COVID-19 is a disease in which early prognosis of severity is critical for desired patient outcomes and for the management of limited resources like intensive care unit beds and ventilation equipment. Many prognostic statistical tools have been developed for the prediction of disease severity, but it is still unclear which ones should be used in practice. We aim to guide clinicians in choosing the best available tools to make optimal decisions and assess their role in resource management and assess what can be learned from the COVID-19 scenario for development of prediction models in similar medical applications. Using the five major medical databases: MEDLINE (via PubMed), Embase, Cochrane Library (CENTRAL), Cochrane COVID-19 Study Register, and Scopus, we conducted a comprehensive systematic review of prediction tools between 2020 January and 2023 April for hospitalized COVID-19 patients. We identified both the relevant confounding factors of tool performance using the MetaForest algorithm and the best tools-comparing linear, machine learning, and deep learning methods-with mixed-effects meta-regression models. The risk of bias was evaluated using the PROBAST tool. Our systematic search identified eligible 27,312 studies, out of which 290 were eligible for data extraction, reporting on 430 independent evaluations of severity prediction tools with ~ 2.8 million patients. Neural Network-based tools have the highest performance with a pooled AUC of 0.893 (0.748-1.000), 0.752 (0.614-0.853) sensitivity, 0.914 (0.849-0.952) specificity, using clinical, laboratory, and imaging data. The relevant confounders of performance are the geographic region of patients, the rate of severe cases, and the use of C-Reactive Protein as input data. 88% of studies have a high risk of bias, mostly because of deficiencies in the data analysis. All investigated tools in use aid decision-making for COVID-19 severity prediction, but Machine Learning tools, specifically Neural Networks clearly outperform other methods, especially in cases when the basic characteristics of severe and non-severe patient groups are similar, and without the need for more data. When highly specific biomarkers are not available-such as in the case of COVID-19-practitioners should abandon general clinical severity scores and turn to disease specific Machine Learning tools.

Following the acute COVID-19 disease, many countries see long-time sequences of this infectious disease, commonly known as Long COVID. This seems to be a multi-organ inflammatory chronic condition of variable intensity and incidence, partly due to the retention of the virus or viral particles in several organs. Based on our 6-country (4 in Europe, 2 from North America) collaborative investigations, we found that the incidence of Long COVID varied from 46 (Mexico) to 17% (Ukraine), the average being 25%. In a summary evaluation of all 6 countries, we characterized as "general" the most frequent presenting signs and symptoms: fatigue (47%), hair loss (39.2%), and myalgia (35%), but no two countries demonstrated the same top 3 clinical signs/symptoms. Hence, we promote the following 3 key points: 1. to expand international collaborations to better understand not only the prevalence and incidence of Long COVID but also to gain insights into the pathogenesis, and identify predisposing factors and diagnostic biomarkers of Long COVID; 2. find or develop new drugs for the treatments of Long COVID and identify appropriate rehabilitation, potentially organ-specific strategies; 3. most importantly, to start long-term observational studies (e.g., for 5-10-15 years) to identify potential increased cancer incidence in any organ, especially, since we know that certain viruses are carcinogens.

The aim of this study is to investigate the early prognostic efficacy of plasma soluble urokinase-type plasminogen activator receptor (suPAR), soluble tumor necrosis factor receptor 1 (sTNFR1), and soluble tumor necrosis factor receptor 2 (sTNFR2) in complicated acute kidney injury (AKI) in patients with coronavirus disease 2019 (COVID-19), and to analyze the relevant factors contributing to complicated AKI in these patients.

Patients with COVID-19 hospitalized at the Affiliated Baiyun Hospital of Guizhou Medical University from March 2022 to March 2024 were selected as study participants. A total of 589 patients met the inclusion and exclusion criteria, 68 patients complicated with AKI were classified as AKI group, and the remaining 521 cases were divided into proportion sampling method and randomly selected 200 samples, which were classified as non-AKI group. Additionally, 50 healthy controls were enrolled as the control group. Logistic regression analysis was conducted to identify the relevant factors associated with complicated AKI in patients with COVID-19. Receiver operating characteristic (ROC) curves were plotted to evaluate the prognostic efficacy of plasma suPAR, sTNFR1, and sTNFR2 indicators for complicated AKI in patients with COVID-19.

Among the patients with COVID-19 in the AKI group, 43 were males (63.20 %), with a median age of 79.00 (interquartile range: 75.00, 83.00) years, while the non-AKI group comprised 83 males (41.50 %), with a median age of 73.00 (interquartile range: 60.00, 80.75) years. Comparison of the sex and age between the two groups indicated that males and elderly patients had increased risks of complicated AKI (P < 0.05). Plasma levels of suPAR, sTNFR1, and sTNFR2 in the AKI group were significantly higher than those in the non-AKI group (P < 0.05). Logistic regression analysis indicated that suPAR and sTNFR2 were independent factors influencing complicated AKI in patients with COVID-19 (P < 0.05). The ROC curve for a single indicator showed that suPAR had the highest prognostic efficacy for complicated AKI, with an area under the curve (AUC) of 0.813, a sensitivity of 79.4 %, and a specificity of 74.0 %. The combined use of suPAR and sTNFR2 for risk assessment yielded the highest AUC of 0.838, with a sensitivity of 66.2 % and a specificity of 87.5 %. The combined risk assessment using all three indicators (suPAR, sTNFR1, and sTNFR2) had an AUC of 0.837, with a sensitivity of 64.7 % and a specificity of 89.0 %.

Elderly patients had increased risks of complicated AKI. Indicators such as suPAR, sTNFR1, and sTNFR2 can assist in assessing the risk in patients with COVID-19 complicated AKI, with suPAR demonstrating the highest prognostic efficacy as a single indicator. The combined detection of suPAR, sTNFR1, and sTNFR2 offers greater prognostic value than using any single indicator.

SARS-CoV-2 infection can result in genitourinary symptoms, such as frequency, urgency, nocturia, and pain/pressure. In this study, we followed the progression of overactive bladder (OAB) symptoms in patients that reported new or worsening OAB symptoms after coronavirus disease-19 (COVID-19) diagnosis.

Individuals from a COVID-19 serology study were invited to participate in a follow-up study. Respondents were divided into three groups based on prior COVID-19 testing. Patients scored symptoms retrospectively before the pandemic, at study onset, and prospectively during 12-month follow-up. Genitourinary symptoms were assessed using international consultation on incontinence questionaire for OAB (ICIQ-OAB). Change in ICIQ-OAB scores from baseline were calculated. The minimal important difference of one on ICIQ-OAB is considered a significant change.

26.0% of participants previously had positive COVID polymerase chain reaction (PCR) test (PCR+), 5.6% a positive serology test only (Ser+), and 65.5% were COVID naïve (COVID-). 23.8% of participants reported a significant increase in ICIQ-OAB score at study onset compared to prepandemic. ICIQ-OAB scores were similar at prepandemic but significantly higher at study start (p < 0.001) in PCR+ group. During follow-up, change in ICIQ-OAB scores from baseline remained unchanged for COVID- group, but gradually reduced for PCR+, reaching similar levels as COVID- group by 12 months. By 12 months, 71.4% of PCR+, 42.9% of Ser+, and 68.8% of COVID- participants still reported significant increase in ICIQ-OAB scores.

Most COVID-19 patients experienced return of symptoms to baseline, indicative of the potential resolution of COVID-associated cystitis. A subset of cases did not, raising questions about the underlying factors contributing to this outcome. Additional research is needed to assess long COVID on urological health.

This study aimed to investigate the clinical characteristics and prognostic factors of critically ill COVID-19 patients with renal failure admitted to the ICU.

We analyzed 300 adult patients with SARS-CoV-2 infection admitted to the ICU between November 1, 2020, and June 1, 2022. Demographic data, renal function parameters, and outcomes were collected and analyzed.

The median age was 72 years, and 54.3% were men. Mechanical ventilation was required for 86.3% of patients, with 71.0% needing invasive ventilation. Renal failure was present in 43.3% of patients at ICU admission, significantly associated with older age, higher mechanical and invasive ventilation needs, and increased ICU mortality (76.9% vs. 51.8%, p<0.001). Patients with renal failure had elevated levels of urea, creatinine, C-reactive protein (CRP), D-dimer, white blood cell (WBC), neutrophil (Neu), and procalcitonin (PCT) (p<0.001 for all). Among patients with acute kidney injury (AKI), those with AKI had significantly higher median age (75 vs. 66 years, p<0.001), mechanical ventilation requirement (93.6% vs. 74.3%, p<0.001) and ICU mortality (79.1% vs. 35.4%, p<0.001). Elevated levels of urea (76 vs. 44 mg/dL, p<0.001) and creatinine (1.4 vs. 0.8 mg/dL, p<0.001), as well as inflammatory markers CRP and D-dimer (p=0.001), were observed in AKI patients. Survivors had lower median age (66.0 vs. 74.0 years, p<0.001) and lower prevalence of chronic kidney disease (CKD) (4.5% vs. 12.8, p=0.019) and AKI (34.8% vs. 78.7%, p<0.001). Non-survivors exhibited higher levels of urea, creatinine, lactate dehydrogenase (LDH), CRP, ferritin, and D-dimer (p<0.001 for all).

Renal failure and AKI are prevalent in critically ill COVID-19 patients and are associated with worse outcomes. Elevated creatinine and urea levels at ICU admission are significant predictors of ICU mortality, underscoring the importance of early recognition and management of renal impairment in these patients.

With the rapid global spread of COVID-19, it has become evident that the virus can lead to multisystem complications, leading to a significant increase in related publications. Bibliometrics serves as a valuable tool for identifying highly cited literature and research hotspots within specific areas.

The aim of this study is to identify current research hotspots and future trends in COVID-19 complications.

The dataset was obtained from the Web of Science Core Collection, covering COVID-19 complications from December 8, 2019, to October 31, 2022. Various aspects, including publication general information, authors, journals, co-cited authors, co-cited references, research hotspots, and future trends, were subjected to analysis. Visual analysis was conducted using VOSviewer, The Online Analysis Platform of Literature Metrology, and Charticulator.

There were 4597 articles in the study. The top three countries with the most published articles are the USA (n = 1350, 29.4 %), China (n = 765, 16.6 %), and Italy (n = 623, 13.6 %). USA and China have the closest collaborative relationship. The institute with the largest number of publications is Huazhong University of Science and Technology, followed by Harvard Medical School. Nevertheless, half of the top 10 institutes belong to the USA. "Rezaei, Nima" published 13 articles and ranked first, followed by "Yaghi, Shadi" with 12 articles and "Frontera, Jennifer" with 12 articles. The journal with the largest number of publications is "Journal of Clinical Medicine". The top 3 co-cited authors are "Zhou, Fei", "Guan, Wei-Jie", "Huang, Chaolin". The top 3 co-cited references addressed COVID-19's clinical features in China and noticed that COVID-19 patients had a wide range of complications. We also list four research hotspots.

This study conducted a bibliometric visual analysis of the literature on COVID-19 complications and summarized the current research hotspots. This study may provide valuable insights into the complications of COVID-19.

This study presents the interaction with the human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a protein-protein interaction network analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2753 proven interactions and 1708 interactors specific to ORF7b. We used these proteins as functional seeds, and we obtained a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. By following a hub-and-spoke network architectural model, we were able to identify seven proteins that ranked high as hubs and an additional seven as bottlenecks. Through this interaction model, we identified significant GO-processes (5057 terms in 15 categories) induced in human metabolism by ORF7b. We discovered high statistical significance processes of dysregulated molecular cell mechanisms caused by acting ORF7b. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems, and the molecular mechanisms that supervise programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant Connected Component core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation and transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes within the limits of the poor knowledge that these sectors still impose.

Background Low back pain (LBP) is a common musculoskeletal condition that affects individuals worldwide, causing difficulties in daily tasks and social interactions. It can be categorized based on chronicity, with acute, subacute, and chronic forms. The causes of backache vary among patients and can include inflammatory conditions, radiculopathy, pregnancy, trauma, osteoporosis, nerve root compression, cancer, plexopathy, infection, and other spinal diseases. Aim The aim is to investigate the association between COVID-19 infection and LBP between all Saudi adults and foreign adults who had positive COVID-19 tests in the eastern region of Saudi Arabia. Methods A cross-sectional study was conducted in the Eastern Province of Saudi Arabia over the period from March 2023 to August 2023. Participants were selected by using a convenience sampling method, a sample (n=500) of individuals. The structured questionnaire was used to gather information on sociodemographic variables and COVID-related features. All the statistical calculations were performed using the SPSS software (by IBM) version 29.0.0. Results 482 participants completed the questionnaire. Out of 482 participants, the majority were females with a number of 372 (77.2%) aged between 20 and 29 years (38.4%). Out of the remaining participants, 110 (22.8%) were males. Most of the participants with a number of 301 (62.4%) were from the Hasa province. This was followed by Qatif (79, 16.4%), Dammam (56, 11.6%), Jubail (25, 5.2%), and others (21, 4.4%). The study revealed that 10.1% of participants reported experiencing back pain. The duration of backaches varied among respondents, with 122 (25.3%) experiencing them from a day to a week, 28 (5.8%) enduring them for six weeks, and 65 (13.5%) reporting a duration of six to 12 weeks. The majority, comprising 267 (55.4%) respondents, were uncertain about the period of their backaches. The prevalence of COVID-19 infection among the participants was 357 (74.1%), and 477 (99.0%) had been vaccinated against COVID-19. Approximately 44.4% of the participants experienced back pain, and out of those, 28.2% reported having pain during quarantine. Among the individuals with back pain, 24.7% attributed it to COVID-19. Conclusion This study highlights the significant correlation between back pain and COVID-19, even after the resolution of other symptoms. It underscores the importance of further research into the long-term effects and mechanisms of this association. The findings emphasize the need for healthcare professionals to consider back pain as a potential aspect of the post-COVID-19 symptom profile, ensuring comprehensive care for affected individuals.

The effects of SARS-CoV-2 in COVID-19 on the nervous system are incompletely understood. SARS-CoV-2 can infect endothelial cells, neurons, astrocytes, and oligodendrocytes with consequences for the host. There are indications that infection of these CNS-resident cells may result in long-term effects, including emergence of neurodegenerative diseases. Indirect effects of infection with SARS-CoV-2 relate to the induction of autoimmune disease involving molecular mimicry or/and bystander activation of T- and B cells and emergence of autoantibodies against various self-antigens. Data obtained in preclinical models of coronavirus-induced disease gives important clues for the understanding of nervous system-related assault of SARS-CoV-2. The pathophysiology of long-COVID syndrome and post-COVID syndrome in which autoimmunity and immune dysregulation might be the driving forces are still incompletely understood. A better understanding of nervous-system-related immunity in COVID-19 might support the development of therapeutic approaches. In this review, the current understanding of SARS-CoV-2 tropism for the nervous system, the associated immune responses, and diseases are summarized. The data indicates that there is viral tropism of SARS-CoV-2 in the nervous system resulting in various disease conditions. Prevention of SARS-CoV-2 infection by means of vaccination is currently the best strategy for the prevention of subsequent tissue damage involving the nervous system.

Coronaviruses (CoVs) belong to the RNA viruses family. The viruses in this family are known to cause mild respiratory disease in humans. The origin of the novel SARS-COV2 virus that caused the coronavirus-19 disease (COVID-19) is the Wuhan city in China from where it disseminated to cause a global pandemic. Although lungs are the predominant target organ for Coronavirus Disease-19 (COVID-19), since its outbreak, the disease is known to affect heart, blood vessels, kidney, intestine, liver and brain. This review aimed to summarize the catastrophic impacts of Coronavirus disease-19 on heart and liver along with its mechanisms of pathogenesis.

The information used in this review was obtained from relevant articles published on PubMed, Google Scholar, Google, WHO website, CDC and other sources. Key searching statements and phrases related to COVID-19 were used to retrieve information. Original research articles, review papers, research letters and case reports were used as a source of information.

Besides causing severe lung injury, COVID-19 has also been reported to affect and cause dysfunction of many other organs. COVID-19 infection can affect people by downregulating membrane-bound active angiotensin-converting enzyme (ACE). People who have deficient ACE2 expression are more vulnerable to COVID-19 infection. The patients' pre-existing co-morbidities are major risk factors that predispose individuals to severe COVID-19.

The disease severity and its broad spectrum phenotype is a result of combined direct and indirect pathogenic factors. Therefore, protocols that harmonize many therapeutic preferences should be the best alternatives to de-escalate the disease and obviate deaths caused as a result of multiple organ damage and dysfunction induced by the disease.

As the coronavirus disease 2019 (COVID-19) pandemic progressed, the virus was found to cause long-term health complications known as long COVID (LC). This study aimed to investigate LC symptom severity and the factors associated with the likelihood of persistence beyond 1 year among COVID-19 survivors in Saudi Arabia.

This descriptive, cross-sectional, questionnaire-based study was conducted via convenience sampling between December 1, 2023, and March 1, 2024. In-person interviews were performed, and 845 individuals with persistent symptoms after acute COVID-19 were included.

Hair loss and memory impairment were the most reported symptoms. In predicting LC persistence beyond 12 months, women were found to have higher odds of being symptomatic than men, and individuals from moderate-to-high-income households were more likely to report persistent symptoms than those from low-income households. Each additional acute COVID-19 symptom increased the likelihood of persistent symptoms by 1.14 times. Reporting more symptoms in the first 6 months post-infection significantly reduced the odds of long-term symptoms by approximately 30%.

LC symptom severity varies among patients, and sociodemographic and clinical factors influence the likelihood of experiencing symptoms beyond 1 year. Understanding these factors can provide insights and help optimize management, leading to improved patient outcomes.

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate the potential of small molecules from natural products to offer neuroprotection in models of neurodegenerative diseases. Through our analysis, we discovered that flavonoids, alkaloids, terpenoids, and other natural compounds exhibit neuroprotective effects by modulating signaling pathways known to be impacted by COVID-19. Some of these compounds also directly target SARS-CoV-2 viral replication. Therefore, molecules of natural origin show promise as potential agents to prevent or mitigate nervous system damage in COVID-19 patients. Further research and the evaluation of different stages of the disease are warranted to explore their potential benefits.

Amyloidosis is one of the rare systemic illnesses characterized by the deposition of amyloid fibrils in various organs and tissues. There is a common point between COVID-19 and systemic amyloidosis regarding the multiorgan involvement in the pathological process which leads to a heightened risk for severe morbidity and mortality in amyloidosis patients who contracted COVID-19. We performed a pathomorphological analysis of the autopsy records of 22 patients who had COVID-19 and pre-existing systemic amyloidosis. The premortem diagnosis of systemic amyloidosis was established in 55% of patients, and in other 45% of cases, amyloidosis was found at autopsy. Based on the results of immunohistochemical amyloid typing, amyloid A (AA) amyloidosis was detected in 23%, amyloid light chain (AL) lambda in 32%, AL kappa-in 9%, and transthyretin (ATTR) amyloidosis-in 36% of observations. Immunohistochemical staining with an antibody against SARS-CoV-2 Spike (S) protein revealed positive immune reactions in type II alveolocytes in 59% of deceased persons. The analysis of autopsy findings indicates that patients with systemic amyloidosis are more likely to experience an aggressive clinical course of COVID-19 which leads to a multiorgan failure and a higher risk of fatal outcome.

Approximately one third of non-hospitalized coronavirus disease of 2019 (COVID-19) patients report chronic symptoms after recovering from the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some of the most persistent and common complaints of this post-acute COVID-19 syndrome (PACS) are cognitive in nature, described subjectively as "brain fog" and also objectively measured as deficits in executive function, working memory, attention, and processing speed. The mechanisms of these chronic cognitive sequelae are currently not understood. SARS-CoV-2 inflicts damage to cerebral blood vessels and the intestinal wall by binding to angiotensin-converting enzyme 2 (ACE2) receptors and also by evoking production of high levels of systemic cytokines, compromising the brain's neurovascular unit, degrading the intestinal barrier, and potentially increasing the permeability of both to harmful substances. Such substances are hypothesized to be produced in the gut by pathogenic microbiota that, given the profound effects COVID-19 has on the gastrointestinal system, may fourish as a result of intestinal post-COVID-19 dysbiosis. COVID-19 may therefore create a scenario in which neurotoxic and neuroinflammatory substances readily proliferate from the gut lumen and encounter a weakened neurovascular unit, gaining access to the brain and subsequently producing cognitive deficits. Here, we review this proposed PACS pathogenesis along the gut-brain axis, while also identifying specific methodologies that are currently available to experimentally measure each individual component of the model.

Vitamin D deficiency is a substantial public health problem. The present study evaluated the association between vitamin D concentration and hospitalization and mortality risk in patients with coronavirus disease 19 (COVID-19).

This study used the COronavirus in LOwer Silesia (COLOS) dataset collected between February 2020 and June 2021. The medical records of 474 patients with confirmed severe acute respiratory syndrome 2 (SARS-CoV-2) infection, and whose vitamin D concentration was measured, were analyzed.

We determined a significant difference in vitamin D concentration between discharged patients and those who died during hospitalization (p = 0.0096). We also found an effect of vitamin D concentration on the risk of death in patients hospitalized due to COVID-19. As vitamin D concentration increased, the odds ratio (OR) for death slightly decreased (OR = 0.978; 95% confidence interval [CI] = 0.540-0.669). The vitamin D concentration cutoff point was 15.40 ng/ml. In addition, patients with COVID-19 and serum 25-hydroxyvitamin D (25(OH)D) concentrations < 30 ng/ml had a lower survival rate than those with serum 25(OH)D ≥ 30 ng/ml (log-rank test p = 0.0018). Moreover, a Cox regression model showed that patients with an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 and higher vitamin D concentrations had a 2.8% reduced risk of mortality (hazard ratio HR = 0.972; CI = 0.95-0,99; p = 0.0097).

The results indicate an association between 25(OH)D levels in patients with COVID-19 and the final course of hospitalization and risk of death.

SARS-CoV-2 causes substantial extrapulmonary manifestations in addition to pulmonary disease. Some of the major organs affected are cardiovascular, hematological and thrombotic, renal, neurological, and digestive systems. These types of muti-organ dysfunctions make it difficult and challenging for clinicians to manage and treat COVID-19 patients. The article focuses to identify potential protein biomarkers that can flag various organ systems affected in COVID-19. Publicly reposited high throughput proteomic data from human serum (HS), HEK293T/17 (HEK) and Vero E6 (VE) kidney cell culture were downloaded from ProteomeXchange consortium. The raw data was analyzed in Proteome Discoverer 2.4 to delineate the complete list of proteins in the three studies. These proteins were analyzed in Ingenuity Pathway Analysis (IPA) to associate them to various organ diseases. The shortlisted proteins were analyzed in MetaboAnalyst 5.0 to shortlist potential biomarker proteins. These were then assessed for disease-gene association in DisGeNET and validated by Protein-protein interactome (PPI) and functional enrichment studies (GO_BP, KEGG and Reactome pathways) in STRING. Protein profiling resulted in shortlisting 20 proteins in 7 organ systems. Of these 15 proteins showed at least 1.25-fold changes with a sensitivity and specificity of 70%. Association analysis further shortlisted 10 proteins with a potential association with 4 organ diseases. Validation studies established possible interacting networks and pathways affected, confirmingh the ability of 6 of these proteins to flag 4 different organ systems affected in COVID-19 disease. This study helps to establish a platform to seek protein signatures in different clinical phenotypes of COVID-19. The potential biomarker candidates that can flag organ systems involved are: (a) Vitamin K-dependent protein S and Antithrombin-III for hematological disorders; (b) Voltage-dependent anion-selective channel protein 1 for neurological disorders; (c) Filamin-A for cardiovascular disorder and, (d) Peptidyl-prolyl cis-trans isomerase A and Peptidyl-prolyl cis-trans isomerase FKBP1A for digestive disorders.

The development of liver dysfunction in patients having various systemic diseases is common and has a broad differential diagnosis, at times being the initial manifestation of the disorder. Liver injury associated with systemic lupus erythematosus is heterogeneous and may present with nonspecific histology. Differentiating autoimmune hepatitis from lupus hepatitis is challenging on histologic grounds alone. Other systemic diseases that may present mostly with nonspecific findings are rheumatoid arthritis and celiac disease. More recently COVID-19 cholangiopathy and secondary sclerosing cholangitis have become increasingly recognized as distinct liver conditions. Many patients may also have intrinsic liver disease or may develop drug-induced liver injury from the treatment of the systemic disease. Timely identification of the cause of the liver dysfunction is essential and liver biopsy may help the clinician in diagnosis and management.

Cognitive difficulties are a frequent complaint in long COVID and persist for more than a year post- infection. There is a lack of evidence-based data on effective intervention strategies. Non-pharmacological intervention programs that are used with other neurological populations have not yet been the subject of controlled trials. COVCOG is a multicentric, randomized trial comparing cognitive intervention and a cognitive-behavioural counselling.

Patients with long covid are selected and recruited at least three months post-infection. Patients are randomised in a 1:1 ratio into the cognitive (neuropsychological psychoeducation) and affective (emotion management with cognitive-behavioural counselling) intervention arms. The inclusion of 130 patients is planned. The cognitive intervention includes psycho-educational modules on fatigue and sleep, attention and working memory, executive functions and long-term memory. The affective intervention includes modules on emotion recognition and communication, uncertainty management and behavioral activation. The main objective is to reduce cognitive complaints 2 months after the intervention. A Follow-up is also planned at 8 months.

Given the long-term effects of Covid on cognition and the negative effects of cognitive impairment on quality of life and social participation, it is important to determine whether low-dose, non-pharmacological interventions can be effective. The trial will determine which of the usual types of intervention is the most effective.

Clinicaltrials.gov Number: NCT05167266 (21/12/ 2021).

Although the exact prevalence of post-COVID-19 condition (also known as long COVID) is unknown, more than a third of patients with COVID-19 develop symptoms that persist for more than 3 months after SARS-CoV-2 infection. These sequelae are highly heterogeneous in nature and adversely affect multiple biological systems, although breathlessness is a frequently cited symptom. Specific pulmonary sequelae, including pulmonary fibrosis and thromboembolic disease, need careful assessment and might require particular investigations and treatments. COVID-19 outcomes in people with pre-existing respiratory conditions vary according to the nature and severity of the respiratory disease and how well it is controlled. Extrapulmonary complications such as reduced exercise tolerance and frailty might contribute to breathlessness in post-COVID-19 condition. Non-pharmacological therapeutic options, including adapted pulmonary rehabilitation programmes and physiotherapy techniques for breathing management, might help to attenuate breathlessness in people with post-COVID-19 condition. Further research is needed to understand the origins and course of respiratory symptoms and to develop effective therapeutic and rehabilitative strategies.

Understanding the genetic risk and mechanisms through which SARS-CoV-2 infection outcomes and comorbidities interact to impact acute and long-term sequelae is essential if we are to reduce the ongoing health burdens of the COVID-19 pandemic. Here we use a de novo protein diffusion network analysis coupled with tissue-specific gene regulatory networks, to examine putative mechanisms for associations between SARS-CoV-2 infection outcomes and comorbidities. Our approach identifies a shared genetic aetiology and molecular mechanisms for known and previously unknown comorbidities of SARS-CoV-2 infection outcomes. Additionally, genomic variants, genes and biological pathways that provide putative causal mechanisms connecting inherited risk factors for SARS-CoV-2 infection and coronary artery disease and Parkinson's disease are identified for the first time. Our findings provide an in depth understanding of genetic impacts on traits that collectively alter an individual's predisposition to acute and post-acute SARS-CoV-2 infection outcomes. The existence of complex inter-relationships between the comorbidities we identify raises the possibility of a much greater post-acute burden arising from SARS-CoV-2 infection if this genetic predisposition is realised.

Assessing long/post-COVID syndrome (PCS) following an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a multidisciplinary challenge due to the diverse and complex symptoms. Besides discipline-specific evaluation of infection-related organ damage, the main issue is expert objectivity and causality assessment regarding subjective symptoms. The consequences of long/PCS raise questions of insurance rights in all fields of law. In cases of persistent impairment of performance, determining reduction in earning capacity is crucial for those affected. Recognition as an occupational disease (BK no. 3101) is vital for employees in healthcare and welfare sectors, along with occupational accident recognition and assessing the illness's consequences, including the reduction in earning capacity (MdE) in other sectors or work areas. Therefore, expert assessments of illness consequences and differentiation from previous illnesses or damage disposition are necessary in all areas of law, individually based on corresponding organ manifestations in medical fields and interdisciplinarily for complex late sequelae, for instance, by internists with appropriate qualifications for pulmonary or cardiac manifestations and neurologists, psychiatrists, and neuropsychologists for neurological and psychiatric manifestations, etc.

Although the novel severe acute respiratory syndrome coronavirus-2 is known primarily to affect the respiratory system, current evidence supports its capability to infect and induce gastrointestinal tract injury. Data describing the histopathologic alterations of the digestive system in patients infected with severe acute respiratory syndrome coronavirus-2 are becoming more detailed, as the number of studies is increasing and the quality of our insight into the infection and the histopathologic findings is improving. This review highlights the range of pathologic findings that could be observed in gastrointestinal specimens from patients infected with coronavirus disease 2019 and the potential underlying pathogenetic mechanisms of this disease.

(1) Background: SARS-CoV-2 infection during pregnancy could determine important maternal and fetal complications. We aimed to prospectively assess placental immunohistochemical changes, immunophenotyping alterations, and pregnancy outcomes in a cohort of patients with COVID-19; (2) Methods: 52 pregnant patients admitted to a tertiary maternity center between October 2020 and November 2021 were segregated into two equal groups, depending on the presence of SARS-CoV-2 infection. Blood samples, fragments of umbilical cord, amniotic membranes, and placental along with clinical data were collected. Descriptive statistics and a conditional logistic regression model were used for data analysis; (3) Results: Adverse pregnancy outcomes such as preterm labor and neonatal intensive care unit admission did not significantly differ between groups. The immunophenotyping analysis indicated that patients with moderate-severe forms of COVID-19 had a significantly reduced population of T lymphocytes, CD4+ T cells, CD8+ T cells (only numeric), CD4+/CD8+ index, B lymphocytes, and natural killer (NK) cells. Our immunohistochemistry analysis of tissue samples failed to demonstrate positivity for CD19, CD3, CD4, CD8, and CD56 markers; (4) Conclusions: Immunophenotyping analysis could be useful for risk stratification of pregnant patients, while further studies are needed to determine the extent of immunological decidual response in patients with various forms of COVID-19.

Cardiac consequences occur in both acute COVID-19 and post-acute sequelae of COVID-19 (PASC). Here, we highlight the current understanding about COVID-19 cardiac effects, based upon clinical, imaging, autopsy, and molecular studies.

COVID-19 cardiac effects are heterogeneous. Multiple, concurrent cardiac histopathologic findings have been detected on autopsies of COVID-19 non-survivors. Microthrombi and cardiomyocyte necrosis are commonly detected. Macrophages often infiltrate the heart at high density but without fulfilling histologic criteria for myocarditis. The high prevalences of microthrombi and inflammatory infiltrates in fatal COVID-19 raise the concern that recovered COVID-19 patients may have similar but subclinical cardiac pathology. Molecular studies suggest that SARS-CoV-2 infection of cardiac pericytes, dysregulated immunothrombosis, and pro-inflammatory and anti-fibrinolytic responses underlie COVID-19 cardiac pathology. The extent and nature by which mild COVID-19 affects the heart is unknown. Imaging and epidemiologic studies of recovered COVID-19 patients suggest that even mild illness confers increased risks of cardiac inflammation, cardiovascular disorders, and cardiovascular death. The mechanistic details of COVID-19 cardiac pathophysiology remain under active investigation. The ongoing evolution of SARS-CoV-2 variants and vast numbers of recovered COVID-19 patients portend a burgeoning global cardiovascular disease burden. Our ability to prevent and treat cardiovascular disease in the future will likely depend on comprehensive understanding of COVID-19 cardiac pathophysiologic phenotypes.

During the first wave of the pandemic, coronavirus disease 2019 (COVID-19) infection has been considered mainly as a pulmonary infection. However, different clinical and radiological manifestations were observed over time, including involvement of abdominal organs. Nowadays, the liver is considered one of the main affected abdominal organs. Hepatic involvement may be caused by either a direct damage by the virus or an indirect damage related to COVID-19 induced thrombosis or to the use of different drugs. After clinical assessment, radiology plays a key role in the evaluation of liver involvement. Ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) may be used to evaluate liver involvement. US is widely available and it is considered the first-line technique to assess liver involvement in COVID-19 infection, in particular liver steatosis and portal-vein thrombosis. CT and MRI are used as second- and third-line techniques, respectively, considering their higher sensitivity and specificity compared to US for assessment of both parenchyma and vascularization. This review aims to the spectrum of COVID-19 liver involvement and the most common imaging features of COVID-19 liver damage.

In the current COVID-19 pandemic, clinicians require a manageable set of decisive parameters that can be used to (i) rapidly identify SARS-CoV-2 positive patients, (ii) identify patients with a high risk of a fatal outcome on hospital admission, and (iii) recognize longitudinal warning signs of a possible fatal outcome.

This comparative study was performed in 515 patients in the Maria Skłodowska-Curie Specialty Voivodeship Hospital in Zgierz, Poland. The study groups comprised 314 patients with COVID-like symptoms who tested negative and 201 patients who tested positive for SARS-CoV-2 infection; of the latter, 72 patients with COVID-19 died and 129 were released from hospital. Data on which we trained several machine learning (ML) models included clinical findings on admission and during hospitalization, symptoms, epidemiological risk, and reported comorbidities and medications.

We identified a set of eight on-admission parameters: white blood cells, antibody-synthesizing lymphocytes, ratios of basophils/lymphocytes, platelets/neutrophils, and monocytes/lymphocytes, procalcitonin, creatinine, and C-reactive protein. The medical decision tree built using these parameters differentiated between SARS-CoV-2 positive and negative patients with up to 90-100% accuracy. Patients with COVID-19 who on hospital admission were older, had higher procalcitonin, C-reactive protein, and troponin I levels together with lower hemoglobin and platelets/neutrophils ratio were found to be at highest risk of death from COVID-19. Furthermore, we identified longitudinal patterns in C-reactive protein, white blood cells, and D dimer that predicted the disease outcome.

Our study provides sets of easily obtainable parameters that allow one to assess the status of a patient with SARS-CoV-2 infection, and the risk of a fatal disease outcome on hospital admission and during the course of the disease.

COVID-19 causes morbid pathological changes in different organs including lungs, kidneys, liver, and so on, especially in those who succumb. Though clinical outcomes in those with comorbidities are known to be different from those without-not much is known about the differences at the histopathological level. To compare the morbid histopathological changes in COVID-19 patients between those who were immunocompromised (Gr 1), had a malignancy (Gr 2), or had cardiometabolic conditions (hypertension, diabetes, or coronary artery disease) (Gr 3), postmortem tissue sampling (minimally invasive tissue sampling [MITS]) was done from the lungs, kidney, heart, and liver using a biopsy gun within 2 hours of death. Routine (hematoxylin and eosin) and special staining (acid fast bacilli, silver methanamine, periodic acid schiff) was done besides immunohistochemistry. A total of 100 patients underwent MITS and data of 92 patients were included (immunocompromised: 27, malignancy: 18, cardiometabolic conditions: 71). In lung histopathology, capillary congestion was more in those with malignancy, while others like diffuse alveolar damage, microthrombi, pneumocyte hyperplasia, and so on, were equally distributed. In liver histopathology, architectural distortion was significantly different in immunocompromised; while steatosis, portal inflammation, Kupffer cell hypertrophy, and confluent necrosis were equally distributed. There was a trend towards higher acute tubular injury in those with cardiometabolic conditions as compared to the other groups. No significant histopathological difference in the heart was discerned. Certain histopathological features were markedly different in different groups (Gr 1, 2, and 3) of COVID-19 patients with fatal outcomes.

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hepatic involvement is common in SARS-CoV-2-infected individuals. It is currently accepted that the direct and indirect hepatic effects of SARS-CoV-2 infection play a significant role in COVID-19. In individuals with pre-existing infectious and non-infectious liver disease, who are at a remarkably higher risk of developing severe COVID-19 and death, this pathology is most medically relevant. This review emphasizes the current pathways regarded as contributing to the gastrointestinal and hepatic ailments linked to COVID-19-infected patients due to an imbalanced interaction among the liver, systemic inflammation, disrupted coagulation, and the lung.

Organ-on-a-chip (OOC) systems are engineered nanobiosystems to mimic the physiochemical environment of a specific organ in the body. Among various components of OOC systems, biomimetic membranes have been regarded as one of the most important key components to develop controllable biomimetic bioanalysis systems. Here, we review the preparation and characterization of biomimetic membranes in comparison with the features of the extracellular matrix. After that, we review and discuss the latest applications of engineered biomimetic membranes to fabricate various organs on a chip, such as liver, kidney, intestine, lung, skin, heart, vasculature and blood vessels, brain, and multiorgans with perspectives for further biomedical applications.

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

The benefits of physical exercise are well-known, but there are still many questions regarding COVID-19. Chow et al.'s 2022 study, titled Exerkines and Disease, showed that a special focus on exerkines can help to better understand the underlying mechanisms of physical exercise and disease. Exerkines are a group of promising molecules that may underlie the beneficial effects of physical exercise in diseases. The idea of exerkines is to understand the effects of physical exercise on diseases better. Exerkines have a high potential for the treatment of diseases and, considering that, there is still no study of the importance of exerkines on the most dangerous disease in the world in recent years, COVID-19. This raises the fundamental question of whether exerkines have the potential to manage COVID-19. Most of the studies focused on the general changes in physical exercise in patients with COVID-19, both during the illness and after discharge from the hospital, and did not investigate the basic differences. A unique look at the management of COVID-19 by exerkines, especially in obese and overweight women who experience high severity of COVID-19 and whose recovery period is long after discharge from the hospital, can help to understand the basic mechanisms. In this review, we explore the potential of exerkines in COVID-19 by practicing physical exercise to provide compelling practice recommendations with new insights.

We herein report a case of cerebral infarct in a patient with coronavirus disease 2019 (COVID-19) infection who died of aspiration pneumonia. The postmortem examination of the brain revealed embolic infarct with negative findings on quantitative reverse transcription polymerase chain reaction (qRT-PCR) as well as immunohistochemistry to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The systemic examination only revealed low copy numbers of SARS-CoV-2 in the bronchus. This is the first and so far only autopsy case of COVID-19 infection with pathologic and virologic findings of the postmortem brain in Japan.

Paxlovid has shown the potential decreasing the hospitalization rate of mild or moderate coronavirus disease 2019 (COVID-19) and death in few of clinical trials, and is expected to the most promising medicine targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SRAS-COV-2). However, there are no enough evidences to show it effectiveness for all patients with SARS-COV-2, especially among elderly patients and newest Omicron variant.

A 79 year's old female patient was admitted to hospital because of the moderate COVID-19 caused by the Omicron variant BA2.0. He presented the initial syndromes including Xerostomia, cough and fever. Chest computed tomography (CT) scanning at admission showed the exudation lesions on lung. The laboratory examination revealed that there are increased C-reactive protein (CRP), Ferritin and erythrocytesedimentationrate (ESR) and decreased white blood cells.

The oral Paxlovid (Nirmatrelvir/Ritonavir) was administrated on second day after admission.

The syndromes of Xerostomia, cough and fever was improved on third day after use of Paxlovid. The levels of CRP, ESR and counts of white blood cells returned the normal after three days of admission. The chest CT scanned on the third and sixth day after Paxlovid used showed the absorption of lesions. The examination of SARS-COVS viral nucleic acid turned negative at fifth day of admission.

As a result, we would consider that Paxlovid is a suitable oral drug for elderly patients with SARS-COV2 even Omicron variant, it's benefit to improve patient's symptom and signs and can prevents COVID-19 with the high-risk factors from severe disease, although it didn't shorten the time for viral nucleic acid to turn negative.

Knowledge on SARS-CoV-2 infection and its resultant COVID-19 in liver diseases has rapidly increased during the pandemic. Hereby, we review COVID-19 liver manifestations and pathophysiological aspects related to SARS-CoV-2 infection in patients without liver disease as well as the impact of COVID-19 in patients with chronic liver disease (CLD), particularly cirrhosis and liver transplantation (LT). SARS-CoV-2 infection has been associated with overt proinflammatory cytokine profile, which probably contributes substantially to the observed early and late liver abnormalities. CLD, particularly decompensated cirrhosis, should be regarded as a risk factor for severe COVID-19 and death. LT was impacted during the pandemic, mainly due to concerns regarding donation and infection in recipients. However, LT did not represent a risk factor per se of worse outcome. Even though scarce, data regarding COVID-19 specific therapy in special populations such as LT recipients seem promising. COVID-19 vaccine-induced immunity seems impaired in CLD and LT recipients, advocating for a revised schedule of vaccine administration in this population.

SARS-COV-2 is associated with unexpected symptoms. Several studies in adults reported urinary frequency with COVID-19. The aim of this study is to reveal lower urinary tract symptoms associated with COVID-19 (CALUTS) in children.

All children diagnosed with COVID-19 and associated multisystem inflammatory syndrome in children (MIS-C) between November 2020-June 2021 in our hospital were reviewed and asked for urinary symptoms at the time of or following their disease. The ones reporting symptoms were invited for further evaluation. Parents were inquired for their child's former bladder and bowel function, their symptoms after the diagnosis of COVID-19 or MIS-C, onset and duration of the symptoms, and their current state. They were questioned for the frequency of voiding as well as dysuria, odor, and the presence of incontinence as well as other symptoms of COVID-19. The patients who reported symptoms at the time of inquiry were followed for cessation of symptoms. The parameters age, sex, need for hospitalization and admission to ICU were also compared to the whole group to evaluate the main characteristics of patients with lower urinary tract symptoms.

In total 20 patients (18/216 with acute disease and 2/36 with MIS-C) reported CALUTS (figure). Age and sex distribution were not significantly different from the patients without urinary symptoms (p = 0.777 and p = 0.141 respectively). All were otherwise healthy children with no concomitant chronic diseases other than overactive bladder in two. There were 13 girls and 7 boys. Mean age was 11 years (±5 years). Thirteen of the patients were older than 10 years; however, there were also 3 children under 5 years of age. All parents described a sudden onset of extremely increased urinary frequency and urgency lasting for weeks which disappeared gradually. Median bladder and bowel dysfunction questionnaire (BBDQ) score before COVID-19 was 2.5 (1-18) which increased to a median of 22 (15-29) at the time of the symptoms (p < 0.001). The timing of onset and duration of symptoms were variable and not associated with symptom severity (p = 0.306 and p = 0.450 respectively). Eight patients (40%) reported diarrhea. The duration of diarrhea was limited to less than one week in all.

Our study revealed that SARS-COV-2 can be associated with lower urinary tract symptoms also in children both during the acute phase and MIS-C. Further studies are necessary to understand the etiopathogenesis and prevalence of this unexpected aspect of COVID-19.

Thrombolysis in Myocardial Infarction Frame Count (TFC) is an index that provides a quantitative evaluation of coronary microvascular dysfunction. In this study, we aimed to examine the effect of COVID-19 infection on TFC in patients admitted with chest pain and dyspnoea after COVID-19 disease and had abnormal findings in myocardial perfusion scintigraphy.

For this single-center retrospective study, patients with and without a history of COVID-19 who were underwent coronary angiography for abnormal findings in myocardial perfusion scintigraphy between January 1, 2021 and June 30, 2021 were analysed. Patients were divided into two groups as patients with COVİD-19 history and those without. After exclusion criteria, patients with adequate angiographic monitoring and data were included in the study.

A total of 210 patients, 48 with a history of COVID-19, were included in the study. The mean age was ±55 10 years, and 122 (58%) patients were women. In patients with a history of COVID-19, TFC was significantly higher in the LAD (p < 0.001) and LCx (p < 0.001) arteries and RCA TFC (p = 0.223) was similar in both groups. In the linear mix model, male gender (β = 2.38, 95% CI = 1.26-3.51, p < 0.001) and history of COVID-19 (β = 1.51, 95% CI = 0.49-2.53, p = 0.004) were significantly associated with TFC.

TFC may be elevated due to coronary microvascular dysfunction in patients with a history of COVID-19.

Many articles on COVID19 deaths have been published since the pandemic has occurred. On reviewing the articles published until June 2021, the findings were very heterogeneous. Adding to the existing knowledge, there were also some unique observations made in the pathogenesis of COVID19. This review was done to determine the findings obtained and inferences drawn from various studies published globally among patients who died due to COVID19. PRISMA guidelines were used to conduct this systematic review. A search of databases like PubMed, ScienceDirect and Epistemonikos was done. The articles focusing on postmortem sample studies involving full autopsies, minimally invasive autopsies and tissue biopsy studies were screened and searched. The studies included were all the case reports, case series, narrative reviews and systematic reviews obtained in full text and in the English language containing study information, and samples obtained postmortem. The information obtained was tabulated using Microsoft excel sheets. The duplicates were removed at the beginning of the tabulation. Zotero referencing software was used for article sorting and citation and bibliography. Two authors independently reviewed the articles throughout the process to prevent bias. Adding to the heterogeneity of COVID19, the concept of lethality in preexisting disease conditions, the occurrence of secondary bacterial and fungal infections, and other pathogenetic mechanisms uniquely encountered are to be considered in treating the patients. Also, the presence of SARS-CoV-2 postmortem is established and should be considered a hazard.

Clinical and molecular heterogeneity are common features of human disease. Understanding the basis for heterogeneity has led to major advances in therapy for many cancers and pulmonary diseases such as cystic fibrosis and asthma. Although heterogeneity of risk factors, disease severity, and outcomes in survivors are common features of the acute respiratory distress syndrome (ARDS), many challenges exist in understanding the clinical and molecular basis for disease heterogeneity and using heterogeneity to tailor therapy for individual patients. This report summarizes the proceedings of the 2021 Aspen Lung Conference, which was organized to review key issues related to understanding clinical and molecular heterogeneity in ARDS. The goals were to review new information about ARDS phenotypes, to explore multicellular and multisystem mechanisms responsible for heterogeneity, and to review how best to account for clinical and molecular heterogeneity in clinical trial design and assessment of outcomes. The report concludes with recommendations for future research to understand the clinical and basic mechanisms underlying heterogeneity in ARDS to advance the development of new treatments for this life-threatening critical illness.