Systems analysis of human innate immunity in COVID-19.

Recent developments in sequencing technologies, the computer and data sciences, as well as increasingly high-throughput immunological measurements have made it possible to derive holistic views on pathophysiological processes of disease and treatment effects directly in humans. We and others have illustrated that incredibly predictive data for immune cell function can be generated by single cell multi-omics (SCMO) technologies and that these technologies are perfectly suited to dissect pathophysiological processes in a new disease such as COVID-19, triggered by SARS-CoV-2 infection. Systems level interrogation not only revealed the different disease endotypes, highlighted the differential dynamics in context of disease severity, and pointed towards global immune deviation across the different arms of the immune system, but was already instrumental to better define long COVID phenotypes, suggest promising biomarkers for disease and therapy outcome predictions and explains treatment responses for the widely used corticosteroids. As we identified SCMO to be the most informative technologies in the vest to better understand COVID-19, we propose to routinely include such single cell level analysis in all future clinical trials and cohorts addressing diseases with an immunological component.

Neurological complications caused by SARS-CoV-2.

SUMMARYSARS-CoV-2 can not only cause respiratory symptoms but also lead to neurological complications. Research has shown that more than 30% of SARS-CoV-2 patients present neurologic symptoms during COVID-19 (A. Pezzini and A. Padovani, Nat Rev Neurol 16:636-644, 2020, https://doi.org/10.1038/s41582-020-0398-3). Increasing evidence suggests that SARS-CoV-2 can invade both the central nervous system (CNS) (M.S. Xydakis, M.W. Albers, E.H. Holbrook, et al. Lancet Neurol 20: 753-761, 2021 https://doi.org/10.1016/S1474-4422(21)00182-4 ) and the peripheral nervous system (PNS) (M.N. Soares, M. Eggelbusch, E. Naddaf, et al. J Cachexia Sarcopenia Muscle 13:11-22, 2022, https://doi.org/10.1002/jcsm.12896), resulting in a variety of neurological disorders. This review summarized the CNS complications caused by SARS-CoV-2 infection, including encephalopathy, neurodegenerative diseases, and delirium. Additionally, some PNS disorders such as skeletal muscle damage and inflammation, anosmia, smell or taste impairment, myasthenia gravis, Guillain-Barré syndrome, ICU-acquired weakness, and post-acute sequelae of COVID-19 were described. Furthermore, the mechanisms underlying SARS-CoV-2-induced neurological disorders were also discussed, including entering the brain through retrograde neuronal or hematogenous routes, disrupting the normal function of the CNS through cytokine storms, inducing cerebral ischemia or hypoxia, thus leading to neurological complications. Moreover, an overview of long-COVID-19 symptoms is provided, along with some recommendations for care and therapeutic approaches of COVID-19 patients experiencing neurological complications.

Single-Cell RNA Sequencing Reveals Alterations in Patient Immune Cells with Pulmonary Long COVID-19 Complications.

Since the emergence of the COVID-19 pandemic, the effects of SARS-CoV-2 have been extensively researched. While much is already known about the acute phase of the infection, increasing attention has turned to the prolonged symptoms experienced by a subset of individuals, commonly referred to as long COVID-19 patients. This study aims to delve deeper into the immune landscape of patients with prolonged symptoms by implementing single-cell mRNA analysis. A 71-year-old COVID-19 patient presenting with persistent viral pneumonia was recruited, and peripheral blood samples were taken at 3 and 2 years post-acute infection onset. Patients and control peripheral blood mononuclear cells (PBMCs) were isolated and single-cell sequenced. Immune cell population identification was carried out using the ScType script. Three months post-COVID-19 patients' PBMCs contained a significantly larger immature neutrophil population compared to 2-year and control samples. However, the neutrophil balance shifted towards a more mature profile after 18 months. In addition, a notable increase in the CD8+ NKT-like cells could be observed in the 3-month patient sample as compared to the later one and control. The subsequent change in these cell populations over time may be an indicator of an ongoing failure to clear the SARS-CoV-2 infection and, thus, lead to chronic COVID-19 complications.

Prolonged platelet hyperactivity after COVID-19 infection.

Platelet hyperactivity often occurs in patients with coronavirus disease 2019 (COVID-19). However, it remains unclear how long platelet hyperactivity lasts after the acute phase, owing to a lack of follow-up studies. To elucidate the course of platelet hyperactivity, we serially measured platelet activity in patients with COVID-19 up to 40 days after hospital admission using an easily assessable haematology analyser that semi-quantitates platelet clumps on a scattergram. Our results showed that platelet hyperactivity persisted for at least 40 days even after acute inflammation subsided in most patients with COVID-19, regardless of disease severity. Persistent platelet hyperactivity may contribute to thromboembolic complications in post-COVID-19 patients.

Bioinformatic analysis predicts the regulatory function of noncoding SNPs associated with Long COVID-19 syndrome.

Long or Post COVID-19 is a condition of collected symptoms persisted after recovery from COVID-19. Host genetic factors play a crucial role in developing Long COVID-19, and GWAS studies identified several SNPs/genes in various ethnic populations. In African-American population two SNPS, rs10999901 (C>T, p = 3.6E-08, OR = 1.39, MAF-0,27, GRCH38, chr10:71584799 bp) and rs1868001 (G>A, p = 6.7E-09, OR = 1.40, MAF-0.46, GRCH38, chr10:71587815 bp) and in Hispanic population, rs3759084 (A>C, p = 9.7E-09, OR = 1.56, MAF-0.17, chr12: 81,110,156 bp) are strongly associated with Long COVID-19. All these three SNPs reside in noncoding regions implying their regulatory function in the genome. In silico dissection suggests that rs10999901 and rs1868001 physically interact with the CDH23 and C10orf105 genes. Both SNPs act as distant enhancers and bind with several transcription factors (TFs). Further, rs10999901 SNP is a CpG that is methylated in CD4++ T cells and monocytes and loses its methylation due to transition from C>T. rs3759084 is located in the promoter (- 687 bp) of MYF5, acts as a distant enhancer, and physically interacts with PTPRQ. These results offer plausible explanations for their association and provide the basis for experiments to dissect the development of symptoms of Long COVID-19.

Pathogenesis of Pulmonary Long COVID-19.

COVID-19 is characterized by an acute respiratory illness that, in some patients, progresses to respiratory failure, largely demonstrating a pattern of acute respiratory distress syndrome. Excluding fatal cases, the outcome of this severe illness ranges from complete resolution to persistent respiratory dysfunction. This subacute-to-chronic respiratory illness has different manifestations and is collectively termed as "long COVID." The pathogenesis of organ dysfunction in acute injury stems from exaggerated innate immune response, complement activation, and monocyte influx, with a shift toward an organ injury state with abnormalities in cellular maturation. Although the increased rate of thrombosis observed in acute COVID-19 does not appear to persist, interestingly, ongoing symptomatic COVID-19 and post-COVID pathogeneses appear to reflect the persistence of immune and cellular disturbances triggered by the acute and subacute periods.

High throughput spatial immune mapping reveals an innate immune scar in post-COVID-19 brains.

The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine learning methods on brains from initial COVID-19 survivors to identify the biological correlate associated with previous SARS-CoV-2 challenge. Compared to healthy controls, individuals with post-COVID-19 revealed a high percentage of TMEM119+P2RY12+CD68+Iba1+HLA-DR+CD11c+SCAMP2+ microglia assembled in prototypical cellular nodules. In contrast to acute SARS-CoV-2 cases, the frequency of CD8+ parenchymal T cells was reduced, suggesting an immune shift toward innate immune activation that may contribute to neurological alterations in post-COVID-19 patients.

Dysregulated platelet function in patients with postacute sequelae of COVID-19.

BACKGROUND: Postacute sequelae of COVID-19 (PASC), also referred to as "Long COVID", sometimes follows COVID-19, a disease caused by SARS-CoV-2. Although SARS-CoV-2 is well known to promote a prothrombotic state, less is known about the thrombosis risk in PASC. Our objective was to evaluate platelet function and thrombotic potential in patients following recovery from SARS-CoV-2, but with clear symptoms of patients with PASC. METHODS: patients with PASC and matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by light transmission aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under shear stress conditions. RESULTS: A mild increase in platelet aggregation in patients with PASC through the thromboxane receptor was observed, and platelet activation through the glycoprotein VI (GPVI) receptor was decreased in patients with PASC compared to age- and sex-matched healthy controls. Thrombosis under shear conditions as well as Factor Xa activity were reduced in patients with PASC. Plasma from patients with PASC was an extremely potent activator of washed, healthy platelets - a phenomenon not observed when stimulating healthy platelets after incubation with plasma from healthy individuals. CONCLUSIONS: patients with PASC show dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating molecule that promotes thrombosis. A hitherto undescribed protective response appears to exist in patients with PASC to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.

Impact of SARS-CoV-2 viral load on restrictive spirometry patterns in mild COVID-19 recovered middle-aged individuals: a six-month prospective study.

BACKGROUND: Long term respiratory complications of Corona Virus Disease-2019 (COVID-19) are of great concern. Many studies have reported altered respiratory patterns in COVID-19 recovered individuals and most of them were from severe to critically ill patients. The association of viral load at the time of infection with symptoms of long COVID-19 specifically on pulmonary functions after months of recovery is still not known. This study was aimed to assess the impact of SARS-CoV-2 viral load during mild-moderate COVID-19 disease on pulmonary functions in middle-aged population after 6-8 months of acute infection. METHODS: This study included 300 (102 healthy controls and 198 COVID-19 recovered) individuals between age 30-60 of either gender. Mild-moderate COVID-19 recovered individuals were recruited between a period of 6-8 months post-acute infection. Spirometry was performed with MIR-Spirolab-III. The association of spirometry pattern was compared with SARS-CoV-2 viral loads during acute infection. RESULTS: We observed up to 70% of the participants presented with either shortness of breath (11.5%), body aches (23.5%), recurrent cough (4.4%), recurrent respiratory infections (9.5%) and/or fatigue (33.3%) at follow up. In our study, 35.5% of COVID-19 recovered individuals had abnormal respiratory patterns (33.5% had restrictive and 2% had obstructive patterns). Viral load ≤ 20 CT value was associated with restrictive respiratory patterns (p = 0.004). No association was found between viral load and disease severity (p = 0.23). CONCLUSION: In this study, we found one third of mild-moderate COVID-19 recovered individuals have restrictive respiratory patterns after 6-8 months of recovery. These findings had a strong association with SARS-CoV-2 viral loads during acute infection which has been reported for the first time in our study. Studying the relationship between viral load and pulmonary functions can contribute to identifying potential risk factors for long COVID and developing preventive measures to mitigate the long-term impact on lung health. CLINICAL TRIAL NUMBER: Not applicable.

Unveiling Post-COVID-19 syndrome: incidence, biomarkers, and clinical phenotypes in a Thai population.

BACKGROUND: Post-COVID- 19 syndrome (PCS) significantly impacts the quality of life of survivors. There is, however, a lack of a standardized approach to PCS diagnosis and management. Our bidirectional cohort study aimed to estimate PCS incidence, identify risk factors and biomarkers, and classify clinical phenotypes for enhanced management to improve patient outcomes. METHODS: A bidirectional prospective cohort study was conducted at five medical sites in Hatyai district in Songkhla Province, Thailand. Participants were randomly selected from among the survivors of COVID-19 aged≥18 years between May 15, 2022, and January 31, 2023. The selected participants underwent a scheduled outpatient visit for symptom and health assessments 12 to 16 weeks after the acute onset of infection, during which PCS was diagnosed and blood samples were collected for hematological, inflammatory, and serological tests. PCS was defined according to the World Health Organization criteria. Univariate and multiple logistic regression analyses were used to identify biomarkers associated with PCS. Moreover, three clustering methods (agglomerative hierarchical, divisive hierarchical, and K-means clustering) were applied, and internal validation metrics were used to determine clustering and similarities in phenotypes. FINDINGS: A total of 300 survivors were enrolled in the study, 47% of whom developed PCS according to the World Health Organization (WHO) definition. In the sampled cohort, 66.3% were females, and 79.4% of them developed PCS (as compared to 54.7% of males, p-value <0.001). Comorbidities were present in 19% (57/300) of all patients, with 11% (18/159) in the group without PCS and 27.7% (39/141) in the group with PCS. The incidence of PCS varied depending on the criteria used and reached 13% when a quality of life indicator was added to the WHO definition. Common PCS symptoms were hair loss (22%) and fatigue (21%), while mental health symptoms were less frequent (insomnia 3%, depression 3%, anxiety 2%). According to our univariate analysis, we found significantly lower hematocrit and IgG levels and greater ALP levels in PCS patients than in patients who did not develop PCS (p-value < 0.05). According to our multivariable analysis, adjusted ALP levels remained a significant predictor of PCS (OR 1.02, p-value= 0.005). Clustering analysis revealed four groups characterized by severe clinical symptoms and mental health concerns (Cluster 1, 4%), moderate physical symptoms with predominant mental health issues (Cluster 2, 9%), moderate mental health issues with predominant physical symptoms (Cluster 3, 14%), and mild to no PCS (Cluster 4, 77%). The quality of life and ALP levels varied across the clusters. INTERPRETATION: This study challenges the prevailing diagnostic criteria for PCS, emphasizing the need for a holistic approach that considers quality of life. The identification of ALP as a biomarker associated with PCS suggests that its monitoring could be used for early detection of the onset of PCS. Cluster analysis revealed four distinct clinical phenotypes characterized by different clinical symptoms and mental health concerns that 'exhibited varying impacts on quality of life. This finding suggested that accounting for the reduced quality of life in the definition of PCS could enhance its diagnosis and management and that moving toward personalized interventions could both improve patient outcomes and help reduce medicalization and optimally target the available resources. FUNDING: The research publication received funding support from Medical Council of Thailand (Police General Dr. Jongjate Aojanepong Foundation), Hatyai Hospital Charity and Wellcome Trust.

Barriers and facilitators of healthcare access for long COVID-19 patients in a universal healthcare system: qualitative evidence from Austria.

BACKGROUND: Long COVID-19 challenges health and social systems globally. International research finds major inequalities in prevalence and healthcare utilization as patients describe difficulties with accessing health care. In order to improve long-term outcomes it is vital to understand any underlying access barriers, for which relevant evidence on long COVID-19 is thus far lacking in a universal healthcare system like Austria. This study aims to comprehensively identify access barriers and facilitators faced by long COVID-19 patients in Austria and explore potential socioeconomic and demographic drivers in health and social care access. METHODS: Applying an exploratory qualitative approach, we conducted semi-structured interviews with 15 experts including medical professionals and senior health officials as well as focus groups with 18 patients with confirmed long COVID-19 diagnosis reflecting varying participant characteristics (age, gender, urbanicity, occupation, education, insurance status) (July-Nov 2023). Data were analysed following a thematic framework approach, drawing on a comprehensive 'access to health care' model. RESULTS: Based on expert and patient experiences, several access barriers and facilitators emerged along all dimensions of the model. Main themes included scepticism and stigma by medical professionals, difficulties in finding knowledgeable doctors, limited specialist capacities in the ambulatory care sector, long waiting times for specialist care, and limited statutory health insurance coverage of treatments resulting in high out-of-pocket payments. Patients experienced constant self-organization of their patient pathway as stressful, emphasizing the need for multidisciplinary care and centralized coordination. Facilitators included supportive social environments, telemedicine, and informal information provided by a nationwide patient-led support group. Differences in patient experiences emerged, among others, as women and younger patients faced gender- and age-based stigmatization. Complementary health insurance reduced the financial strain, however, did not ease capacity constraints, which were particularly challenging for those living in rural areas. CONCLUSIONS: The findings of this study indicate a call for action to improve the long COVID-19 situation in Austria by empowering both providers and patients via increased information offerings, strengthened interdisciplinary treatment structures and telemedicine offerings as well as research funding. Our insights on potentially relevant socioeconomic and demographic drivers in access barriers lay the necessary foundation for future quantitative inequality research.

COVID-19 after 2 Years from Hospital Discharge: A Pulmonary Function and Chest Computed Tomography Follow-Up Study.

INTRODUCTION: Serial follow-up with pulmonary function testing (PFT) and chest computed tomography (CT) after severe COVID-19 are recommended. As a result, many longitudinal studies have been published on COVID-19 of different grade of severity up to 1-year follow-up. Therefore, we aimed at a long-term observational study throughout 2 years after severe COVID-19. METHODS: Severe COVID-19 patients were consecutively recruited after hospital discharge between March and June 2020 and prospectively followed up for 24 months, with mMRC dyspnea scale and PFT at 6, 12, and 24 months. Chest CT was performed when clinically indicated. RESULTS: One hundred one patients enrolled completed the observational study. At 24 months, those with reduced total lung capacity (TLC) were 16%, associated with fibrotic ground glass opacity (GGO) and mMRC score >1, respectively, in 75% and 69% of them. At 24 months, those with a reduced diffusing capacity of the lung for CO were 41%, associated with fibrotic GGO and mMRC score >1, respectively, in 53% and 22% of them. CONCLUSION: Two years after hospitalization for severe COVID-19, a non-negligible number of patients still suffer from "long COVID" due to respiratory damage.

Epidemiological and clinical characteristics of long COVID-19 among Iranians: A community-based study in southern Iran.

BACKGROUND: The study aimed to evaluate the prevalence and pattern of long COVID-19 (LC) symptoms among individuals who had contracted COVID-19, to calculate the incidence of LC, and to provide insights into risk factors associated with developing LC in this population. METHODS: This population-based cross-sectional survey was conducted in Fars province in 2023. Adult participants with a history of COVID-19 were recruited using a cluster random sampling method, alongside a control group with similar characteristics through the same methodology. Data were collected through in-person interviews using two researcher-developed data collection forms focused on demographic and clinical information. RESULTS: A total of 2010 participants, comprising 1561 (77.7%) and 449 (22.3%) individuals with and without a previous history of COVID-19 were included. Among those with COVID-19 history, the prevalence of experiencing any symptoms was 93.7% (95% CI of 92.3%-94.8%) during the disease acute phase and 36.4% (95% CI of 34.0%-38.8%) after recovery. The incidence of symptoms specifically related to COVID-19, calculated by comparing the symptom rates between participants with and without a history of COVID-19, was found to be 13%. Factors such as older age, previous hospitalization for COVID-19, presence of cardiovascular disease, and use of steroids/chemotherapy were associated with LC symptoms. CONCLUSIONS: Our investigation sheds light on long-term aspects of COVID-19, demonstrating a significant prevalence of LC with diverse manifestations. It also underscores the importance of establishing standardized criteria and control groups in research on LC to address challenges related to heterogeneity and potential overestimation of symptoms.

Cardiovascular diseases as risk factors of post-COVID syndrome: a systematic review.

BACKGROUND: A growing proportion of people experience incomplete recovery months after contracting coronavirus disease 2019 (COVID-19). These COVID-19 survivors develop a condition known as post-COVID syndrome (PCS), where COVID-19 symptoms persist for > 12 weeks after acute infection. Limited studies have investigated PCS risk factors that notably include pre-existing cardiovascular diseases (CVD), which should be examined considering the most recent PCS data. This review aims to identify CVD as a risk factor for PCS development in COVID-19 survivors. METHODS: Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist, systematic literature searches were performed in the PubMed, Scopus, and Web of Science databases from the earliest date available to June 2023. Data from observational studies in English that described the association between CVD and PCS in adults (≥ 18 years old) were included. A minimum of two authors independently performed the screening, study selection, data extraction, data synthesis, and quality assessment (Newcastle-Ottawa Scale). The protocol of this review was registered under PROSPERO (ID: CRD42023440834). RESULTS: In total, 594 studies were screened after duplicates and non-original articles had been removed. Of the 11 included studies, CVD including hypertension (six studies), heart failure (three studies), and others (two studies) were significantly associated with PCS development with different factors considered. The included studies were of moderate to high methodological quality. CONCLUSION: Our review highlighted that COVID-19 survivors with pre-existing CVD have a significantly greater risk of developing PCS symptomology than survivors without pre-existing CVD. As heart failure, hypertension and other CVD are associated with a higher risk of developing PCS, comprehensive screening and thorough examinations are essential to minimise the impact of PCS and improve patients' disease progression.

Oculomotor Behaviour in Individuals with Long COVID-19.

OBJECTIVE: To determine, the impact of long COVID-19 on oculomotor behaviour. DESIGN: A case-control study. SETTING: Spanish Association of Persistent COVID. PARTICIPANT: Participants were 75 cases (64 women, 11 men, mean age 46.4 years ±8.9) and 42 controls (22 women, 20 men, mean age 53.5 years ±13.13). INTERVENTION: An eye-tracking test based on visual search paradigm and the Adult Developmental Eye Movement Test were used to evaluate the participants. MAIN MEASURES: The primary outcomes in the Adult Developmental Eye Movement Test were horizontal reading time, vertical reading time, and their ratio. And for the eye-tracking test the time to find the target, the duration, and the number of eye fixations. RESULTS: In cases and controls, eye movement test results were horizontal(Hadj) reading time 74.2 ± 22.7 s vs 52.0 ± 6.1 s (p < .0001); vertical(Vadj) reading time 67.6 ± 17.8 s vs 50.4 ± 6.9 s (p < .0001); Hadj/Vadj ratio 0.9 ± 0.1 vs 1.0 ± 0 (p = .0032), respectively; and eye-tracking test results were fixation number 11.3 ± 3.07 vs 3.51 ± 2.57 (p < .0001); fixation duration 2.01 ± 0.79 s vs 1.5 ± 0.4 s (p = .0013), and time to find target 24.5 ± 8.0 vs 18 ± 9.4 (p = .0034), respectively. CONCLUSIONS: Data showed a lower performance in oculomotor behaviour in people with long COVID-19, compared to healthy individuals. It cannot be affirmed an ocular musculature dysfunction; the differentiated behaviour could be associated to cognitive alterations affected in these people. Both tests used could be an useful tool for the clinical assessment of these participants. Further studies are needed to explore the utility of these procedures.

Global Challenges After a Global Challenge: Lessons Learned from the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) has affected not only individual lives but also the world and global systems, both natural and human-made. Besides millions of deaths and environmental challenges, the rapid spread of the infection and its very high socioeconomic impact have affected healthcare, economic status and wealth, and mental health across the globe. To better appreciate the pandemic's influence, multidisciplinary and interdisciplinary approaches are needed. In this chapter, world-leading scientists from different backgrounds share collectively their views about the pandemic's footprint and discuss challenges that face the international community.

'You're just a Guinea pig': Exploring the barriers and impacts of living with long COVID-19: A view from the undiagnosed.

The COVID-19 pandemic had a disproportionate impact on ethnically minoritised and other marginalised communities, yet little is known about the impacts of long COVID-19 (LC) on this group. Living with LC takes its toll both physically, emotionally and financially and even more so when a diagnosis is hard to come by. By using qualitative interviews centring the view of undiagnosed and marginalised communities already classed as 'underserved' in the medical literature, we show the range of barriers and impacts faced by these groups in the UK, and the strategies of resilience they use. Whether trapped on a 'diagnostic odyssey' at the level of primary care, struggling to maintain employment and businesses, or managing family commitments, we argue many minoritised communities are caught in a liminal space of misrecognition, invalidation and ambiguity. We show how these impacts are generated by tensions and challenges in the process and categorisation of diagnosis, and how this effects the daily lives of many individuals already on the receiving end of health inequity. We also offer some examples and suggestions for best practices.

Long COVID-19 gastrointestinal related disorders and traditional Chinese medicine: A network target-based approach.

The significant number of individuals impacted by the pandemic makes prolonged symptoms after COVID-19 a matter of considerable concern. These are numerous and affect multiple organ systems. According to the World Health Organization (WHO), prolonged gastrointestinal issues are a crucial part of post-COVID-19 syndrome. The resulting disruption of homeostasis underscores the need for a therapeutic approach based on compounds that can simultaneously affect more than one target/node. The present review aimed to check for nutraceuticals possessing multiple molecular mechanisms helpful in relieving Long COVID-19-specific gastrointestinal symptoms. Specific plants used in Keywords Chinese Medicine (TCM) expected to be included in the WHO Global Medical Compendium were selected based on the following criteria: (1) they are widely used in the Western world as natural remedies and complementary medicine adjuvants; (2) their import and trade are regulated by specific laws that ensure quality and safety (3) have the potential to be beneficial in alleviating intestinal issues associated with Long COVID-19. Searches were performed in PubMed, Elsevier, Google Scholar, Scopus, Science Direct, and ResearchGate up to 2023. Cinnamomum cassia, Glycyrrhiza uralensis, Magnolia officinalis, Poria cocos, Salvia miltiorrhiza, Scutellaria baicalensis, and Zingiber officinalis were identified as the most promising for their potential impact on inflammation and oxidative stress. Based on the molecular mechanisms of the phytocomplexes and isolated compounds of the considered plants, their clinical use may lead to benefits in gastrointestinal diseases associated with Long COVID-19, thanks to a multiorgan and multitarget approach.

Postinfectious conditions challenge disease-specificity of SNOT-22.

PURPOSE: The Sino-Nasal-Outcome-Test 22 (SNOT-22) questionnaire assesses treatment outcome and health-related quality of life (HRQOL) in patients with chronic rhinosinusitis (CRS). However, given the overlap between CRS and olfaction in terms of nasal function and the definition of CRS, a fundamental question arises: can patients with olfactory dysfunction (OD) stemming from other causes attain SNOT-22 scores similar to those seen in CRS, even in the absence of CRS? Our study aimed to explore whether OD arising from various postinfectious mechanisms challenges the disease-specificity of SNOT-22 for CRS. If so, could focus on scores within specific symptom domains of SNOT-22 prove valuable in distinguishing between different etiologies. METHODS: The study adopted an observational, retrospective cohort design based on prospectively registered patients and related variables using the REDCap platform. 460 patients experiencing OD due to either (1) simple or (2) complex post-COVID-19, (3) postinfectious non-COVID-19, and (4) CRS, were included in the analysis. RESULTS: The study revealed that the total SNOT-22 score lacks disease-specificity for CRS. This is evident, because complex postinfectious mechanisms resulting from COVID-19 can produce similar symptoms in patients. Notably, elevated total scores were primarily driven by high subdomain scores within the "sleep and cognition" domain. CONCLUSIONS: The application of SNOT-22 as a screening tool needs to be approached with caution, as the total score alone does not provide disease-specific insights. A more thorough exploration of the four symptom domains and the identification of distinctive scoring patterns within the clinical context may prove pivotal in effectively differentiating between various underlying causes.

The effect of long-term COVID-19 on aetiological factors related to nocturia.

AIMS AND OBJECTIVES: This study was conducted to examine the possible aetiology of nocturia in patients with long-term COVID-19. BACKGROUND: Physical and neuropsychiatric symptoms, an increase in overactive bladder symptoms, especially from urinary system complaints, has been reported in patients with COVID-19, 10-14 weeks after the illness. DESIGN: A descriptive design. METHODS: The study consisted of 70 patients who had experienced COVID-19, had nocturia, and were followed in the State Hospital between April and July 2022. Data were collected using a patient information form, the 'TANGO' nocturia screening tool, and the Visual Analog Scale. This study was created in accordance with the STROBE Statement Checklist. RESULTS: When the nocturia effects of long-term COVID-19 were examined it was determined that the urinary tract was the 'priority' aetiological condition. It was observed that there was a significant difference between the aetiological factor groups in terms of the mean age of the patients and the number of nocturia (p < .05). According to post-hoc analysis, the mean age of patients with a dominant cardio-metabolic factor was found to be significantly younger (p < .05). In addition, when comparing the number of nocturia according to the aetiological factors of the patients, it was observed that the number of nocturia was significantly frequent in the patients with a dominant sleep factor (p < .05). CONCLUSIONS: It was found that the urinary tract aetiological factor was dominant in patients with long-term COVID-19 and nocturia, patients with a dominant cardiovascular aetiological factor were younger, and that the number of nocturia was higher in patients with a dominant sleep factor. RELEVANCE TO CLINICAL PRACTICE: Identification of the early signs and symptoms and underlying causes of nocturia in individuals with post-COVID-19 syndrome will enable nurses and health professionals to guide the early identification of different underlying problems, as well as the implementation of approaches to treat and eliminate nocturia. PATIENT OR PUBLIC CONTRIBUTION: The patients contributed to the study by agreeing to participate in the evaluation of nocturia complaints after COVID-19 infection.