Tag: SARS

  • Survey of US adults reveals common cognitive symptoms in post-COVID-19 patients, linked to impaired daily functioning and depression

    Survey of US adults reveals common cognitive symptoms in post-COVID-19 patients, linked to impaired daily functioning and depression

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    In a recent study published in the journal JAMA Network Open, a team of scientists examined how prevalent self-reported cognitive symptoms were in individuals with post-coronavirus disease 2019 (COVID-19) condition as compared to individuals who had prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections but had not developed post-COVID-19 condition. They also evaluated the impact of these cognitive symptoms on mood, function, and employment status.

    Study: Cognitive Symptoms of Post–COVID-19 Condition and Daily Functioning. Image Credit: PeopleImages.com - Yuri A/Shutterstock.com
    Study: Cognitive Symptoms of Post–COVID-19 Condition and Daily Functioning. Image Credit: PeopleImages.com – Yuri A/Shutterstock.com

    Background

    One of the long-term impacts of the COVID-19 pandemic has been post-COVID-19 condition, commonly referred to as long coronavirus disease (long COVID), where the symptoms of acute SARS-CoV-2 infections persist or remerge months after recovering from the initial infection. The condition consists of wide-ranging symptoms affecting numerous organ systems, with fatigue, shortness of breath, and post-exertional malaise being the most common symptoms.

    Changes in mood and cognitive impairments have also been reported, with studies confirming the long-lasting impact of SARS-CoV-2 infections on neurological health. These persistent physical and neurological symptoms continue to have a significant impact on the functioning and quality of life of the patients long after they have recovered from the initial infection. Understanding how this condition impacts the individual’s productivity or employment status is essential to forming effective treatment mechanisms and public health strategies.

    About the study

    In the present study, the researchers used data from a survey conducted across the United States (U.S.) during two COVID-19 waves among individuals who had reported post-COVID-19 condition symptoms and those who reported complete recovery after a SARS-CoV-2 infection. The data was collected between December 2022 and January 2023 and then again from April to May 2023 across 50 U.S. states.

    The participants were above 18 years of age, and the study population was balanced for demographic factors such as gender, age, race, and ethnicity. A validated measure for patient-reported outcomes was used to design the questions on cognitive symptoms, which largely included questions on how often patients experienced specific symptoms over the previous week with replies on a five-point scale.

    The questions addressed the prevalence of symptoms such as trouble remembering, trouble starting tasks, slowed thinking, finding multitasking difficult, decision-making problems, and needing to pay extra attention to avoid errors. The number of symptoms and presence of these symptoms based on an occurrence rate of at least once a day were recorded for each patient.

    A nine-item questionnaire was also used to assess depressive symptoms in patients. Additionally, the patients were asked to describe how these cognitive post-COVID-19 symptoms interfered with their daily activities. The employment status of the participants was also recorded and categorized as full-time, contract, part-time, self-employed, homemaker, student, retired, or unemployed.

    Sociodemographic information collected from the participants included self-reported race and ethnicity data. The initial SARS-CoV-2 infection and post-COVID-19 condition were defined based on self-reported symptoms from the participants, such as reports of positive test results for COVID-19.

    Results

    The results showed that cognitive symptoms were prevalent in individuals experiencing post-COVID-19 conditions, and these symptoms were associated with functional impairments and a lower likelihood of holding full-time employment. The severity of depressive symptoms was also greater for individuals with cognitive post-COVID-19 symptoms.

    The number of individuals with post-COVID-19 condition who reported experiencing cognitive impairments was significantly higher than those who reported cognitive symptoms but did not have post-COVID-19 condition. Furthermore, women, younger individuals, and people with lower income levels showed a higher prevalence of cognitive symptoms than those in other sociodemographic groups.

    The researchers believe that the higher prevalence of cognitive impairments reported among younger individuals could be due to the notable change from the baseline measurements before the COVID-19 pandemic. Among older individuals, who might already be experiencing cognitive decline associated with age, the cognitive impairments due to post-COVID-19 condition might not be as apparent as in younger individuals.

    The study also suggested that the association between increased prevalence of cognitive impairments among individuals from lower-income households could reflect the influence of economic stress on the vulnerability to cognitive symptoms of post-COVID-19 conditions.

    Conclusions

    Overall, the study found that cognitive decline was highly prevalent among individuals with long COVID or post-COVID-19 conditions, especially among younger individuals, women, and those from low-income households.

    Furthermore, the probability of full-time employment was found to be lower among individuals experiencing cognitive impairments due to long COVID, highlighting the need for public health strategies and treatment measures to improve the quality of life and functional abilities of individuals suffering from post-COVID-19 condition.

    Journal reference:

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  • Study reveals seasonal MERS-CoV peaks in Kenyan camels and potential human transmission

    Study reveals seasonal MERS-CoV peaks in Kenyan camels and potential human transmission

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    In a recent study published in the CDC’s journal Emerging Infectious Diseases, researchers estimated the incidence and potential human transmission of the Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedaries (nomadic camels) in northern Kenya. They found that the incidence of MERS-CoV among these animals was biphasic, peaking in October 2022 and February 2023. Further, slaughterhouse workers in contact with the dromedaries were found to show serologic signs of exposure to MERS-CoV.

    Dispatch: Biphasic MERS-CoV Incidence in Nomadic Dromedaries with Putative Transmission to Humans, Kenya, 2022–2023. Image Credit: Hamady / ShutterstockDispatch: Biphasic MERS-CoV Incidence in Nomadic Dromedaries with Putative Transmission to Humans, Kenya, 2022–2023. Image Credit: Hamady / Shutterstock

    Background

    MERS-CoV is prevalent in dromedary camels in the Arabian Peninsula and Africa, with >75% seroprevalence. Zoonotic transmission to humans, mainly in the Arabian Peninsula, has resulted in >2,400 cases and >800 deaths so far. Although camel breeding is a major activity in Kenya, only three cases of MERS-CoV were identified in camel-exposed humans in 2019, suggesting regional epidemiologic differences.

    MERS-CoV outbreaks in farmed dromedary camels are linked with annual camel parturition, with calves testing positive for MERS-CoV ribonucleic acid (RNA) after losing maternal antibodies. Nomadic camels in Africa, with fluctuating population densities due to seasonality and food availability, have shown correlations between high population density and MERS-CoV seropositivity in Kenya, indicating gaps in our understanding of MERS-CoV circulation.

    Limited infrastructure hinders field studies on nomadic camels, but the regular transportation of these animals to slaughterhouses allows for continuous testing. Leveraging this setup, researchers in the present study conducted a year-long study at a northern Kenyan slaughterhouse hub to estimate the MERS-CoV incidence in dromedaries and their potential transmission to individuals working there.

    About the study

    The study was conducted at a slaughterhouse hub in Isiolo, northern Kenya. Sampling was conducted from September 2022 to September 2023. Samples were collected from 10-15 dromedary camels at a frequency of 4-5 days per week. The camels (n = 2,711) originated from various administrative wards (n=12), primarily from Laisamis and Burat.

    MERS-CoV RNA detection was performed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Confirmation was done by open reading frame (ORF) 1ab qRT-PCR or sequencing. Phylogenetic analysis was additionally performed. Randomized camel serum samples (n = 369) were tested to assess MERS-CoV immunoglobulin G (IgG) levels using ELISA (short for enzyme-linked immunosorbent assay). Optical density ratio (ODR) values were obtained. Statistical analyses were conducted to explore the associations between MERS-CoV IgG levels, RNA-positivity, seasonality, camel sex, and age.

    Sero-epidemiologic investigation was conducted among slaughterhouse workers in contact with dromedaries. MERS-CoV S1 IgG reactivity was assessed using ELISA. Potential cross-reactivity with SARS-CoV-2 antibodies was excluded by comparing ELISA ODRs between MERS-CoV S1 and SARS-CoV-2 S1 assays. Neutralization tests (NT) were conducted using green fluorescent protein (GFP)–encoding vesicular stomatitis virus pseudoparticles (VSVpp) carrying MERS-CoV S protein from two clades. Testing was performed on seven serum samples at a 1:20 dilution. A plaque-reduction neutralization test (PRNT) based on MERS-CoV EMC/2012 was conducted.

    Results and discussion

    MERS-CoV RNA was detected in 1.3% of camels. The cumulative RNA positivity rate was found to be higher in September-October 2022 (5.0%) compared to January-March 2023 (2.3%). Incidence showed biphasic peaks in October 2022 and February 2023. Phylogenetic analysis revealed high similarity (>99.93% nucleotide identity) with MERS-CoV strains from Akaki, Ethiopia, in 2019. The sequences clustered within clade C2.2, which includes strains initially identified in Kenya in 2018, indicating three putative MERS-CoV outbreaks in Kenyan camels.

    MERS-CoV IgG levels had a median ODR of 2.14, with a seroprevalence of 80.76%. IgG levels were lowest in June and highest in March. A negative association was found between MERS-CoV IgG levels and RNA positivity. RNA-positivity was found to be negatively linked to the season. Compared to female camels, male camels showed a greater probability of being RNA-positive and a lower probability of being seropositive. Older animals (>3 years) had a higher (but statistically insignificant) seropositivity rate (86%) compared to animals ≤3 years (72%).

    MERS-CoV S1 IgG reactivity was detected in 14.6% of Isiolo abattoir workers. The absence of MERS-CoV S1 IgG reactivity was noted in a control cohort (n = 12) without camel exposure despite high SARS-CoV-2 S1 IgG levels (92%). Notably, one serum sample showed a VSVpp-NT 50–90% reduction of foci-forming units. Additionally, results from PRNT confirmed MERS-CoV seroconversion for the sample. None of the MERS-CoV ELISA-negative samples demonstrated neutralizing capacity in VSVpp-NT and PRNT assays.

    Conclusion

    In conclusion, the present study revealed a biphasic incidence of MERS-CoV in dromedary camels, potentially influenced by increased animal interactions during transport and seasonal factors. The evidence of human transmission in the study highlights the need for enhanced surveillance and preventive measures to mitigate zoonotic transmission risk. Further research is warranted to investigate the dynamics of MERS-CoV circulation and formulate strategies for potential disease control and prevention.

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  • New study pinpoints key markers for Long COVID diagnosis

    New study pinpoints key markers for Long COVID diagnosis

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    In a recent preprint* uploaded to the medRxiv server, an international team of researchers conducted a large-scale systems-level immunological screening of more than 1,000 confirmed COVID-19 patients to identify diagnostic markers of Long-term COVID-19. The analyses using multiple orthogonal detection methods reveal elevated serologic responses as a highlight of Long COVID and that its correlated memory CD8+ T cell clonal expansion is a more reliable and sensitive marker of the condition than conventional antigen (SARS-CoV-2 RNA and protein) detection approaches.

    Study: Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID. Image Credit: Lightspring / ShutterstockStudy: Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID. Image Credit: Lightspring / Shutterstock

    *Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

    COVID-19 and the need for Long COVID diagnosis

    The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused Coronavirus disease 2019 (COVID-19) viral pandemic is one of the worst in human memory, estimated to have infected more than 700 million individuals since its discovery in Wuhan, China, in late 2019. While global legislative policy and the widespread development and dissemination of anti-COVID-19 vaccines have substantially reduced the disease burden, with reports of vaccination efforts saving 70% of patients or more, survivors of the pandemic are plagued by a hitherto unknown condition – Long COVID.

    Also called the ‘Post COVID-19 condition’, ‘chronic COVID syndrome,’ and clinically, ‘post-acute sequelae of COVID-19 (PASC)’, Long COVID presents itself as perhaps the worst legacy of the pandemic. The now well-established yet poorly understood condition is characterized by the persistence or development of COVID-19-associated symptoms that may persist for months or even years following initial infection recovery. These symptoms include severe cognitive decline (brain fog), chronic fatigue, and multiple organ damage, resulting in significant economic and quality of life (QoL) losses in patients.

    Alarmingly, research has revealed that despite vaccination efforts substantially reducing adverse Long COVID outcomes, between 30 and 60% of all COVID-19 infections result in Long COVID, with an estimated 350+ million individuals suffering from the condition. Unfortunately, extensive global scientific efforts remain unable to elucidate the mechanisms underpinning Long COVID, hampering the development of diagnostic assays and clinical interventions for patients.

    About the study

    In the present study, researchers screened more than 1000 prospective patients enrolled at Long COVID clinics in Belgium and Sweden to elucidate the shared mechanisms of Long COVID pathology and subsequently develop a sensitive and reliable diagnostic test for the condition. Only subjects with a clinically confirmed mild or moderate COVID-19 infection were included. Severe cases were excluded due to overlapping symptoms with those of the post-intensive care syndrome.

    Patients without objective measures of disease-associated organ damage (e.g., magnetic resonance imaging [MRI], pulsatile arterial tonometry [EndoPAT], and postural orthostatic tachycardia syndrome [POTS]) were excluded. Inclusion and exclusion criteria resulted in a final sample cohort of 121 patients from Belgium (n = 31) and Sweden (n = 90).

    Experimental procedures included the enzyme-linked immunosorbent assay (ELISA) for detecting and measuring patients’ antibody responses against SARS-CoV-2. Since these standard ELISAs were not observed to elucidate differences in immunoglobulin A (IgA) and IgM despite clear case-convalescent control differences in IgG titers, single-molecule array (SIMOA) assays were employed. The SPEAR immunoassay was used to detect the presence of persistent SARS-CoV-2 spike proteins in patients’ plasma samples.

    Since these assays revealed that antigen responses were only depicted by about 10% of the study cohort, suggesting its unreliability and poor sensitivity as a diagnostic tool, researchers used a 51-parameter-panel mass cytometry assay to investigate possible immunological correlates. The Olinks assay was further conducted to measure levels of cytokines and other plasma proteins in patients’ plasma samples.

    “Autoantibodies to type-I IFN have been associated with life-threatening COVID-19 pneumonia due to impaired IFN-I-mediated inhibition of viral replication. Such autoantibodies increase in frequency with age, are more common in males than females for unknown reason, and could explain up to 20% of COVID-19 deaths. The reasons for the development of anti-cytokine autoantibodies are unknown in most cases, but most, if not all, patients with inborn errors of central tolerance due to AIRE deficiency in cis (APECED or APS1) or in trans (mutations of the alternative NF-kB pathway) all carry these autoantibodies and are highly susceptible to severe SARSCoV-2 infections.”

    To investigate the above, single-cell T-cell receptor (TCR) and message RNA (mRNA) sequencing of peripheral blood mononuclear cells (PBMCs) was carried out. Memory CD8 T cell TCR sequences were then clustered using the GLIPH methodology.

    Study findings

    The present study reveals that, while IgG response to SARS-CoV-2 spike (receptor binding domain [RDB]) proteins as measured by the SIMAO assay can be used as a sensitive Long COVID marker, IgA and IgM cannot due to their detection in ~10% of afflicted patients. This suggests that memory CD8+ T cells were restrained, and their clonal expansion is restricted by SARS-CoV-2, inconsistent with the previously hypothesized exhausted phenotype pathology.

    Strong and persistent Long COVID symptoms despite high IgG tirtes suggest differences between the initial and long-term adaptive responses of patients’ immunity to SARS-CoV-2.

    “A strong initial adaptive response might increase the chance of viral clearance and reduce the risk of Long COVID, while a sustained and elevated long-term response to SARSCoV-2 with elevated titers occur once a viral reservoir has been established leading to chronic antigen stimulation.”

    Results highlight that in Long COVID cases, the elevated serologic response was inversely correlated to expanding CD8+ T cell populations, elucidating the role of the restrained antiviral T cell response as a crucial component of Long COVID pathology. Current and future work aimed at understanding the genetic basis of this revelation may allow for the development of clinical therapeutics capable of treating this hitherto incurable condition.

    Conclusions

    The present study uses a combination of ELISA, SIMOA, and sequencing assays to investigate the associations between circulating immunoglobulin titers and Long COVID pathology, with the dual aim of elucidating Long COVID’s mechanism of action and progressing the discovery of a universal Long COVID diagnostic test. Their findings reveal that contrary to expectation, IgG titers in Long COVID patients increase following initial infection recovery, suggesting chronic antigen stimulation.

    IgA and IgM titers, in contrast, were extremely low and detectable in only 10% of cases, making them unreliable in Long COVID diagnosis.

    *Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

    Journal reference:

    • Preliminary scientific report.
      Lucie Rodriguez, Ziyang Tan, Lakshmi Kanth Tadepally, Jun Wang, Hugo Barcenilla, Zoe Swank, Fanglei Zuo, Hassan Abolhassani, Ana Jimena Pavlovitch-Bedzyk, Chunlin Wang, Laura Gonzalez, Constantin Habimana Mugabo, Anette Johnsson, Yang Chen, Anna James, Jaromir Mikes, Linn Kleberg, Christopher Sundling, Mikael Bjornson, Malin Nygren-Bonnier, Marcus Stahlberg, MIchael Runold, Sofia Bjorkander, Erik Melen, Isabelle Meyts, Johan Van Weyenbergh, Qiang Pan Hammarstrom, Mark M Davis, David R. Walt, Nils Landegren, COVID Human Genetic Effort, Alessandro Aiuti, Giorgio Casari, Jean-Laurent Casanova, MARC JAMOULLE, Judith Bruchfeld, Petter Brodin. Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID. medRxiv (2024), DOI – 10.1101/2024.02.11.24302636, https://www.medrxiv.org/content/10.1101/2024.02.11.24302636v1

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  • Study suggests patients with severe long COVID present with variable symptoms, do not cluster in relation to organs affected or immunological states

    Study suggests patients with severe long COVID present with variable symptoms, do not cluster in relation to organs affected or immunological states

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    A new preprint, recently uploaded to the medRxiv* preprint server, reports significantly associated findings that may help predict severe long COVID and understand what causes it.

    Study: Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID. Image Credit: Anucha Naisuntorn/Shutterstock.com
    Study: Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID. Image Credit: Anucha Naisuntorn/Shutterstock.com

    *Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

    Background

    SARS-CoV-2 infection causes protean manifestations extending over a wide range of severity. In the most severe cases, multiorgan failure and death supervene, with underlying coagulation failure and hyperinflammation. The key factor is the occurrence of an antiviral type-1 interferon (IFN-1) response to infection of respiratory epithelial cells and antigen-presenting dendritic cells, as this is responsible for further events that limit viral replication. In addition, it allows immune clearance of the virus.

    A type of post-COVID sequel among children has been termed the Multisystem Inflammatory Syndrome in Children (MIS-C). The occurrence of this condition is associated with the persistence of the virus in the gut, perhaps linked to chronic T cell activation.

    The resemblance to superantigen-induced T cell activation did not escape notice, especially as a superantigen-like motif had already been reported in the SARS-CoV-2 spike protein with similarity to staphylococcal enterotoxin B. Coupled with potential genetic defects associated with MIS-C, the authors speculate a common origin for both long COVID and MIS-C.

    According to them, “disease tolerance, restrained antiviral T cell responses and viral persistence” comprise one such possibility. They believe that in select groups, such as children and women of reproductive age, efficient antiviral responses ensure mild infections by limiting systemic inflammation and T cell responses. On the flip side, this increases the odds of viral persistence and, thus of long COVID.

    Evidence for viral persistence is scanty, including the presence of viral antigens in blood and tissue samples and imaging reports, as well as finding continued somatic hypermutation in B cells specific to this virus. Again, vaccination against COVID-19 reduces the risk of long COVID, as does early antiviral therapy, supporting the hypothesis that this sequel results from viral persistence.

    The current report centers on patients who had mild to moderate COVID-19 and later developed severe long COVID.  

    What did the study show?

     The scientists examined only patients with documented mild to moderate SARS-CoV-2 infection who had not been hospitalized over a thousand of them. From these, they selected those who had evidence of organ damage to the heart, blood vessels, autonomic nervous system, hyperventilation, or changes in computerized tomography (CT) of the lungs.

    These were chosen since they provided objective proof of organ damage, supporting the diagnosis of severe long COVID. They found ~120 cases, almost 90% being females with the mean age being 48 years.

    They found that there is no common set of symptoms, signs of organ damage, or characteristic immunological profile in patients who develop long COVID. However, serum antibody responses were markedly higher in these patients compared to those who recovered rapidly. This is a sign of persistent antigen stimulation, especially as these cases were sampled long after the acute infection.

    When viral RNA and protein antigens were looked for in plasma samples, using an array of independent testing methods, the researchers found that only a subset of patients were positive for viral antigens by any of the methods used. There was little overlap in the results between different assays. This indicates that blood tests for viral persistence may not yield uniform results, and the finding of elevated antibody levels is a more sensitive marker of long COVID.

    The failure to detect antigens by all assays could either reflect the decreased sensitivity of the tests or the fact that the virus harbored in the tissue reservoirs may not leak the antigens into the bloodstream. It is unlikely that failure of viral persistence is the reason, given the persistent increase in anti-SARS-CoV-2 IgG responses observed in multiple cohorts.

    They also found certain monocyte subsets and plasma proteins associated with an ongoing innate immune response at elevated levels. Such elevations were in proportion to increased immunoglobulin G (IgG) antibody titers, a marker of persistent inflammation.

    In contrast, there was a failure of expansion of cytotoxic memory CD8+ T cells targeting SARS-CoV-2. The frequency of such clones decreases as antibody levels rise.

    This suggests that individuals who fail to mount a clonally expanded memory CD8+ T cell response to SARS-CoV-2 develop a viral reservoir with persistent antigen.”

    The researchers did not find autoantibodies to IFN-1 in these patients. However, these have been found in life-threatening COVID-19-associated pneumonia and account at least in part for one in five deaths due to COVID-19 by inhibiting IFN-1-mediated suppression of viral replication.

    This indicates that the underlying mechanism of long COVID is viral persistence, with impaired CD8+ T cell responses being the norm, rather than T cell exhaustion, as some scientists have suggested earlier to be characteristic of severe long COVID.

    What are the implications?

    The study suggests that the finding of elevated SARS-CoV-2-specific IgG sensitively identifies long COVID mounted against the spike antigen. Secondly, this is likely to be the result of viral persistence with chronic antigen stimulation.

    Those patients who respond strongly to the initial infection via an adaptive immune response likely clear the virus rapidly and have a lower chance of long COVID. In contrast, if a viral reservoir is established, chronic stimulation by viral antigens leads to a long-term elevation of anti-SARS-CoV-2 IgG.

    The researchers continue to seek the reason for the failure of viral clearance in some patients leading to long COVID. Until then, prolonged administration of antivirals may be the best way to treat these patients by removing the viral reservoir.

    *Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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  • Maternal mRNA COVID-19 vaccination shields infants for six months

    Maternal mRNA COVID-19 vaccination shields infants for six months

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    Women who receive an mRNA-based COVID-19 vaccination or booster during pregnancy can provide their infants with strong protection against symptomatic COVID-19 infection for at least six months after birth, according to a study from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. These findings, published in Pediatrics, reinforce the importance of receiving both a COVID-19 vaccine and booster during pregnancy to ensure that infants are born with robust protection that lasts until they are old enough to be vaccinated.

    COVID-19 is especially dangerous for newborns and young infants, and even healthy infants are vulnerable to COVID-19 and are at risk for severe disease. No COVID-19 vaccines currently are available for infants under six months old. Earlier results from the Multisite Observational Maternal and Infant COVID-19 Vaccine (MOMI-Vax) study revealed that when pregnant volunteers received both doses of an mRNA COVID-19 vaccine, antibodies induced by the vaccine could be found in their newborns’ cord blood. This suggested that the infants likely had some protection against COVID-19 when they were still too young to receive a vaccine. However, researchers at the NIAID-funded Infectious Diseases Clinical Research Consortium (IDCRC), which conducted the study, did not know how long these antibody levels would last or how well the infants would actually be protected. The research team hoped to gather this information by following the infants through their first six months of life.

    In this portion of the study, researchers analyzed data from 475 infants born while their pregnant mothers were enrolled in the MOMI-Vax study. The study took place at nine sites across the United States. It included 271 infants whose mothers had received two doses of an mRNA COVID-19 vaccine during pregnancy. The remaining 204 infants in the study were born to mothers who had received both doses of an mRNA COVID-19 vaccine as well as a COVID-19 booster. To supplement data gathered during pregnancy and at birth, the infants were evaluated during at least one follow-up visit during their first six months after birth. Parents also reported whether their infants had become infected or had demonstrated COVID-19 symptoms.

    Based on blood samples from the infants, the researchers found that newborns with high antibody levels at birth also had greater protection from COVID-19 infection during their first six months. While infants of mothers who received two COVID-19 vaccine doses had a robust antibody response at birth, infants whose mothers had received an additional booster dose during pregnancy had both higher levels of antibodies at birth and greater protection from COVID-19 infection at their follow-up visits.

    While older children and adults should continue to follow guidance from the Centers for Disease Control and Prevention (CDC) to stay up-to-date on their COVID-19 vaccines and boosters, this study highlights how much maternal vaccination can benefit newborns too young to take advantage of the vaccine: During the course of this study, none of the infants examined required hospitalization for COVID-19. Researchers will continue to evaluate the data from the MOMI-Vax study for further insights concerning COVID-19 protection in infants.

    Source:

    Journal reference:

    Cardemil, C. V., et al. (2024). Maternal COVID-19 Vaccination and Prevention of Symptomatic Infection in Infants. Pediatrics. doi.org/10.1542/peds.2023-064252.

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  • Smoking, infection, and BMI found to significantly sway immune response, study shows

    Smoking, infection, and BMI found to significantly sway immune response, study shows

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    In a recent study published in the journal Nature, researchers explored the factors influencing cytokine release, a critical component of the host immunological response.

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emphasized the wide variation in immunological responses between populations, with age, sex, and genetic variables all playing vital roles. However, therapy and vaccine development often disregard immunological diversity. The Milieu Intérieur research project has contributed to understanding immune homeostasis by quantitatively evaluating the impacts of age, gender, cellular composition, and genetics on immune-related gene transcript levels and those of age, gender, smoking, and cytomegalovirus (CMV) infections on leukocyte distribution in blood. Further study might help us better understand the elements that influence immune responses and how they affect clinical outcomes.

    Study: Smoking changes adaptive immunity with persistent effects. Image Credit: NeydtStock / ShutterstockStudy: Smoking changes adaptive immunity with persistent effects. Image Credit: NeydtStock / Shutterstock

    About the study

    In the present study, researchers investigated environmental variables associated with cytokine responsiveness to immunological activation.

    The team measured the levels of several cytokines [C‐X‐C motif chemokine ligand 5 (CXCL5), colony-stimulating factor 2 (CSF2), interferon-gamma (IFNγ), interleukin-1 beta (IL-1β), IL-2, 6, 8, 10, 12p70, 13, 17, 23, and tumor necrosis factor (TNF)] after 22 hours of whole-blood stimulations with 11 immunological agonists for 1,000 Milieu Intérieur project donors and in an unstimulated (control) condition. They categorized the stimulations as microbial, viral, T-lymphocyte activated, and cytokines.

    Heat maps and principal component analyses (PCA) of 13 cytokine molecules investigated in 12 immunological stimulations revealed the individual cytokines generated by every independent condition. The team performed hierarchical clustering evaluations of log mean variations in cytokine levels to identify groups corresponding to stimulation types.

    The researchers compiled 136 environmental, socio-demographic, nutritional, and clinical variables from the digital case report forms and tested for their relationships with cytokines induced in every stimulation using likelihood ratio tests (LRTs) with age, experimental batch, and gender as covariates. They also investigated human leukocyte antigen (HLA) as a predictor of immune response variability, particularly in antigen-specific responses. The team investigated whether smoking-cytokine correlations continued when particular subsets of circulating immune cells were included in their models, as these cells are related to cytokine elevations. They evaluated the biological impact of smoking on cytokine production, calculating the effect sizes for the smoking variables in the linear models and assessing the influence of 326 soluble proteins in sera obtained from 400 donors.

    The researchers investigated whether epigenetic pathways contribute to the impact of smoking on adaptive immune responses. They analyzed deoxyribonucleic acid (DNA) methylation at more than 850,000 CpG sites and investigated whether the levels may explain the association between smoking and cytokine levels following SEB stimulation. The study was especially well-suited to identifying response protein quantitative trait loci (pQTLs) since it tested 5,699,237 high-quality imputed single nucleotide polymorphisms (SNPs) for relationships with the cytokines elicited by each stimulation.

    Results

    The team identified smoking, CMV latent infection, and body mass index (BMI) as the most significant drivers of cytokine response variability. Smoking impacts innate and adaptive immune responses, with the influence on innate responses diminishing after quitting and associated with serum carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) levels. However, the impact on adaptive responses lasts long after smoking cessation and is associated with epigenetic memory.

    The study highlighted eleven factors related to one or more cytokines in the immune stimulations, with BMI being the most prevalent. Smoking-related factors were related to interleukin-2 and interleukin-13 (adaptive immunity) in Staphylococcus aureus enterotoxin B superantigen (SEB), anti-cluster of differentiation 3 (anti-CD3) and anti-CD28 immune stimulations, and CXCL5 following Escherichia coli infections or innate immunological stimulations. The findings indicate that smoking causes inflammation and reduces immunity against bacterial infections.

    Cytomegalovirus latent infection was associated with TNF, CSF2, and IFNγ cytokines secreted by adaptive immune cells. BMI-related factors were related to CXCL5 following Bacillus Calmette-Guérin (BCG) immune stimulation, and interleukin-2 following SEB stimulation demonstrated obesity dysregulation. The team found no significant association between major histocompatibility complex (MH) class II, DQ beta 1, and HLA.DBQ1.1P, and IL-6 in the control condition.

    The study found 2,416 CpG locations related to smoking in the Milieu Intérieur sample, with 129 significantly associated with IL-2 in SEB stimulation. However, 11 CpGs abolished the relationship between smoking and IL-2 and IL-13. Current smokers had lower DNA methylation than non-smokers, but former smokers had an intermediate methylation level. The number of years smoked, total cigarettes smoked, and IL-2 levels in SEB stimulation were adversely linked with DNA methylation, although the number of years after smoking typically correlated positively.

    Overall, the study findings identified three novel factors, i.e., smoking status, CMV latent infection, and BMI, associated with variability in cytokine secretion following immunological stimulation. These characteristics may have clinical consequences for the risk of contracting infections, cancer, or autoimmune diseases. Smokers have a heightened inflammatory response after bacterial activation, which promptly decreases after quitting. However, the impacts on adaptive immunity last for years after stopping. The link between smoking and long-lived B and T cell subsets and DNA methylation offers a potential for long-term consequences in the adaptive response.

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  • A closer look reveals lasting impacts

    A closer look reveals lasting impacts

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    In a recent study published in the journal Pediatrics, a large team of scientists from the United States (U.S.) reviewed existing studies on post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC) to understand the long-term impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the pediatric population, including factors such as prevalence, clinical characteristics, risk factors, and underlying mechanisms.

    STATE-OF-THE-ART REVIEW – Postacute Sequelae of SARS-CoV-2 in Children. Image Credit: Donkeyworx / Shutterstock

    Background

    The global impact of the COVID-19 pandemic has touched multiple spheres of life, with economic and social consequences apart from the massive effect on the medical and healthcare fields. Studies have shown that the pandemic has disproportionately affected specific racial and socioeconomic groups. Furthermore, a significant portion of the population continues to struggle with persistent and debilitating aftereffects and symptoms of COVID-19, which has now been called PASC or long coronavirus disease (long COVID).

    Estimates indicate that the U.S. had approximately 20% pediatric cases of COVID-19, of which 10%–20% were thought to develop into PASC, which translates to roughly 5.8 million children in the country. The present study summarizes the current understanding of the epidemiology, prevalence, underlying mechanisms, clinical characteristics, and outcomes of PASC in the pediatric population.

    PASC epidemiology

    The review found no consensus on the prevalence of PASC among children, with a 4% to 62% prevalence being reported across studies. The researchers believe that differences in factors such as study design, follow-up durations, diagnostic criteria, and study population are responsible for the wide range of prevalence estimates. Furthermore, the broad symptoms, affecting multiple organ systems, and overlaps with existing comorbidities also make it challenging to diagnose PASC.

    There is also a paucity of studies examining the trajectory of PASC in the pediatric population, with very few studies having examined the progression of the disease beyond a year. Studies found that only 15% of asymptomatic SARS-CoV-2 infections in children progress to PASC, while 45% of the symptomatic infections were found to result in long-lasting sequelae.

    Furthermore, infections with variants before the emergence of Omicron were found to increase the risk of PASC. Increasing age, severity of the infection, higher body weight, chronic underlying medical conditions, and the organ systems affected during the acute SARS-CoV-2 infection were all found to be risk factors for developing PASC.

    While the contribution of environmental and psycho-social factors in the development and manifestation of PASC has not been well investigated, the scientists believe that the escalating food and housing insecurity, disruption of educational and health care resources, and lower family income could have increased the mental and physical health problems in children, lowering immunity, and exacerbating existing illnesses.

    PASC in children

    Based on existing information, the team formulated a conceptual model for PASC in the pediatric population. They defined PASC in children as a heterogeneous group of symptoms occurring after a SARS-CoV-2 infection, consisting of persistent COVID-19 symptoms such as cough, dyspnea, fatigue, headaches, anosmia, ageusia, and chronic pain. Furthermore, exacerbation of existing conditions such as increased cough in children with asthma, deterioration of neurodevelopmental and mental health conditions, and diabetic ketoacidosis in pediatric diabetes cases are also thought to be a part of PASC.

    The review emphasizes the need to give special consideration to understanding the development of PASC in children at a higher risk of SARS-CoV-2 infections due to existing comorbidities and medical conditions. The researchers also discussed the potential development of de-novo post-acute conditions and the onset of autoimmune disorders. Studies have already reported multisystem inflammatory syndrome in children (MIS-C) as being one of the prevalent complications of COVID-19 in children.

    The review also provided a comprehensive summary of the wide range of manifestations and symptoms of PASC, including constitutional symptoms such as persistent fatigue, post-exertional malaise, brain fog or difficulty concentrating, depressive symptoms, and somnolence. The researchers also discussed the respiratory, cardiac, neurological, olfactory, gastrointestinal, mental health, musculoskeletal, dermatological, and inflammatory or hematological manifestations of PASC in detail.

    Furthermore, the study also examined the role of PASC in exacerbating underlying conditions in children, such as asthma, fibromyalgia, and connective tissue disorders, as well as post-infectious conditions such as MIS-C and de-novo conditions such as diabetes, autoimmune disorders, and neurological problems that could potentially develop during PASC.

    Conclusions

    To summarize, the review examined studies investigating the long-term consequences of SARS-CoV-2 infections in children and presented a comprehensive picture of the current understanding of PASC in children. The findings indicate that while the severity and prevalence of COVID-19 in the pediatric population were not as high as in adults, PASC does entail severe and long-lasting consequences, including the development of new autoimmune conditions and diabetes. These results highlight the need to form initiatives to further understand the susceptibility of children with underlying medical conditions to SARS-CoV-2 infections.

    Journal reference:

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  • AI’s ability to detect COVID-19 from coughs faces real-world challenges

    AI’s ability to detect COVID-19 from coughs faces real-world challenges

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    A recent Nature Machine Intelligence study investigated the efficacy of audio-based artificial intelligence (AI) classifiers in predicting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection status. SARS-CoV-2 is the causal organism of the coronavirus disease 2019 (COVID-19) pandemic.

    Study: Audio-based AI classifiers show no evidence of improved COVID-19 screening over simple symptoms checkers. Image Credit: Aliaksandra Post / ShutterstockStudy: Audio-based AI classifiers show no evidence of improved COVID-19 screening over simple symptoms checkers. Image Credit: Aliaksandra Post / Shutterstock

    Background

    Since SARS-CoV-2 infection could cause both symptomatic and asymptomatic manifestations, it is important to develop accurate tests to avoid general population quarantine. Previous studies have revealed that AI-based classifiers trained with respiratory audio data could identify SARS-CoV-2 status. 

    Although these studies indicated the effectiveness of AI-based classifiers, many challenges surfaced while applying them in real-world settings. Some factors that withheld AI-based classifier applications were sampling biases, unvalidated data on participants’ COVID-19 status, and delay between infection and audio recording. It is imperative to determine whether the audio biomarkers of COVID-19 are unique to SARS-CoV-2 infection or are inappropriate confounding signals.

    About the Study

    The current study focussed on determining whether audio-based classifiers can be accurately used for COVID-19 screening. A large-scale polymerase chain reaction (PCR) dataset linked to audio-based COVID-19 screening (ABCS) was used. For this study, participants of the Real-time Assessment of Community Transmission (REACT) program and the National Health Service (NHS) Test-and-Trace (T+T) service were invited. All relevant demographic data was extracted from T+T/REACT records.

    Participants were asked to complete survey questions and record four audio clips. For audio recordings, they were asked to read a specific sentence, followed by three successive exhalations, making a “ha” sound. Furthermore, the participants were asked to record forced coughs once and three times in succession. All recordings were documented in .wav format. The quality of the audio recordings was assessed, and 5,157 records were removed for quality-related issues.

    Human figures represent study participants and their corresponding COVID-19 infection status, with the different colours portraying different demographic or symptomatic features. When participants are randomly split into training and test sets, the randomized split models perform well at COVID-19 detection, achieving AUCs in excess of 0.8; however, matched test set performance is seen to drop to estimated AUC between 0.60 and 0.65, with an AUC of 0.5 representing random classification. Inflated classification performance is also seen in engineered out of distribution test sets such as: the designed test set, in which a select set of demographic groups appear solely in the testing set, and the longitudinal test set, in which there is no overlap in the time of submission between train and test instances. The 95% confidence intervals calculated via the normal approximation method are shown, along with the corresponding n numbers of the train and test sets.Human figures represent study participants and their corresponding COVID-19 infection status, with the different colours portraying different demographic or symptomatic features. When participants are randomly split into training and test sets, the randomized split models perform well at COVID-19 detection, achieving AUCs in excess of 0.8; however, matched test set performance is seen to drop to estimated AUC between 0.60 and 0.65, with an AUC of 0.5 representing random classification. Inflated classification performance is also seen in engineered out of distribution test sets such as: the designed test set, in which a select set of demographic groups appear solely in the testing set, and the longitudinal test set, in which there is no overlap in the time of submission between train and test instances. The 95% confidence intervals calculated via the normal approximation method are shown, along with the corresponding n numbers of the train and test sets.

    Study Findings

    In this study, a respiratory acoustic dataset of 67,842 individuals was collected. Among them, 23,514 individuals tested positive for COVID-19. All data were linked with PCR test results. It must be noted that the most significant number of COVID-19-negative participants were recruited from six REACT rounds compared to the T+T channel.

    The dataset considered in this study exhibited promising coverage across England. No significant association between geographical location and COVID-19 status was noted. The highest level of COVID-19 imbalance was found in Cornwall. A previous study indicated recruitment bias in ABCS, particularly linked with age, language, and gender, in both training data and test sets. Despite this bias, the training dataset was balanced in accordance with age and gender across COVID-positive and COVID-negative subgroups. 

    Consistent with previous studies, the unadjusted analysis conducted in this study exhibited that AI classifiers can predict COVID-19 status with high accuracy. However, when measured confounders were matched, a weak performance of AI classifiers in detecting SARS-CoV-2 status was observed.

    Based on the findings, the current study proposed some guidelines to rectify recruitment bias’s effect for future studies. Some of the recommendations are listed below:

    1. Audio samples stored in repositories must include details of the study recruitment criteria. In addition, relevant information about the individuals, including their gender, age, time of COVID-19 test, SARS-CoV-2 symptoms, and locations, must be documented along with the audio recording.
    2. All confounding factors must be identified and matched to help control recruitment bias.
    3. Experimental design must be developed, keeping the possible bias in mind. In most cases, data matching leads to a reduction in sample size. Observational studies recruit participants focusing on the maximized possibility of matching measured confounders.
    4. The predictive values of the classifiers must be compared with standard protocol findings.
    5. AI classifiers’ predictive accuracy must be assessed. However, the predictive accuracy, sensitivity, and specificity vary depending on the targeted population.
    6. The classifiers’ utility must be assessed for each testing outcome.
    7. The replication study must be conducted in randomized cohorts. Furthermore, pilot studies must be conducted in real-world settings based on domain-specific utility.

    Conclusions

    The current study has come with limitations that include the possibility of potential unmeasured confounders across REACT and T+T recruitment channels. For instance, PCR testing for COVID-19 was performed several days after self-screening of symptoms. In contrast, PCR tests in REACT were conducted on a pre-determined date, irrespective of the onset of symptoms. Although the majority of confounders were matched, there is a possibility of the presence of residual predictive variation.

    Despite the limitations, this study highlighted the need to develop accurate machine-learning evaluation procedures to obtain unbiased outputs. Furthermore, it revealed that confounding factors are hard to detect and control across many AI applications.

    Journal reference:

    • Coppock, H. et al. (2024) Audio-based AI classifiers show no evidence of improved COVID-19 screening over simple symptoms checkers. Nature Machine Intelligence. 1-14. DOI: 10.1038/s42256-023-00773-8, https://www.nature.com/articles/s42256-023-00773-8

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  • Hunters key to early detection of zoonotic diseases, study finds

    Hunters key to early detection of zoonotic diseases, study finds

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    To prevent future health crises, monitoring the emergence of zoonotic diseases in wild meat value chains is essential. In this regard, the role of community hunters is crucial, as they can report early signs of possible disease in game animals.

    Study: An experimental game to assess hunter’s participation in zoonotic diseases surveillance. Image Credit: Virrage Images / Shutterstock.com

    Background

    Since the mid-twentieth century, zoonotic diseases have caused 60% of emerging disease events. More recently, wildlife has been suspected to be the original reservoir of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the coronavirus disease 2019 (COVID-19) pandemic.

    Wild animal hunting and trade facilitate human-wildlife interactions and spillover events. Community-based surveillance can provide early warning and aid in limiting the spread of a zoonotic disease. However, research has shown that local communities perceive the risk of disease transmission from animals to humans differently.

    About the study

    In a recent study published in BMC Public Health, researchers designed an experimental game (EG) to better understand the response of community hunters when encountered with signs of zoonotic diseases in game animals.

    EGs provide important insights into the decision-making of a group of individuals. These “players” are confronted with hypothetical scenarios and are asked to choose among different options. Observations from EGs are compared to game theoretical predictions, which assume players to be rational utility-maximizers.

    In the forested area of Gabon in central Africa, an EG was developed and tested that mimicked the implementation of a community-based surveillance system. Voluntary reports of hunters were used to monitor zoonotic diseases in wildlife.

    Both subsistence and commercial hunters were included in the EG. The key aim was to identify the characteristics of hunters, surveillance, and epidemiological processes that could influence their probability of participating in wildlife disease surveillance.

    A total of 88 hunters were divided into nine groups, each comprising five to 13 players. Over 21 rounds of the EG were performed, each of which involved a hunting trip simulation where the payers were likely to capture a wild animal with clinical signs of zoonotic disease.

    When signs of the zoonotic disease were visible, the participants were asked to report or sell/consume the animal. Reporting meant lower hunting revenue but also a lower probability of the spread of a zoonotic disease, which could benefit the entire community.

    Key findings

    A false alert, defined as a flagged case not caused by a zoonotic disease, led to reduced case reports in the subsequent round. Concerning hunter characteristics, those who engaged in agricultural activity, in addition to hunting, flagged suspected cases more often than their counterparts. The number of potential case reports rose with each round, thus suggesting a greater inclination to report throughout the game.

    In the game-theoretic model, participation in surveillance was associated with positive externalities. Relevant information benefits the community as a whole; however, it comes at a cost for the reporting player, which could lead to sub-optimal participation in reporting. The game sessions corroborated this theoretical hypothesis.

    The subsequent reduction in reports followed by a false report was due to false reports reducing the anticipated benefit of reporting. Prior research has shown that from a societal point of view, false alerts are acceptable as long their costs do not exceed the benefits of accurate disease detection.

    In the future, community engagement programs should highlight the utility of periodic false alerts. This will help maintain regular surveillance and its proper functioning in the event a zoonotic disease emerges.

    Players engaging in agricultural work were more likely to flag suspected cases of zoonotic disease than their counterparts. For these hunters, agriculture often accounts for a significant portion of household income, thereby reducing their reliance on hunting revenue to support their families. Thus, economic dependence on wild meat likely governs the decision to participate in surveillance systems.

    Conclusions

    The current study highlights the usefulness of EGs in enhancing our understanding of hunters’ willingness to participate in zoonotic disease surveillance. Extending the game to include all potential actors of surveillance along the wild meat value chains could provide helpful information to better manage the risks stemming from zoonotic diseases.

    Journal reference:

    • Pouliquen, A., Mapeyi, G. A. B., Vanthomme, G., et al. (2024) An experimental game to assess hunter’s participation in zoonotic diseases surveillance. BMC Public Health 24(342). doi:10.1186/s12889-024-17696-7

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  • Study reveals high insomnia rates in non-hospitalized COVID-19 survivors

    Study reveals high insomnia rates in non-hospitalized COVID-19 survivors

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    In a recent study published in Frontiers in Public Health, researchers investigated insomnia prevalence and its association with anxiety and depression in the non-hospitalized coronavirus disease 2019 (COVID-19)-recovered community.

    Study: Sleep quality among non-hospitalized COVID-19 survivors: a national cross-sectional study. Image Credit: Stock-Asso/Shutterstock.com
    Study: Sleep quality among non-hospitalized COVID-19 survivors: a national cross-sectional study. Image Credit: Stock-Asso/Shutterstock.com

    Background

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has afflicted millions globally since late 2019, with most cases resolved by mid-2023. Common symptoms include coughing, weariness, fever, dyspnea, musculoskeletal issues, gastrointestinal complaints, anosmia, dysgeusia, and vertigo. Post-infection and long-term physical and psychological difficulties are serious public health concerns.

    Insomnia is a prevalent complaint, particularly among hospitalized COVID-19 patients. High-risk variables include being female, younger, and more educated, as well as having anxiety, depression, or post-traumatic stress disorder. Poor mental health is associated with insufficient sleep, and chronic disorders such as obstructive sleep apnea (OSA) can affect glycemic control, neurocognitive impairment, and aberrant functional pulmonary alterations.

    About the study

    In the current nationwide cross-sectional study, researchers investigated insomnia prevalence among COVID-19 survivors with no or moderate symptoms who did not require hospitalization throughout the recovery period (six months) and discovered relevant variables.

    Between June and September 2022, the team conducted a web-based survey among 1,056 COVID-19-recovered individuals who recovered within six months of acute SARS-CoV-2 infection and did not need hospitalization. They used the Depression Anxiety and Stress Scale-14 (DASS-14) and the Insomnia Severity Index (ISI). They obtained data on demographics such as age, marital status, sex, educational attainment, occupation, employment status, and comorbidities.

    The team asked the respondents to rate their SARS-CoV-2 infection severity and duration (days from the initial SARS-CoV-2-positive to the initial SARS-CoV-2-negative report). In addition, the respondents compared their sleep quality, sleep initiation, and total sleep duration in the previous two weeks with the time before confirming the SARS-CoV-2 infection.

    The team used multivariate logistic regressions to determine odds ratios (OR) for the relationships between anxiety and depression scores and insomnia levels among the survey respondents. They included adult COVID-19 survivors (who recovered as confirmed using polymerase chain reaction (PCR) within six months and did not require COVID-19-associated hospitalization) in Vietnam’s general population. They excluded individuals diagnosed with insomnia or psychological disorders before the study.

    Results

    The study included 1,056 individuals, with the majority being married (64%), female (69%), and having attended university (69%). After the SARS-CoV-2 infection, almost a third of respondents reported shorter sleep duration, worsened sleep quality, and more difficulties falling asleep, and half of them reported more nocturnal awakenings. Insomnia prevalence was 76%, with 23% of patients reporting severe insomnia.

    Individuals with anxiety (OR, 3.9) or depression (OR, 3.5) had a significantly increased risk of having insomnia. Other characteristics that increased the likelihood of sleeplessness included higher educational attainment and pre-existing medical conditions, but COVID-19 duration and symptoms had no significant relationship.

    Individuals who were divorced or widowed, female, had postgraduate education, were not actively employed, or suffered from chronic medical conditions had higher mean ISI ratings than their peers. Concerning COVID-19, 92% of infected individuals experienced symptoms (mean, 11 weeks). Although these symptomatic individuals showed higher ISI scores (15.2), there was no significant difference compared to individuals without symptoms.

    The mean scores for anxiety and depression were 7.6 and 6.4, respectively, with 439 (42%) and 291 (28%) individuals reporting relevant symptoms, respectively. Individuals with symptoms of anxiety (18.7) and depression (19.1) scored significantly higher on the ISI compared to those without (12.4 and 13.5, respectively). Participants experiencing insomnia scored higher on anxiety (9.2) and depression (7.8) than the overall group mean.

    In univariate analysis, those who were wedded and had a university degree were significantly less likely to experience insomnia than single and formally-educated individuals. Students were significantly more likely to experience insomnia compared to healthcare workers. Individuals with a history of chronic medical conditions were significantly more likely to suffer from insomnia following COVID-19 compared to healthy individuals. After controlling for variables, healthcare professionals had a significantly increased likelihood of insomnia (OR, 1.6) than workers in other professions; however, there were no differences compared to those who did not work or were students.

    Conclusion

    Overall, the study findings highlighted insomnia prevalence among COVID-19 survivors, with more than 75% reporting it. This percentage is much higher than that of the general population (10% to 20%) and hospitalized survivors (12% to 47%). Individuals with chronic medical conditions are more likely to suffer from insomnia, which is underreported. Public health researchers should anticipate a greater frequency of insomnia and sleep disorders in this group, which can last for one-third of healed patients up to one year after infection.

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