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Advances in medicine are continuously emerging, challenging all members of the interprofessional team to remain aware of important updates and how they may improve clinical practice. This is particularly true for the prevention and treatment of infectious diseases. However, increasing demands on the time and resources of healthcare practitioners make it difficult to stay up-to-date on the latest clinical research and guidelines, as well as the implications for patient care. This article highlights recent advances in our understanding of infectious diseases and strategies to prevent and treat these illnesses.

CAN WEARING AN N95 MASK CAUSE CARDIOPULMONARY OVERLOAD?

Following the outbreak of COVID-19, the use of face masks is considered essential to decreasing the risk of viral transmission.^[1] N95 respirators are a type of mask that are used to protect the face from particles or liquid. They form a close seal around the nose and mouth, and efficiently filtrate airborne particles.^[2] In countries around the world, the use of face masks has become commonplace in everyday life; however the adverse effects associated with this practice are unconfirmed.^[3]

In a new study, Chinese researchers investigated the impact of extended N95 respiratory use in daily life. They conclude that wearing an N95 mask for a prolonged period could affect physiologic and biochemical parameters. The authors report that the effect was primarily initiated by increased respiratory resistance and subsequent decreased blood oxygen and pH, which contributed to sympathoadrenal system activation and epinephrine as well as norepinephrine secretion elevation, and a compensatory increase in heart rate and blood pressure.^[3]

"Although healthy individuals can compensate for this cardiopulmonary overload, other populations, such as elderly individuals, children, and those with cardiopulmonary diseases, may experience compromised compensation," they write. The study is reported in a Research Letter to JAMA Network Open published online June 9.^[3]

The authors, led by Riqiang Bao, MD, Shanghai Jiaotong University School of Medicine, note that in China, mask use remains a highly adopted practice in everyday life, and the N95 mask offers the highest level of protection against viruses. They say that studies to date on the adverse effects of wearing masks have yielded inconsistent conclusions because of the short duration of intervention.^[3]

They conducted the current randomized crossover trial, which took place in a metabolic chamber, to control daily calorie intake and physical activity levels of the participants. The 30 healthy volunteers (mean age 26 years) were randomly assigned to receive interventions with and without the N95 mask for 14 hours, during which they exercised for 30 minutes in the morning and afternoon using an ergometer at 40% (light intensity) and 20% (very light intensity) of their maximum oxygen consumption levels. Venous blood samples were taken before and after the intervention for blood gas and metabolite analysis.^[3]

Results showed that wearing the N95 mask resulted in reduced respiration rate and oxygen saturation by pulse oximetry (SpO₂) within 1 hour, with elevated heart rate (mean change, 3.8 beats/min) 2 hours later until the mask was taken off. The authors report that during the light-intensity exercise, mask-induced cardiopulmonary stress was further increased, as heart rate (mean change, 7.8 beats/min) and blood pressure increased (mean change: 6.1 mm Hg systolic and 5.0 mm Hg diastolic) and respiration rate (mean change, −4.3 breaths/min) and SpO₂ (mean change, −0.66%) decreased. Energy expenditure (mean change, 0.5 kJ) and fat oxidation (mean change, 0.01 g/min) were elevated.^[3]

After the 14-hour masked intervention, venous blood pH decreased, and calculated arterial pH showed a decreasing trend. Metanephrine and normetanephrine levels were increased. Participants also reported increased overall discomfort with the N95 mask.^[3]

In their discussion, the researchers note that: "Chronic cardiopulmonary stress may also increase cardiovascular diseases and overall mortality." They acknowledge though that the study was limited to only 30 young healthy participants in a laboratory setting, and further investigation is needed to explore the effects of different masks on various populations in clinical settings.^[3]

Methodology Questioned

However, US researcher Erik Van Iterson, PhD, who conducted a previous study that did not find any clinically meaningful physiologic effects of wearing an N95 mask,^[4] is not impressed by the findings of the new study, saying it does not add any reliable information to the overall body of literature on the subject. Van Iterson also questioned the soundness of the methodology.

"My take-home message is that if you want to wear an N95 mask, there is little evidence to suggest that the mask will have a negative effect on your cardiovascular health or function while doing activities of daily living," Van Iterson, director of cardiac rehabilitation and metabolic exercise stress testing at the Cleveland Clinic, Cleveland, Ohio told theheart.org | Medscape Cardiology. "This study does nothing to suggest otherwise," he said. "If anything, this communication is somewhat detrimental because it is pointing to a narrative that isn't there, in that it suggests these masks may be harmful when there really is no evidence for that."  

Van Iterson pointed out that the researchers were measuring physiologic function with indirect techniques, including wearable technology, which he said had not been validated for use in these dynamic conditions. "And it's not completely clear how the oxygen saturation was measured. It is challenging to directly measure gas exchange when people are wearing an N95 mask," he added.

Van Iterson also took issue with the authors' interpretation of the data. "It is very challenging to interpret this data. The authors are suggesting that there are clinically relevant differences. But the quality of the data itself is not reliable, and what they are interpreting as clinically relevant differences is also rather generous," he commented. 

He gives the example of oxygen saturation level, which is reported as a mean change of 0.66%. "They are reporting that as a statistically significant difference but that is not a clinically meaningful difference.  A 0.66% difference is well within the measurement error of the technology. And [it] could easily be attributable to just plain noise," he noted. "Overall, the changes they found, even if they are valid, are not enough to be clinically meaningful," he added.

Van Iterson also pointed out that the study was conducted in healthy young people, and what differences would be found in different populations was "pure speculation. I certainly do not believe that this evidence would support the idea that wearing an N95 mask would cause negative effects on cardiovascular function," he concluded. 

In their own previous study of exercise testing in healthy individuals wearing masks, "We found that when performing light-to-moderate-intensity exercise there really is no issue in wearing an N95 mask or a cloth style mask in terms of physiological function," he noted. "However, with maximal intensity exercise levels there becomes a substantial subjective effect of wearing a face covering on perceived exertion, and there is a small change in physiological function in that respiration rates are increased and there is some reduction in oxygen saturation levels. But these changes did not meet physiological thresholds that would warrant termination of the tests because of those changes, and they were not considered clinically significant," he added.

Also commenting on the study, Michael Campos, MD, University of Miami Miller School of Medicine, Florida, pointed out that N95 masks are only now generally worn by healthcare providers in an ICU setting and only for short periods of time. Campos and colleagues conducted a previous study,^[5] showing the more widely used surgical masks to be safe for healthy people and for people with chronic obstructive pulmonary disease. "I guess the clinical impact of this new study is very limited," he said.

MILLIONS WHO HAD COVID-19 STILL DON'T HAVE SENSE OF SMELL, TASTE

Millions of Americans who were infected with COVID-19 still have not fully recovered their sense of taste or smell, a new report says.^[6] Smell and taste disorders tend to appear early in the disease course and occur more frequently in SARS-CoV-2 infection compared with other respiratory disorders.^[7]

Almost 36 million people were diagnosed in 2021, and 60% of them reported accompanying losses in smell or taste, says the study by Mass Eye and Ear, which is affiliated with Harvard Medical School, in Boston. The study was published in The Laryngoscope.^[6]

Most people fully regained the senses, but about 24% did not get smell back completely, and more than 3% had no recovery, the study says. The report says the numbers were similar with those who lost the sense of taste.

Researchers looked at the records of 30,000 adults who had COVID-19 in 2021. They reported that patients who suffered more severe cases were less likely to regain some or all their senses.

Some patients said they lost appetite because they couldn't smell food. There is concern, too, about losing the ability to smell gas and smoke, spoiled food, and dirty diapers.

PATIENTS WITH POST-COVID COGNITIVE SYMPTOMS MAY HAVE GLIOSIS

Following COVID-19, some patients experience depressive symptoms with or without cognitive symptoms (COVID-DC), which can continue for long periods of time. A new case-control study aimed to determine whether gliosis is present in patients experiencing these persistent symptoms. Investigators measured translocator protein distribution volume (TSPO VT), a marker of gliosis, using positron emission tomography (PET).^[8] Gliosis is a common term that refers to a reaction of the central nervous system to injury of the brain or spinal cord. Of 40 patients who were treated at a tertiary care psychiatric hospital in Canada, the level of TSPO VT was 9.23 mL/cm³ among patients with COVID-DC and 7.72 mL/cm³ among control persons, indicating that patients with persistent COVID-DC may have gliosis and inflammation. Differences were particularly notable in the ventral striatum and dorsal putamen.

"Most theories assume there is inflammation in the brain [with] long COVID," but that assumption had not been studied, author Jeffrey H. Meyer, MD, PhD, Canada Research Chair in Neurochemistry of Major Depressive Disorder at the University of Toronto, told Medscape Medical News. "Such information is pivotal to developing treatments."

The study was published online May 31 in JAMA Psychiatry.^[8]

Quantifiable Marker

The investigators sought to determine whether levels of TSPO VT, which are quantifiable with PET, are elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of patients with COVID-DC, compared with patients without this syndrome. These brain regions were chosen, according to the authors, "because injury in these regions, which can cause gliosis, also induces symptoms of COVID-DC."^[8]

The study was conducted from April 2021 through June 30, 2022. The investigators compared levels of TSPO VT in the selected brain regions of 20 participants with COVID-DC (mean age, 32.7 years; 60% women) with that of 20 control persons (mean age, 33.3 years; 55% women). TSPO VT was measured with fluorine F18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET.^[8]

The difference in TSPO VT was most noticeable in the ventral striatum (mean difference, 1.97 mL/cm³) and dorsal putamen (mean difference, 1.70 mL/cm³). The study authors suggest that gliosis in these areas may explain some of the persistent symptoms reported in structured clinical interviews and assessed on neuropsychological and psychological testing.^[8]

For patients with COVID-DC, motor speed on the finger-tapping test was negatively associated with dorsal putamen TSPO VT (r, −0.53). The 10 participants with COVID-DC whose speed was lowest had higher mean dorsal putamen TSPO VT levels than control persons by 2.3 mL/cm³.^[8]

The investigators could not assess a possible association between the ventral striatum TSPO VT and anhedonia because all participants had these symptoms. No significant correlations were found between depression and TSPO VT in the prefrontal cortex or anterior cingulate cortex. The authors acknowledge that the study was cross-sectional, and so the duration of persistently elevated TSPO VT is not yet known. In addition, elevation in TSPO VT is not completely specific to glial cells, and although correlations with finger-tapping test performance reflect associations between brain changes and symptoms, they do not prove cause and effect.^[8]

"Presently, clinicians can use treatments for symptoms in other illnesses that are [also] common with long COVID. We need better than this," said Meyer. "Clients with long COVID should be able to state their symptoms, and the practitioner should have an evidence-based matching treatment to recommend."

Research is ongoing. "We are acquiring more information regarding different types of inflammation in the brain, whether there is ongoing injury, and whether treatments that influence inflammation are helpful," said Meyer.

Jigsaw Puzzle

"While this is an important piece in the jigsaw puzzle of neuroinflammation in chronic neurological disease, it is important to keep in mind that we still lack understanding of the complex picture for several reasons," wrote Alexander Gerhard, MD, honorary senior lecturer in neuroscience at the University of Manchester, United Kingdom, in an accompanying editorial.^[9]

Among these reasons is that the PET technique used in the study is noisy and not restricted to glial cells, he wrote. TSPO expression is only one part of the brain's neuroinflammatory response, but PET techniques "do not currently allow us to distinguish between different states of microglial activation." In addition, "a much more detailed understanding of microglial activation at different time points" is needed before neuroinflammatory changes can be targeted therapeutically, Gerhard wrote.^[9]

Commenting on the study for Medscape, Vilma Gabbay, MD, professor of psychiatry and neuroscience and director of biomarkers and dimensional psychiatry in the Psychiatry Research Institute at Montefiore Einstein, said, "This is an important initial step to better understand the neuropsychiatric consequences of COVID even in only a mild and moderate viral illness." TSPO imaging through PET scanning has been used as an index for neuroinflammation and gliosis. Researchers have used it to study neurodegenerative diseases, but as the authors note, the ligand is not specific for gliosis.

"Follow-up large cohort studies including other measures of neuroimaging modalities assessing circuitry and neurochemistry are needed," she said. "Similarly, studying the blood-brain barrier will also allow us to better understand how the immune reaction in the blood transitions to the brain."

This field of research is evolving, and clinical trials are ongoing, Gabbay added. Meanwhile, clinicians should monitor for, assess, and treat neuropsychiatric symptoms and "follow the literature for new research and management recommendations."

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