changes that were significant enough for healthcare interaction.
The researchers found only weak and inconsistent associations were found between COVID vaccination and contact with healthcare for postmenopausal bleeding. These were even less consistent for menstrual disturbance and premenstrual bleeding.
These findings do not provide any substantial support for a causal association between COVID vaccination and diagnoses related to menstrual or bleeding disorders, say the researchers.
Many women have reported changes to their periods after a COVID vaccination, such as the number of days they bleed and the heaviness of the flow. Self-reporting may capture events that normally would not result in a healthcare contact but may still be sufficiently disturbing to be relevant for the affected women. But calculating the strength of a potential association based on self reports can be unreliable.
To address this, researchers in Sweden drew on high quality health registry data to evaluate the risks of menstrual disturbance and bleeding after COVID vaccination in 2 946 448 women and girls aged 12-74 years from December 2020 to February 2022.
Contact with healthcare included primary care visits, specialist outpatient visits, and days of hospital stay related to menstrual disturbance or bleeding before or after menopause.
Risks were assessed by vaccine (Pfizer-BioNTech, Moderna, or Oxford-AstraZeneca) and dose (unvaccinated and first, second, and third dose) over two time windows (1-7 days, considered the control period, and 8-90 days).
In the main analysis, more than 2.5 million (88%) of women received at least one covid-19 vaccination and over 1.6 million (64%) of vaccinated women received three doses during the study period.
The highest risks for bleeding in postmenopausal women were seen after the third dose in the 1-7 days risk window (28%) and in the 8-90 days risk window (25%).
Adjusting for socioeconomic factors, previous healthcare use, and for several specific medical conditions had only a modest effect on these results.
Analyses of individual vaccines and risk of postmenopausal bleeding suggested a 23-33% increased risk after 8-90 days with Pfizer-BioNTech, and Moderna after the third dose, but a less clear association with Oxford-AstraZeneca.
In premenopausal women, weak associations were found for menstrual disturbance or bleeding after vaccination with any dose (13% or 8% after 1-7 days and 6% or 1% after 8-90 days, respectively). However, adjusting for other factors almost completely removed these weak associations, suggesting that a causal effect is unlikely.
These are observational findings and the authors point to several limitations, including the fact that the time between onset, start of symptoms, and date of healthcare contact might be considerable, making the interpretation of effect of different risk windows challenging.
But this was a large study with near complete follow-up, using mandatory data from nationwide registers.
As such, they say: “We observed weak and inconsistent associations between SARS-CoV-2 vaccination and healthcare contacts for postmenopausal bleeding, and even less consistent for menstrual disturbance, and premenstrual bleeding.”
They add: “These findings do not provide any substantial support for a causal association between SARS-CoV-2 vaccination and healthcare contacts related to menstrual or bleeding disorders.”
The World Health Organization has announced that it was downgrading COVID from its previous status as a public health emergency of international concern, but noted that the pandemic is still not over. Recent spikes have occurred in Southeast Asia and the Middle East, and the agency warns that thousands of people a day are still dying from the virus. It also made a number of recommendations for national healthcare systems to maintain the gains made against the virus and for pandemic preparedness.
The WHO’s International Health Regulations (2005) (IHR) Emergency Committee had been following the decline in hospital and ICU missions along with the growth of immunity, and decided in its meeting on Thursday 4 May that it was time to recommend a transition to long-term management.
“It’s with great hope that I declare COVID-19 over as a global health emergency,” WHO Director-General Tedros Adhanom Ghebreyesus said, concurring the Committee’s advice.
“That does not mean COVID-19 is over as a global health threat,” he said, adding he wouldn’t hesitate to reconvene experts to reassess the situation should COVID-19 “put our world in peril.”
He also expressed concern that even though infections were down, COVID-19 surveillance was falling.
While various governments had been transitioning down for a while, this marks a major step for the WHO. The virus killed millions and sent the global economy into a nosedive, plunging millions more into poverty and reversing many decades of socioeconomic development.
While COVID was no longer considered to be an ongoing global threat, the WHO made number of recommendations for countries:
Sustain the national capacity gains and prepare for future events.
Integrate COVID-19 vaccination into life course vaccination programmes.
Bring together information from diverse respiratory pathogen surveillance data sources to allow for a comprehensive situational awareness.
Prepare for medical countermeasures to be authourisedwithin national regulatory frameworks to ensure long-term availability and supply.
Continue to work with communities and their leaders to achieve strong, resilient, and inclusive risk communications and community engagement (RCCE) and infodemic management programmes.
Continue to lift COVID-19 international travel related health measures
Secondary bacterial pneumonia was extremely common in patients with COVID-19, affecting almost half the patients who required support from mechanical ventilation. In a study published in the Journal of Clinical Investigation, researchers applied machine learning to medical record data and found that secondary bacterial pneumonia that does not resolve was a key driver of death in COVID patients.
Bacterial infections may even exceed death rates from the viral infection itself, according to the findings. The study’s researchers at Northwestern University Feinberg School of Medicine also found evidence that COVID does not cause a “cytokine storm,” so often believed to cause death.
“Our study highlights the importance of preventing, looking for and aggressively treating secondary bacterial pneumonia in critically ill patients with severe pneumonia, including those with COVID-19,” said senior author Benjamin Singer, MD, professor at Northwestern.
The investigators found nearly half of COVID patients develop a secondary ventilator-associated bacterial pneumonia.
“Those who were cured of their secondary pneumonia were likely to live, while those whose pneumonia did not resolve were more likely to die,” Singer said. “Our data suggested that the mortality related to the virus itself is relatively low, but other things that happen during the ICU stay, like secondary bacterial pneumonia, offset that.”
“The term ‘cytokine storm’ means an overwhelming inflammation that drives organ failure in your lungs, your kidneys, your brain and other organs,” Singer said. “If that were true, if cytokine storm were underlying the long length of stay we see in patients with COVID-19, we would expect to see frequent transitions to states that are characterised by multi-organ failure. That’s not what we saw.”
The study analysed 585 patients in the intensive care unit (ICU) at Northwestern Memorial Hospital with severe pneumonia and respiratory failure, 190 of whom had COVID. The scientists developed a new machine learning approach called CarpeDiem, which groups similar ICU patient-days into clinical states based on electronic health record data. This novel approach, which is based on the concept of daily rounds by the ICU team, allowed them to ask how complications like bacterial pneumonia impacted the course of the illness.
These patients or their surrogates consented to enrol in the Successful Clinical Response to Pneumonia Therapy (SCRIPT) study, an observational trial to identify new biomarkers and therapies for patients with severe pneumonia. As part of SCRIPT, an expert panel of ICU physicians used state-of-the-art analysis of lung samples collected as part of clinical care to diagnose and adjudicate the outcomes of secondary pneumonia events.
“The application of machine learning and artificial intelligence to clinical data can be used to develop better ways to treat diseases like COVID and to assist ICU physicians managing these patients,” said study co-first author Catherine Gao, MD.
“The importance of bacterial superinfection of the lung as a contributor to death in patients with COVID-19 has been underappreciated, because most centres have not looked for it or only look at outcomes in terms of presence or absence of bacterial superinfection, not whether treatment is successful or not,” said study co-author Richard Wunderink, MD.
The next step in the research will be to use molecular data from the study samples and integrate it with machine learning approaches to understand why some patients go on to be cured of pneumonia and some don’t. Investigators also want to expand the technique to larger datasets and use the model to make predictions that can be brought back to the bedside to improve the care of critically ill patients.
While masking was a critical preventative measure to protect healthcare workers, patients and visitors during the COVID pandemic, infectious disease researchers argue against masking, saying that that as the pandemic dies down, the routine use of masking should be reconsidered. Previous policies over healthcare masking use against SARS-CoV-2 transmission were formulated against a background which assumed no population immunity and no countermeasures.
In editorial published in Annals of Internal Medicine, the authors argue for the discontinuation of universal COVID masking in healthcare settings as infection rates and mortality have fallen and access to testing and therapeutics is widespread, as is immunity. Universal masking is therefore no longer of benefit and its own drawbacks, such as facial irritation and hindering communication, are more of a hinderance.
In addition to difficulties faced by speakers of different languages as well as the hard of hearing, masks have a number of detrimental effects for communication. “The increase in listening effort required when masks are used in clinical encounters is associated with increased cognitive load for patients and clinicians,” the authors wrote. In addition to making clinicians’ jobs harder, they also impact the all-important clinician–patient relationship, as face masks “obscure facial expression; contribute to feelings of isolation; and negatively impact human connection, trust, and perception of empathy.”
Healthcare workers should instead adopt an approach for SARS-CoV-2 similar to that of any other endemic respiratory disease. Drawing on the experience of the COVID pandemic, they suggest a more flexible, responsive approach to masking policies. In response to future epidemics or localised outbreaks “may justify more widespread or targeted masking policies, respectively, as part of a bundled response. High-quality epidemiologic data with frequent updates and regular reevaluation are needed to inform scale-up or scale-down decisions.”
The South African Health Products Regulatory Authority (SAHPRA) issued media statements on 4 August 2022 and 12 September 2022, relating to two fatal cases of Guillain-Barré syndrome (GBS) following vaccination with COVID-19 Vaccine Janssen. SAHPRA has been informed of a third fatal case of GBS following vaccination with the same vaccine.
A causality assessment of the reported case was conducted by the National Immunisation Safety Expert Committee (NISEC) using the World Health Organization’s (WHO) methodology. Following investigations, the case was classified as a vaccine product-related event. The events reported in the vaccine recipient were consistent with the case definition of GBS and no other likely cause of GBS was identified at the time of illness.
As previously communicated, GBS is a very rare but potentially severe neurological adverse event that is associated with the administration of various vaccines and other medicines and can also be triggered by some bacterial or viral infections, including SARS-CoV-2. Symptoms of GBS range from mild to severe, and may include muscle weakness, muscle pain, numbness, and tingling. In many cases, GBS resolves with no serious after-effects, but in some cases GBS can cause serious or life-threatening problems.
Regulatory authorities have previously investigated reports of GBS associated with COVID-19 vaccines. They concluded that COVID-19 Vaccine Janssen may increase the risk of GBS. GBS is therefore listed as a rare adverse event in the professional information (PI) for COVID-19 Vaccine Janssen.
Investigations and causality assessment of all reported severe adverse events following immunisation (AEFI) with all COVID-19 vaccines are ongoing. The outcomes of these investigations and causality assessments will be shared with the public as soon as they are completed.
Important points to note
COVID-19 vaccines have consistently been shown to prevent severe forms of disease, hospitalisation and death. Based on the currently available evidence, SAHPRA has determined that the benefits of COVID- 19 vaccination far outweigh the very low risk of severe adverse events, including GBS. The public are strongly advised not to delay COVID-19 vaccination if eligible in terms of the national vaccination programme.
SAHPRA urges the public to report any suspected adverse events following the use of all medicines and vaccines. Reporting can be done at a health facility or by downloading the Med Safety App (https://medsafety.sahpra.org.za/), which is available for Android and iOS phones, or by calling the COVID-19 hotline at 0800 029 999. More information regarding AEFIs reported for the COVID-19 vaccines and how to report an AEFI is available from the SAHPRA website: https://aefi-reporting.sahpra.org.za/.
More information regarding AEFIs reported for the COVID-19 vaccines and how to report an AEFI is available from the SAHPRA website: https://aefi-reporting.sahpra.org.za/.
The World Health Organization (WHO) announced that it has updated its tracking system and working definitions for variants of SARS-CoV-2, to better reflect the current global variant landscape, to independently evaluate Omicron sublineages in circulation, and classify new variants more clearly when required.
Omicron variants now accounts for 98% of circulating SARS-CoV-2, and new variants will likely emerge from this genetic background. Based on its latest risk assessment [PDF], South Africa has reported a strong increase in XBB.1.5 from 1% in December 2022, to 10% in January 2023, and 76% as of the latest report from February 2023.
Based on comparisons of antigenic cross reactivity using animal sera, replication studies in experimental models of the human respiratory tract, and evidence from clinical and epidemiological studies in humans, WHO experts conclude that, compared to previous variants, Omicron represents the most divergent variant of concern (VOC) seen so far. Since its emergence, Omicron viruses have continued to evolve genetically and antigenically with an expanding range of sublineages, which so far have had all been characterised by evasion of existing population immunity and a preference to infect the upper respiratory tract (versus lower respiratory tract), as compared to pre-Omicron VOCs.
The previous system classified all Omicron sublineages as part of the Omicron VOC and was not detailed enough to compare new descendent lineages with altered phenotypes to the Omicron parent lineages (BA.1, BA.2, BA.4/BA.5). So, WHO variant tracking system will consider the classification of Omicron sublineages independently as variants under monitoring (VUMs), variants of interest (VOIs), or VOCs.
WHO is also updating the working definitions for VOCs and VOIs. The main update consists in making the VOC definition more specific, to include major SARS-CoV-2 evolutionary steps that require major public health interventions.
In addition, going forward, WHO will assign Greek labels for VOCs, and will no longer do so for VOIs.
With these changes factored in, Alpha, Beta, Gamma, Delta as well as the Omicron parent lineage (B.1.1.529) are considered previously circulating VOCs. WHO has now classified XBB.1.5 as a VOI.
WHO emphasizes that these changes do not imply that the circulation of Omicron viruses no longer pose a threat to public health. Rather, the changes have been made in order to better identify additional or new threats over and above those posed by the current Omicron viruses in circulation.
Early in the COVID pandemic, it became clear that children infected with the coronavirus rarely developed serious disease. One hypothesis has been that children already have some immunity provided by memory T cells generated by common colds. Researchers at Karolinska Institutet are now able to show that OC43, one of the coronaviruses that cause common colds, boosts the immune response to COVID. The study, which is published in PNAS, could give rise to more tailored vaccine programmes for children and adults.
After studying unique blood samples from children taken before the pandemic, Karolinska Institutet researchers have now identified memory T cells that react to cells infected with SARS-CoV-2.
This new study reinforces this hypothesis and shows that T cells previously activated by the OC43 virus can cross-react against SARS-CoV-2.
Four coronaviruses cause common colds
One of the four coronaviruses causing seasonal common cold symptoms could stimulate an immune response with T cells able to also react to cells infected with SARS-CoV-2.
“These reactions are especially strong early in life and grow much weaker as we get older,” says the study’s corresponding author Annika Karlsson, research group leader at the Department of Laboratory Medicine, Karolinska Institutet. “Our findings show how the T-cell response develops and changes over time and can guide the future monitoring and development of vaccines.”
Strong immunity at the age of two
The results indicate that the memory T-cell response to coronaviruses develops as early as the age of two. The study was based on 48 blood samples from two- and six-year-old children, and 94 samples from adults between the ages of 26 and 83. The analysis also included blood samples from 58 people who had recently recovered from COVID-19.
“Next, we’d like to do analogous studies of younger and older children, teenagers and young adults to better track how the immune response to coronaviruses develops from childhood to adulthood,” says Marion Humbert, postdoctoral researcher currently at the Department of Medicine Huddinge, Karolinska Institutet, joint first author with Anna Olofsson, doctoral student at the Department of Laboratory Medicine.
