Tag Archives: Oxygen

Study highlights two strategies used by Salmonella to escape the human body’s defenses

Like thieves that constantly look for ways to evade capture, Salmonella enterica, a disease-causing bacterium, uses various tactics to escape the human body’s defense mechanisms. In a new study, researchers from the Department of Microbiology and Cell Biology (MCB), IISc, highlight two such strategies that the bacterium uses to protect itself, both driven by the same protein.

When Salmonella enters the human body, each bacterial cell resides within a bubble-like structure known as Salmonella-containing vacuole (SCV). In response to the bacterial infection, the immune cells in our body produce reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with pathways triggered to break down these SCVs and fuse them with cellular bodies called lysosomes or autophagosomes, which destroy the bacteria. However, these bacteria have developed robust mechanisms to maintain vacuolar integrity, which is crucial for their survival. For example, when a bacterial cell divides, the vacuole surrounding it also divides, enabling every new bacterial cell to be ensconced in a vacuole. This also ensures that more vacuoles are present than the number of lysosomes which can digest them.

In the study published in Microbes and Infection, the IISc team deduced that a critical protein produced by Salmonella, known as SopB, prevents both the fusion of SCV with lysosomes as well as the production of lysosomes, in a two-pronged approach to protect the bacterium. “[This] gives the upper hand to bacteria to survive inside macrophages or other host cells,” explains Ritika Chatterjee, former PhD student in MCB and first author of the study. The experiments were carried out on immune cell lines and immune cells extracted from mice models.

SopB acts as a phosphatase – it aids in removing phosphate groups from phosphoinositide, a type of membrane lipid. SopB helps Salmonella change the dynamics of the vacuole – specifically it alters the type of inositol phosphates in the vacuole membrane – which prevents the vacuole’s fusion with lysosomes.

A previous study from the same team had reported that the number of lysosomes produced by the host cells decreases upon infection with Salmonella. The researchers also found that mutant bacteria that were unable to produce SopB were also unable to reduce host lysosome numbers. Therefore, they decided to look more closely at the role that SopB was playing in the production of lysosomes, using advanced imaging techniques.

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What they found was that SopB prevents the translocation of a critical molecule called Transcription Factor EB (TFEB) from the cytoplasm of the host cell into the nucleus. This translocation is vital because TFEB acts as a master regulator of lysosome production.

This is the first time we deciphered that SopB can work in a dual manner – it changes the phosphoinositide dynamics of SCV and affects TFEB’s translocation into the nucleus. While other groups have already reported the function of SopB in mediating invasion in epithelial cells, the novelty of our study lies in identification of the function of SopB in inhibiting the vacuolar fusion with existing autophagosomes/lysosomes, and the second mechanism, which provides Salmonella with a survival advantage by increasing the ratio of SCV to lysosomes.”

Dipshikha Chakravortty, Professor at MCB and corresponding author of the study

The researchers suggest that using small molecule inhibitors against SopB or activators of TFEB can help counter Salmonella infection.

In subsequent studies, the team plans to explore the role of another host protein called Syntaxin-17 whose levels also reduce during Salmonella infection. “How do the SCVs reduce the levels of Syntaxin-17? Do they exchange it with some other molecules, or do the bacteria degrade it? We [plan to] look into it next,” says Chakravortty.

Journal reference:

Chatterjee, R., et al. (2023) Deceiving The Big Eaters: Salmonella Typhimurium SopB subverts host cell Xenophagy in macrophages via dual mechanisms. Microbes and Infection. doi.org/10.1016/j.micinf.2023.105128.

Breathing New Life: Oxygen Therapy Improves Heart Function in Long COVID Patients

A small trial has found that hyperbaric oxygen therapy (HBOT) may help restore proper heart function in patients with post-COVID syndrome, with participants in the HBOT group experiencing a significant increase in global longitudinal strain (GLS), an indicator of heart function.

A small randomized trial in patients with post-COVID syndrome has found that hyperbaric oxygen therapy promotes the restoration of the heart’s ability to contract properly. The research is presented at EACVI 2023, a scientific congress of the European Society of Cardiology (ESC).[1]

“The study suggests that hyperbaric oxygen therapy can be beneficial in patients with long COVID,” said study author Professor Marina Leitman of the Sackler School of Medicine, Tel Aviv University and Shamir Medical Centre, Be’er Ya’akov, Israel. “We used a sensitive measure of cardiac function which is not routinely performed in all centers. More studies are needed to determine which patients will benefit the most, but it may be that all long COVID patients should have an assessment of global longitudinal strain and be offered hyperbaric oxygen therapy if heart function is reduced.”

Most COVID-19 sufferers fully recover, but after the initial illness approximately 10–20% of patients develop long COVID, also called post-COVID condition or syndrome.[2] Symptoms include shortness of breath, fatigue, cough, chest pain, rapid or irregular heartbeats, body aches, rashes, loss of taste or smell, nausea, vomiting, diarrhea, headache, dizziness, insomnia, brain fog, depression and anxiety. Patients with post-COVID syndrome may also develop cardiac dysfunction and are at increased risk of a range of cardiovascular disorders.[3]

This randomized controlled double-blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT) on the cardiac function of long COVID patients. HBOT involves inhalation of 100% pure oxygen at high pressure to increase delivery to the body’s tissues, which is particularly beneficial for tissues that are starved of oxygen due to injury or inflammation. HBOT is an established treatment for non-healing wounds, decompression sickness in divers, carbon monoxide poisoning, radiation injury, and certain types of infections

The study enrolled 60 post-COVID syndrome patients with ongoing symptoms for at least three months after having mild to moderate symptomatic COVID-19 confirmed by a PCR test. Both hospitalized and non-hospitalized patients were included. Severe COVID cases were excluded. Patients were randomized to HBOT or a sham procedure in a 1:1 ratio. Each patient had five sessions per week over eight weeks, for a total of 40 sessions. The HBOT group received 100% oxygen through a mask at a pressure of 2 atmospheres for 90 minutes, with 5 minute air breaks every 20 minutes. The sham group breathed 21% oxygen by mask at 1 atmosphere for 90 minutes. All participants underwent echocardiography at baseline (before the first session) and 1 to 3 weeks after the last session.

Echocardiography was used to assess left ventricular global longitudinal strain (GLS), which is a measure of the heart’s ability to contract and relax lengthwise. It indicates how well the heart is functioning and can help detect early signs of heart disease. A healthy heart will have a GLS value of around -20% which means that the heart muscle is able to properly contract and relax in the longitudinal direction. Reduced GLS is an early marker that the heart is not able to contract and relax effectively.

At baseline, nearly half of study participants (29 out of 60; 48%) had reduced GLS. Of those, 13 (43%) and 16 (53%) were in the sham and HBOT groups, respectively. The average GLS at baseline across all participants was -17.8%. In the HBOT group, GLS significantly increased from -17.8% at baseline to -20.2% after the intervention (p=0.0001). In the sham group, GLS was -17.8% at baseline and -19.1% after the sessions, with no statistically significant difference between the two measurements.

Professor Leitman said: “It was notable that almost half of long COVID patients had impaired cardiac function at baseline according to GLS despite all participants having a normal ejection fraction, which is the standard method for measuring the heart’s ability to contract. This means that ejection fraction is not sensitive enough to identify long COVID patients with reduced heart function.”

She concluded: “The findings suggest that HBOT promotes recovery of cardiac function in patients with post-COVID syndrome. More research is needed to collect long-term results and determine the optimal number of sessions for maximum therapeutic effect.”

Meeting: EACVI 2023


Smoking alters lung microbiome, leading to loss of diversity and community structure

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In a recent study published in the journal Access Microbiology, researchers explore the composition of the microbiome and interactions in the lower respiratory tract (LRT) in smokers. 

Study: Lower respiratory tract microbiome composition and community interactions in smokers. Image Credit: vchal / Shutterstock.com

The impact of smoking on the respiratory microbiome

Smoking has been shown to impact resident microbial communities present in different bodily regions. Previous studies have proposed various mechanisms responsible for this association, such as immunosuppression related to smoking, an increase in biofilm formation for specific species, and selection of species by the influence of local oxygen tension.

The upper airways and oral cavities may also directly interact with smoking chemicals, microbes, and heat from cigarettes, which can alter microbiome content. Recent studies have hypothesized that dysbiosis noted in the oral microbiome related to smoking may lead to a greater likelihood of experiencing complications in the respiratory tract among smokers. 

About the study

In the present study, researchers compare the LRT microbiome profiles of active smokers (AS), former smokers (FS), and non-smokers (NS) to describe the bacterial communities present in the lung.

The study involved volunteer subjects aged over 40 years of age who were either smokers of a minimum of 10 pack-years throughout their life or non-smokers. Former smokers qualified for the study if they had abstained from using tobacco for a minimum of 12 months, while AS smoked a minimum of one cigarette within three days of recruitment.

All study participants were required to complete a pulmonary function examination and thorough demographic and clinical questionnaire. The sampling process was standardized for all participants. The team extracted total deoxyribonucleic acid (DNA) from the bronchoalveolar lavages (BALs) specimens.

A single polymerase chain reaction (PCR) assessment was conducted to amplify the V6-V8 region present on the 16S ribosomal ribonucleic acid (rRNA) gene from the metagenomic DNA extracts of the BAL samples. Alpha diversity was estimated using Chao richness and inverse Simpson diversity indices. The DESeq2 algorithm was also used to detect differentiating taxa for each cohort.

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Study findings

All 46 smokers reported similar smoking exposure in terms of pack-years, including the FS quitting smoking on an average of about 10 years prior to enrollment. AS and FS exhibited reduced forced vital capacity (FVC), diffusing capacity for carbon monoxide (DL-CO), and forced expiratory volume at second 1 (FEV1); however, these variations were not remarkable according to the analysis of variance (ANOVA).

Over 3,600 reads with an average length of about 479 nucleotides were documented in each participant’s BAL, which facilitated the description of almost 400 operational taxonomic units (OTUs) per participant. The NS profile was sufficiently balanced between the prevalent phyla Bacteroides, Firmicutes, Proteobacteria, and Actinobacteria with comparatively slightly higher proportions. The FS cohort had a significant increase in Proteobacteria with reduced Bacteroides and Firmicutes levels. This pattern was also true for AS, with Proteobacteria increasing to 75% and Firmicutes declining to 11%.

Genus-level assessments indicated that most of the enhancement in Proteobacteria in AS and FS in comparison to its high proportion in NS was due to the genus Ralstonia, which increased from 2% in the NS, 28% in AS, and 21% in FS.

From the Firmicutes phylum, the Streptococcus and Veillonella genera, as well as Prevotella from the Bacteroidetes phyla exhibited the greatest decline in comparative abundance. Furthermore, the Propionibacterium genus of the Actinobacteria phylum exhibited a slight improvement from 3% in AS and FS to 0.8% in NS.

With respect to the NS profile, a greater number of upper-quartile taxa were distinguished from AS, whereas lower-quartile taxa were distinguished from FS.

NS exhibited a considerably higher mean diversity as compared to AS and FS. The mean diversity further increased when the participants were placed by declining richness, thus indicating that NS reported higher richness. Yet, the diversity evaluated with the inverse Simpson index had only an intermediate association with richness estimates and the participant’s smoking status.


The current study provides new insights into the complicated microbial communities found in the LRT and how this microbiome can be changed under different smoking conditions. The researchers also observed that the oral microbiota can settle in the lungs of smokers, which makes the study of the upper airway microbiome interesting for future research.

The microbiomes of former smokers appear to exhibit similar properties to those of both AS and NS. In the future, integration of the present findings with next-generation analytical techniques would help establish the effect of such microbial communities on human health.

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Journal reference:
  • Campos, M., Cickovski, T., Fernandez, M., et al. (2023). Lower respiratory tract microbiome composition and community interactions in smokers. Access Microbiology. doi:10.1099/acmi.0.000497.v3

Research finds SARS-CoV-2 Omicron variant to be more fatal than seasonal influenza

Adults hospitalized with the SARS-CoV-2 Omicron variant have a higher death rate than those hospitalized with seasonal influenza, even though Omicron is considered less virulent with lower case fatality rates than the delta and alpha strains, new research being presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Copenhagen, Denmark (15-18 April) suggests.

The study by Dr Alaa Atamna and colleagues from the Rabin Medical Center at Belinison Hospital in Israel found that adults (18 years or older) hospitalized with influenza were 55% less likely to die within 30 days than those hospitalized with Omicron during the 2021-2022 influenza season.

Influenza and COVID-19 are both respiratory diseases with similar modes of transmission. In December 2021, influenza re-emerged in Israel after it went undetected since March 2020. At the same time, the Omicron had substituted Delta as the predominant variant. But data directly comparing Omicron with seasonal influenza are scarce.

To find out more, researchers compared the clinical outcomes of patients hospitalized with COVID-19 (Omicron variant) and those hospitalized with influenza at a large academic hospital in Israel.

Consecutive patients hospitalized with laboratory confirmed COVID-19 (167 patients; average age 71 years, 58% male) and influenza infection (221 patients; average age 65 years, 41% male) during December 2021 and January 2022 were included in the study.

Overall, 63 patients died within 30 days-;19 (9%) admitted with influenza and 44 (26%) hospitalized with Omicron.

Patients with Omicron tended to have higher overall comorbidity scores, needed more assistance performing activities of daily living (e.g., washing and dressing), and were more likely to have high blood pressure and diabetes, whereas asthma was more common in those hospitalized with influenza (see table 1 in notes to editors).

Respiratory complications and need for oxygen support and mechanical ventilation were also more common in Omicron cases than in seasonal influenza.

A possible reason for the higher Omicron death rate is that patients admitted with Omicron were older with additional major underlying illnesses such as diabetes and chronic kidney disease. The difference might also be due to an exaggerated immune response in COVID-19, and that vaccination against COVID-19 was far lower among patients with Omicron.”

Dr Alaa Atamna, Rabin Medical Center at Belinison Hospital in Israel

He continues, “The double whammy of overlapping influenza and COVID-19 epidemics will increase the complexity of disease and the burden on health systems. There is one basic step people can take that may alter the trajectory of either epidemic, get the vaccines for flu and COVID-19, especially if you are older and have underlying illnesses.”

The authors point out that the study was observational so can’t prove causation, and it was conducted in one hospital in Israel so the results may not apply to other countries and populations. And they cannot rule out the possibility that other unmeasured factors such as influenza and COVID19 vaccination status may have influenced the results. They also note that the excess mortality observed for Omicron could be the result of an influenza season that was less severe than usual. Finally, the study included only hospitalized patients, so could not estimate the proportion of hospitalized patients in the total number of infected patients.

Novel subset of memory B cells predicts long-lived antibody responses to influenza vaccination

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.

Journal reference:

Nellore, A., et al. (2023). A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans. Immunity. doi.org/10.1016/j.immuni.2023.03.001.

Vaginal sex can shape the composition of urethral microbiome in healthy men

Contrary to common beliefs, your urine is not germ free. In fact, a new study shows that the urethra of healthy men is teeming with microbial life and that a specific activity-;vaginal sex-;can shape its composition. The research, published March 24 in the journal Cell Reports Medicine, provides a healthy baseline for clinicians and scientists to contrast between healthy and diseased states of the urethra, an entrance to the urinary and reproductive systems.

We know where bugs in the gut come from; they primarily come from our surroundings through fecal-oral transfer. But where does genital microbiology come from?”

David Nelson, co-senior author, microbiologist at Indiana University

To flush out the answer, the team of microbiologists, statisticians, and physicians sequenced the penile urethra swabs of 110 healthy adult men. These participants had no urethral symptoms or sexually transmitted infections (STIs) and no inflammation of the urethra. DNA sequencing results revealed that two types of bacterial communities call the penile urethra home-;one native to the organ, the other from a foreign source.

“It is important to set this baseline,” says co-senior author Qunfeng Dong, a bioinformatician at Loyola University Chicago. “Only by understanding what health is can we define what diseases are.”

The researchers found that most of the healthy men had a simple, sparse community of oxygen-loving bacteria in the urethra. In addition, these bacteria probably live close to the urethral opening at the tip of the penis, where there is ample oxygen. The consistent findings of these bacteria suggest that they are the core community that supports penile urethra health.

But some of the men also had a more complex secondary group of bacteria that are often found in the vagina and can disturb the healthy bacterial ecosystem of the vagina. The team speculates that these bacteria reside deeper in the penile urethra because they thrive in oxygen-scarce settings. Only men who reported having vaginal sex carry these bacteria, hinting at the microbes’ origins.

Delving into the participant’s sexual history, the team found a close link between this second bacterial community and vaginal sex but not other sexual behaviors, such as oral sex and anal sex. They also found evidence that vaginal sex has lasting effects. Vagina-associated bacteria remained detectable in the participants for at least two months after vaginal sex, indicating that sexual exposure to the vagina can reshape the male urinary-tract microbiome.

“In our study, one behavior explains 10% of the overall bacterial variation,” says Nelson, when discussing the influence of vaginal sex. “The fact that a specific behavior is such a strong determinant is just profound.”

Although current findings from the study show that vaginal bacteria can spread to the penile urethra, the team’s next plan is to test whether the reverse is true. Using the newly established baseline, the researchers also hope to offer new insights into bacteria’s role in urinary- and reproductive-tract diseases, including unexplained urethral inflammation and STIs.

“STIs really impact people who are socioeconomically disadvantaged; they disproportionately impact women and minorities,” says Nelson. “It’s a part of health care that’s overlooked because of stigma. I think our study has a potential to dramatically change how we handle STI diagnosis and management in a positive way.”

This work was supported by the National Institute of Allergy and Infectious Diseases.

Journal reference:

Toh, E., et al. (2023). Sexual behavior shapes male genitourinary microbiome composition. Cell Reports Medicine. doi.org/10.1016/j.xcrm.2023.100981

Long COVID, a new clinical entity constantly evolving

A recent Journal of Microbiology, Immunology, and Infection study discusses the epidemiology, diagnosis, pathogenesis, and treatment of long coronavirus disease 2019 (COVID-19).

Study: Long COVID: An inevitable sequela of SARS-CoV-2 infection. Image Credit: fizkes / Shutterstock.com

Study: Long COVID: An inevitable sequela of SARS-CoV-2 infection. Image Credit: fizkes / Shutterstock.com

What is long COVID?

COVID-19 manifests as mild or asymptomatic illness in most patients; however, some patients develop severe disease or acute respiratory distress syndrome (ARDS), even following receipt of antiviral treatments and/or vaccines. Even after recovery from severe COVID-19, some patients have reported persistent symptoms that have been collectively referred to as long COVID, post-COVID-19, or post-acute sequelae of COVID-19 (PASC).

Long COVID may be defined in multiple ways, such as the presence of symptoms that have persisted beyond three weeks after initial symptom onset or the development of symptoms unexplained by an alternative diagnosis lasting for more than four weeks. The present study provides an overview of the current understanding of long COVID.

Epidemiology and risk factors of long COVID

A meta-analysis of 50 studies estimated the global prevalence of long COVID at 28 days or more to be 43%. Asia had the highest prevalence at 51%, followed by Europe and America.

Another meta-analysis reported that over 63% and 71% of patients had at least one post-COVID-19 symptom after 30 and 60 days post-onset/hospitalization, respectively. One study observed that the prevalence of long COVID among children and adolescents was 25.24%, whereas the rate of long COVID was 29.19% for hospitalized patients.

Furthermore, an Italian study revealed that long COVID prevalence in healthcare workers varied across COVID-19 pandemic waves. One United States study on veterans indicated that vaccine-breakthrough infections exhibited an elevated risk of post-acute sequelae, including gastrointestinal, cardiovascular, mental health, neurologic, and hematologic disorders. Another retrospective study identified age and severe disease as factors associated with a higher risk of experiencing at least three symptoms at one-year follow-up.

Clinical manifestations and mechanisms of long COVID

Long COVID can affect multiple organs, with one study concluding that respiratory, cardiovascular, and neuropsychological symptoms were most frequently reported in COVID-19 survivors. Numerous studies have identified fatigue as the most prevalent systemic symptom. Mood swings are most frequently reported in children and young adults.

Shortness of breath, post-activity polypnea, dyspnea, chest distress, pain while breathing, cough, and polypnea are common respiratory symptoms of long COVID. Common neurologic manifestations include brain fog, memory impairment, paresthesia, dysnomia, vertigo, headache, poor attention span, bradykinesia, anhedonia, and anguish.

In addition, psychosocial symptoms such as depression, anxiety, psychosis, post-traumatic stress disorder (PTSD), and behavioral disorder have also been reported. One meta-analysis observed anxiety and depression in 22% and 23% of long COVID patients, respectively. Memory loss/complaints, forgetfulness, and difficulty concentrating and sleeping were also prevalent in this study.

One study found elevated interleukin 2 (IL-2) and IL-17 levels, as well as reduced IL-4, IL-6, and IL-10 levels, in long COVID patients relative to those without any sequelae. Several biomarkers were found to be associated with neurologic sequelae, of which included angiotensin-converting enzyme 2 (ACE2), IL-17, transmembrane protease serine 2 (TMPRSS2), zonulin, and interferon (IFN)-γ.

The explicit mechanisms of long COVID remain poorly defined given its novelty. However, several mechanisms have been theorized, of which include damage to ACE2-expressing organs by SARS-CoV-2, inflammation due to persistent viral reservoir post-infection resolution, host responses such as over-production of cytokines, auto-immunity, and delayed inflammation resolution affecting homeostatic milieu of the organ(s), among others.

Vaccines, diagnosis, and potential treatment

One prospective case-control study reported that individuals were less likely to report persistent symptoms after receiving a second COVID-19 vaccine dose than non-vaccinated individuals. An Italian observational cohort study observed that BNT162b2 vaccination was associated with a lower prevalence of long COVID that decreased with the number of vaccine doses administered.

The appropriate diagnostic criteria for long COVID are unclear, as the condition can manifest with non-specific symptoms and involve multiple organ systems. Nevertheless, the diagnosis should be guided by the patient’s history, physical examination, and clinical manifestations. Functional status and quality of life can be assessed using a post-COVID-19 function status scale and patient-reported outcome measurement information system.

Montreal cognitive assessment, Compass 31, mini-mental status examination, and neurobehavioral system inventory may be used to evaluate neurologic conditions. Electrocardiograms, echocardiograms, pulmonary function tests, or chest radiography may be helpful for new cardiac or respiratory concerns.

Long COVID management warrants prompt a multi-disciplinary assessment that focuses on managing specific symptoms and supporting rehabilitation. Hyperbaric oxygen therapy (HBOT) is also a potential therapeutic modality.

Several trials are currently investigating the effects of physiotherapy, physical rehabilitation, neurorehabilitation, and cognitive interventions. These studies may provide more conclusive evidence in the future.

Concluding remarks

The number of long COVID cases may increase as the number of COVID-19 cases continues to rise worldwide. Based on currently available information, long COVID could develop in all COVID-19 patients, although severe patients are at an increased risk.

Furthermore, long COVID could present with heterogeneous clinical manifestations, with vaccination potentially being the only way to avert long COVID. Future studies are needed using established diagnostic and definition criteria to gain more insights into long COVID.

Journal reference:
  • Lai, C. C., Hsu, C. K., Yen, M. Y., et al. (2022). Long COVID: An inevitable sequela of SARS-CoV-2 infection. Journal of Microbiology, Immunology and Infection. doi:10.1016/j.jmii.2022.10.003

The microorganisms of the world are in constant conflict, battling for resources and space in a microbial arms …

The microorganisms of the world are in constant conflict, battling for resources and space in a microbial arms race. Some viruses can infect amoeba, while others might infect archaea or bacteria. There are even bacteria that can prey on other bacteria. Scientists have now discovered a bacterium that stalks cyanobacteria in the earth’s biocrusts. These newly identified predators, called Candidatus Cyanoraptor togatus (C. togatus), or Cyanoraptor, can attack cyanobacteria living in desert soil.

After infecting its prey, Cyanoraptor begins to replicate until it kills the prey, releasing a new army of attackers. / Credit: Photo courtesy of Julie Bethany Rakes

Cyanobacteria are photosynthetic, and play a role in the production of oxygen and nitrogen fixing in the environment, processes that many other organisms rely on. Cyanobacteria also form biocrusts, which are beneficial communities of cells that live on the surface of soil. They help prevent erosion, trap dust, and increase nutrient and water levels in the soil. Though they are important to the desert ecosystem, they are also targeted.

“There was something killing the biocrusts. It was not a virus, and it was not a small animal. It could only be another bacterium,” said Professor Ferran Garcia-Pichel of Arizona State University.

Biocrusts usually look like soil. But after a Cyanoraptor attack, circular rings appear in which the cyanobacteria have been eliminated. Researchers identified them in the field, then assessed them in the lab, revealing more about Cyanoraptor. The findings have been reported in Nature Communications.

Julie Bethany Rakes noticed something amiss in plaques, where cyanobacteria had disappeared. She continued investigating. / Credit: Photo courtesy of Julie Bethany Rakes

In their early stages, Cyanoraptor cells are small and spherical; these so-called propagules just wait for their prey, not growing or dividing. If a cyanobacterium gets close, the Cyanoraptor attacks by binding to its prey with a docking structure. The cell wall of the prey cyanobacterium dissolves, and the predator Cyanoraptor enters the cyanobacterial cell and starts consuming it. Cyanoraptor continues to grow larger, then divides into many new cells once it reaches a certain size. The prey cell dies, and Cyanoraptor transforms into propagules once more until another victim comes along.

The desert ecosystem loses the benefits provided by cyanobacterium as more get consumed by Cyanoraptor. “In general, this means that there could be serious consequences for desert health, fewer nutrients, less stable soil and water retention so a reduction in time plants and other organisms can be active. With the loss of these functions, organisms that rely on these services, such as plants may suffer, which could then have further consequences up the food chain,” explained first study author Julie Bethany Rakes, PhD.

Sources: Arizona State University, Nature Communications

Carmen Leitch