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This prospective, randomized, controlled clinical trial assessed the therapeutic effects of major ozone autohemotherapy (O 3 -MAH) in patients with post-acute sequelae of COVID-19 (PASC). Seventy-three eligible participants were randomly assigned to an O 3 -MAH plus conventional therapy group (n = 35) or a conventional therapy alone group (n = 38). Symptom score, pulmonary function, 6-minute walk distance (6MWD), and hematological, biochemical, and immunological parameters were evaluated before and after the interventions. Both groups demonstrated improvements in various parameters post-intervention, but efficacy was greater in the O 3 -MAH group than the conventional treatment group; with intervention effectiveness defined as a ≥ 50 % reduction in symptom score, 25 of 35 patients (71 %) responded to O 3 -MAH, while 17/38 patients (45 %) responded to conventional treatment alone (P = 0.0325). Significant improvements in symptom scores (P = 0.0478), tidal volume (P = 0.0374), predicted 6MWD (P = 0.0032), and coagulation and inflammatory indicators were noted in the O 3 -MAH group compared with the conventional treatment group. O 3 -MAH was more likely to be effective in patients with elevated CRP levels. Furthermore, O 3 -MAH markedly improved cellular immunity, and this improvement became more pronounced with extended treatment duration. In summary, combining O 3 -MAH with conventional treatment was more effective than conventional therapy alone in improving symptoms, pulmonary function, inflammation, coagulation, and cellular immunity in patients with PASC. Further research is now warranted to validate these findings and individualize the regimen., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Persistent post-COVID olfactory dysfunction continues to be studied due to the controversy in its pathophysiology and neuroimaging., Materials and Methods: The patients had confirmed mild COVID-19 infection with olfactory dysfunction of more than one month of evolution and they were compared to controls with normal olfaction, assessed using the Sniffin' Sticks Olfactory Test and underwent brain, magnetic resonance imaging (MRI) of the olfactory bulb and olfactory function., Results: A total of 8 patients and 2 controls participated. The average age of the patients was 34.5 years (SD 8.5), and that of the controls was 28.5 (SD 2.1). The average score in the patients' olfactory test was 7.9 points (SD 2.2). In brain and olfactory bulb MRI tests, no morphological differences were found. When evaluated by functional MRI, none of the patients activated the entorhinal area in comparison to the controls, who did show activation at this level. Activation of secondary olfactory areas in cases and controls were as follows: orbitofrontal (25% vs 100%), basal ganglia (25% vs 50%) and insula (38% vs 0%) respectively., Conclusions: There were no observed morphological changes in the brain MRI. Unlike the controls, none of the patients activated the entorhinal cortex in the olfactory functional MRI., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Background: Prone positioning (PP) has demonstrated its potential for improving outcomes in patients with ARDS who require invasive mechanical ventilation. However, the ability of prolonged proning to reduce mortality in patients with COVID-19 specifically, sessions lasting > 24 h remains uncertain., Methods: In this retrospective cohort study, we examined 158 subjects with COVID-19 pneumonia who required mechanical ventilation due to moderate-to-severe ARDS. Seventy-six subjects were placed in standard PP and 82 in extended PP, defined as prone sessions lasting at least 32 h. Our primary aim was to evaluate the effect of EPP on 90-d survival in subjects with COVID-19 with acute severe respiratory failure. To ensure the reliability of our findings and to minimize bias, we applied 3 adjustment approaches: cardinality matching (CM), matching weighting (MW), and inverse probability of treatment weighting with stabilized and trimmed weights (SW). We used Kaplan-Meier curves and Cox proportional hazard models to analyze the effects of EPP on 90-d mortality and sensitivity analysis by calculating E-values., Results: The overall crude 90-d mortality rate was 31.7%. The unadjusted 90-d mortality rates were 19.5% in the EPP group and 44.7% in the SPP group (hazard ratio [HR] 0.35 [95% CI 0.19- 0.63], P < .001). After adjustment for confounding factors using CM, MW, and SW, baseline covariates were balanced between the 2 groups. Subjects in the EPP group exhibited lower 90-d mortality rates after adjustment using CM (HR 0.42 [95% CI 0.23-0.79], P = .007), MW (HR 0.45 [95% CI 0.21-0.95], P = .036), or SW (HR 0.29 [95% CI 0.15-0.56], P < .001)., Conclusions: Extended PP was associated with improved 90-d survival in subjects with COVID-19 undergoing mechanical ventilation for severe ARDS. These findings suggest the potential benefit of EPP in the management of COVID-19-related respiratory failure. Further research and prospective studies are warranted to confirm and elucidate the underlying mechanisms of this association., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and RNA debris persist in viral reservoirs for weeks to months following infection, potentially triggering interferon production and chronic inflammation. RSLV-132 is a biologic drug composed of catalytically active human RNase1 fused to human IgG1 Fc and is designed to remain in circulation and digest extracellular RNA. We hypothesized that removal of SARS-CoV-2 viral RNA from latent reservoirs may improve inflammation, neuroinflammation, and fatigue associated with post-acute sequelae of SARS-CoV-2 infection (PASC)., Methods: This was a phase 2, double-blind, placebo-controlled randomized clinical trial in participants with a 24-week history of PASC and severe fatigue. The primary endpoint of the trial assessed the impact of 6 intravenous doses of RSLV-132 on the mean change from baseline at day 71 in the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS Fatigue SF 7a)., Results: A statistically significant difference on day 71 was not observed with respect to the primary or secondary endpoints. This was likely due to a placebo response that increased during the trial. Statistically significant improvement in fatigue as measured by the PROMIS Fatigue SF 7a, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and Physicians Global Assessment (PGA) instruments were observed earlier in the trial, with women demonstrating greater responses to RSLV-132 than men., Conclusion: While fatigue was not statistically significantly improved at Day 71, earlier timepoints revealed statistically significant improvement in fatigue and physician global assessment. The data suggest eliminating latent viral RNA by increasing serum RNase activity may improve fatigue in PASC patients. Women may respond better to this approach than men. Future studies will aim to confirm these findings., Competing Interests: Potential conflicts of interest. J. A. P. owns equity in Resolve Therapeutics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

BACKGROUND Coronavirus disease (COVID-19) can cause various complications. We report a case of severe COVID-19 acute respiratory distress syndrome (ARDS) in a patient receiving veno-venous extracorporeal membrane oxygenation (V-V ECMO), complicated by Guillain-Barre syndrome (GBS) and cerebral infarction, as well as pulmonary embolism. CASE REPORT A 55-year-old Japanese man with a history of ulcerative colitis was admitted for COVID-19. His respiratory status worsened and progressed to ARDS, requiring intubation on hospital day (HD) 3. On HD 16, contrast computed tomography revealed PE. On HD 18, his respiratory condition worsened, and V-V ECMO was initiated. On HD 23, V-V ECMO was successfully discontinued. He regained consciousness on HD 44, but he had quadriplegia. Deep-tendon reflexes were absent in all limbs. Cranial nerve involvement, specifically bilateral facial nerve weakness, was noted. Magnetic resonance imaging showed bilateral scattered cerebral infarctions on HD 76. Nerve conduction studies indicated severe axonal neuropathy. Cerebrospinal fluid examination showed albuminocytologic dissociation. The antibody to the ganglioside GD1a was positive. These findings were consistent with the diagnosis of GBS. He received immunoglobulin treatment on HD 89, and his neurological findings slightly improved. CONCLUSIONS This study emphasized that in COVID-19, neurological complications are not rare, are difficult to diagnose, and are prone to delays in detection.

Objectives: After acute coronavirus disease-2019 (COVID-19), people often experience fatigue, "brain fog," or other central neurologic symptoms (neuro-post-acute SARS-CoV2, or "Neuro-PASC"). In this observational study we evaluated whether abnormalities noted on initial evaluation persist after at least another year., Methods: Neuro-PASC research participants who had undergone comprehensive inpatient testing at the NIH Clinical Center returned after at least 1 year for follow-up assessments including symptoms rating scales, MRI, lumbar puncture for tests of the CSF, physiologic recordings during the Valsalva maneuver and head-up tilting (with serial plasma catechols and cardiac Doppler ultrasound during the tilting), blood volume measurement, skin biopsies to examine sympathetic innervation, and blood sampling for neuroendocrine and immunologic measures., Results: 7 patients with Neuro-PASC (6 women, age range 42-63 years) underwent follow-up testing. 71% of initially abnormal test results remained abnormal at follow-up, including the pattern of CSF and serum oligoclonal bands, CSF indices of central catecholamine deficiency, baroreflex-cardiovagal dysfunction, the occurrence of tilt-evoked sudden hypotension, white matter hyperintensities on MRI, and adaptive responses in CSF., Discussion: In Neuro-PASC most of the autonomic and immunologic abnormalities found initially are still present after more than a year.

Acute respiratory distress syndrome is a significant complication in critical care patients. COVID-19 (C19)-associated severe respiratory failure is related to it, and d-dimer rise predicts a worse outcome. To investigate the association between d-dimer and the severity of this respiratory syndrome, we conducted a study in C19 intubated patients. A retrospective, single-center observational study was conducted with 64 C19 adult intubated patients. Strata of d-dimer results between patients was evaluated using survival analysis. Survival was higher in mild respiratory distress patients. D-dimer showed poor sensitivity and specificity in predicting respiratory failure severity. Risk assessment for death showed a higher prevalence of admission d-dimer results (HR 1.335; 95% CI 0.695-2.564). Our sample confidently represented the medical profile of C19 severe patients. Sepsis development in C19 is associated with the inflammatory storm in respiratory distress syndrome. As the receiver operating curves show, the increase in d-dimer results is consistent with inflammation rather than a prognostic biomarker. As expected, severe respiratory distress patients presented higher mortality. In summary, d-dimer results are not associated with the prognosis of C19 respiratory distress syndrome patients.

Objective: This cross-sectional study aimed to compare oral manifestations between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-positive and SARS-CoV-2-negative patients and to examine associations between oral symptoms, Ct values of E and N SARS-CoV-2 viral genes, and the implications of low Ct values indicating a high viral load, which is a predictive factor for the outcome of COVID-19., Methods: A total of 353 participating patients were aged ≥18 years with clinical manifestations of COVID-19 infection and tested for SARS-CoV-2 carriage at the medical center, by reverse transcriptase polymerase chain reaction (RT-PCR). All patients filled out an anonymous digital questionnaire regarding oral and general symptoms and overall medical health.  Results: A significant association was found between SARS-CoV-2 carriage and dry mouth, unpleasant taste and changes in taste (p < 0.001); for example, 37.4% of the 147 SARS-CoV-2- positive participants had a dry mouth, compared to 18.9% of the 206 SARS-CoV-2- negative participants. Oral blisters were experienced by patients with an E gene Ct value of 10-20 (50%) or 21-30 (50%) (p = 0.041). Bad breath, dry mouth, unpleasant taste and changes in taste were mostly present in participants whose Ct values of both E and N genes were between 21 and 30.  Conclusions: This study found significant associations between low Ct values of E and N SARS-CoV-2 viral genes and high viral load, indicating that Ct values can serve as predictive factors for COVID-19 outcomes. The findings suggest that while oral symptoms are present, the Ct values and associated high viral loads are more critical indicators of disease severity and prognosis.

Angiotensin-converting enzyme 2 receptors (ACE2R) are requisite to enter the host cells for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). ACE2R is constitutive and functions as a type I transmembrane metallo-carboxypeptidase in the renin-angiotensin system (RAS). On thyroid follicular cells, ACE2R allows SARS-CoV-2 to invade the thyroid gland, impose cytopathic effects and produce endocrine abnormalities, including stiff back, neck pain, muscle ache, lethargy, and enlarged, inflamed thyroid gland in COVID-19 patients. Further damage is perpetuated by the sudden bursts of pro-inflammatory cytokines, which is suggestive of a life-threatening syndrome known as a "cytokine storm". IL-1β, IL-6, IFN-γ, and TNF-α are identified as the key orchestrators of the cytokine storm. These inflammatory mediators upregulate transcriptional turnover of nuclear factor-kappa B (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and mitogen-activated protein kinase (MAPK), paving the pathway for cytokine storm-induced thyroid dysfunctions including euthyroid sick syndrome, autoimmune thyroid diseases, and thyrotoxicosis in COVID-19 patients. Targeted therapies with corticosteroids (dexamethasone), JAK inhibitor (baricitinib), nucleotide analogue (remdesivir) and N-acetyl-cysteine have demonstrated effectiveness in terms of attenuating the severity and frequency of cytokine storm-induced thyroid dysfunctions, morbidity and mortality in severe COVID-19 patients. Here, we review the pathogenesis of cytokine storms and the mechanisms and pathways that establish the connection between thyroid disorder and COVID-19. Moreover, cross-talk interactions of signalling pathways and therapeutic strategies to address COVID-19-associated thyroid diseases are also discussed herein., Competing Interests: The authors report no conflict of interest for the present paper., (© 2024 Attiq et al.)

Rationale: This article reports a case of coronavirus disease (COVID-19)-associated autoimmune encephalitis (AE) and reviews the relevant literature to investigate the clinical manifestations, auxiliary inspection, diagnosis and treatment, and prognosis of AE associated with COVID-19., Patient Concerns: A 68-year-old female with fatigue developed altered consciousness after 2 days of fever, thereafter testing positive for COVID-19. The protein levels in the lumbar puncture cerebrospinal fluid were elevated, and cranial magnetic resonance imaging (MRI) scan indicated T2-weighted hyperintensity in the temporal lobe., Diagnoses: The patient was diagnosed with COVID-19-associated AE., Interventions: After admission, the patient received pulse steroid therapy with methylprednisolone. Additionally, gastric protection, blood glucose control, nutritional support, and other treatments were administered., Outcomes: The symptoms were significantly relieved by steroid pulse therapy. At the 3-month follow-up, the patient had recovered completely without any obvious discomfort., Lessons: The possibility of AE should be considered if neurological symptoms occur a few days after infection with COVID-19, with early diagnosis and immediate steroid pulse therapy resulting in better outcomes., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Diabetes Mellitus is a major predictor for severity and mortality that is increased by 50% in COVID-19 infection. The aim of this study is to estimate the prevalence of new-onset DM among patients with COVID-19 and examined the short clinical outcomes of the disease., Method: This is a retrospective study of revising electronic medical records to assess the prevalence of new-onset DM in COVID-19 patients and its impact on the severity of the disease. Adult patients with confirmed COVID-19 during the period from June 2020 to December 2021 were enrolled., Results: 725 patients were included. 53.8% of them were males and 46.2 were females, the mean age was 43.35 ± 16.76. 13.2% were diabetics; 2.2% with preexisting DM and 11.0% had new-onset DM. 6.34% had coexisting medical conditions. DKA at presentation was observed in 6 patients (0.8%) of newly diagnosed DM. There is a significant correlation between age and family history (FH), and BMI and new-onset DM (P < 0.05). The overall mortality rate was 2.2%, and it was significantly higher in diabetics in comparison to non-diabetics (P < 0.001). 8.6% had persistent hyperglycemia after 4 months of follow-up., Conclusion: The prevalence of COVID-19 related new-onset DM was correlated significantly with disease severity and mortality rate. Age, FH, and BMI, were the major predictors. We recommend that frequent monitoring of blood glucose for patients with COVID-19 infections to detect DM, therefore, prompt treatment can be initiated., (© 2024. The Author(s).)

Co-infection with diverse bacteria is commonly seen in patients infected with the novel coronavirus, SARS-CoV-2. This type of co-infection significantly impacts the occurrence and development of novel coronavirus infection. Bacterial co-pathogens are typically identified in the respiratory system and blood culture, which complicates the diagnosis, treatment, and prognosis of COVID-19, and even exacerbates the severity of disease symptoms and increases mortality rates. However, the status and impact of bacterial co-infections during the COVID-19 pandemic have not been properly studied. Recently, the amount of literature on the co-infection of SARS-CoV-2 and bacteria has gradually increased, enabling a comprehensive discussion on this type of co-infection. In this study, we focus on bacterial infections in the respiratory system and blood of patients with COVID-19 because these infection types significantly affect the severity and mortality of COVID-19. Furthermore, the progression of COVID-19 has markedly elevated the antimicrobial resistance among specific bacteria, such as Klebsiella pneumoniae , in clinical settings including intensive care units (ICUs). Grasping these resistance patterns is pivotal for the optimal utilization and stewardship of antibiotics, including fluoroquinolones. Our study offers insights into these aspects and serves as a fundamental basis for devising effective therapeutic strategies. We primarily sourced our articles from PubMed, ScienceDirect, Scopus, and Google Scholar. We queried these databases using specific search terms related to COVID-19 and its co-infections with bacteria or fungi, and selectively chose relevant articles for inclusion in our review., Competing Interests: The authors declare that they have no competing interests., (© 2024 Liu et al.)

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children., (© 2024. The Author(s).)

Background: COVID-19 patients may exhibit neurological symptoms due to direct viral damage, systemic inflammatory syndrome, or treatment side effects. Mechanical ventilation in patients with severe respiratory failure often requires sedation and neuromuscular blockade, hindering thorough clinical examinations. This study aimed to investigate neurological involvement through clinical and noninvasive techniques and to detect signs of intracranial hypertension in these patients., Method: We conducted a prospective observational study on mechanically ventilated COVID-19 adult patients admitted to our ICU, following standard of care protocols for ventilation and permissive hypercapnia. Data were collected at three time points: admission day (T1), day seven (T7), and day fourteen (T14). At each time point, patients underwent multimodal noninvasive neurological monitoring, including clinical examination, pupillary reactivity, transcranial color doppler of the middle cerebral artery (MCA), and optic nerve sheath diameter (ONSD) assessed via ultrasound (US). Head computer tomography (CT) was performed at T1 and T14. A limited subset of patients had a follow-up examination six months after ICU discharge., Results: Seventy-nine patients were recruited; most were under deep sedation and neuromuscular blockade at T1. Pupillary size, symmetry, and reactivity were normal, as was the MCA mean velocity. However, ONSD, assessed by both US and CT, appeared enlarged, suggesting raised intracranial pressure (ICP). In a subgroup of 12 patients, increased minute ventilation was associated with a significant decrease in US-ONSD, corresponding to a drop in paCO2. At follow-up, twelve patients showed no long-term neurological sequelae, and US-ONSD was decreased in all of them., Discussion and Conclusions: In this cohort, enlarged ONSD was detected during non-invasive neurological monitoring, suggesting a raised ICP, with hypercapnia playing a prominent role. Further studies are needed to explore ONSD behavior in other samples of mechanically ventilated, hypercapnic patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Carbonara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, we report a preanalytical challenge noted in our laboratory on plasma samples from a critically ill COVID-19 patient treated with hydroxychloroquine. This is significant because, in critically ill COVID-19 patients on hydroxychloroquine, plasma samples can have a high measured haemolysis index in the absence of haemolysis, with the impact on reporting the results for potassium and other analytes., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In this article, we describe the case of a 70-year-old man whose diagnosis of a brain meningioma was hindered by a SARS-CoV-2 infection. The patient, who had been vaccinated twice with the AstraZeneca COVID-19 vaccine, was admitted to Temporary Hospital No. 2, University Hospital (Białystok, Poland) with a positive PCR test result for SARS-CoV-2. The patient's general condition was good, but he reported a significant reduction in visual acuity in his left eye and headaches. A series of ophthalmological examinations were conducted, but they did not clarify the cause of the significant decrease in visual acuity. During hospitalization, an abnormal light reaction of the left pupil was observed, which led to the expansion of diagnostics to include imaging studies (CT and MRI). Computed tomography and magnetic resonance imaging revealed extensive isointense areas in the anterior cranial fossa, suggesting the presence of a meningioma. The final diagnosis and clarification of the cause of the visual impairment in the left eye resulted in the patient being transferred to the neurosurgery department for surgical treatment. COVID-19 diagnosis may mask the correct interpretation of other disease symptoms. Accidentally detected asymptomatic SARS-CoV-2 infection accelerated proper ophthalmic and neurology diagnosis. In this article, we describe the case of a 70-year-old man whose diagnosis of a brain meningioma was hindered by a SARS-CoV-2 infection. The patient, who had been vaccinated twice with the AstraZeneca COVID-19 vaccine, was admitted to Temporary Hospital No. 2, University Hospital (Białystok, Poland) with a positive PCR test result for SARS-CoV-2. The patient's general condition was good, but he reported a significant reduction in visual acuity in his left eye and headaches. A series of ophthalmological examinations were conducted, but they did not clarify the cause of the significant decrease in visual acuity. During hospitalization, an abnormal light reaction of the left pupil was observed, which led to the expansion of diagnostics to include imaging studies (CT and MRI). Computed tomography and magnetic resonance imaging revealed extensive isointense areas in the anterior cranial fossa, suggesting the presence of a meningioma. The final diagnosis and clarification of the cause of the visual impairment in the left eye resulted in the patient being transferred to the neurosurgery department for surgical treatment. COVID-19 diagnosis may mask the correct interpretation of other disease symptoms. Accidentally detected asymptomatic SARS-CoV-2 infection accelerated proper ophthalmic and neurology diagnosis.

Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), also known as post-COVID-19 condition or post-COVID syndrome, can affect anyone infected with SARS-CoV-2, regardless of age or the severity of the initial symptoms of COVID-19. Long COVID/PASC is the continuation or development of new symptoms after three months from the initial SARS-CoV-2 infection, which lasts for at least two months and has no other identifiable cause. Long COVID/PASC occurs in 10-20% of patients infected with SARS-CoV-2. The most common symptoms include fatigue, cognitive impairment (brain fog), and shortness of breath. However, more than 200 symptoms have been reported. No phenotypic or diagnostic biomarkers have been identified for developing long COVID/PASC, which is a multisystem disorder that can present with isolated or combined respiratory, hematological, immunological, cardiovascular, and neuropsychiatric symptoms. There is no cure. Therefore, individualized patient management requires a multidisciplinary clinical approach. Because millions of people have had and continue to have COVID-19, even in the era of vaccination and antiviral therapies, long COVID/PASC is now and will increasingly become a health and economic burden that the world must prepare for. Almost five years from the beginning of the COVID-19 pandemic, this article aims to review what is currently known about long COVID/PASC, the anticipated increasing global health burden, and why there is still an urgent need to identify diagnostic biomarkers and risk factors to improve prevention and treatment.

Introduction: COVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin., Methods: This retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed., Results: 10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39])., Conclusions: Findings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: The impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC) remains uncertain given the lack of sufficient evidence., Aim: To investigate the impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC)., Methods: Patients who were pathologically diagnosed with HCC and underwent elective partial hepatectomy in Guangdong Provincial People's Hospital between January 2022 and April 2023 were enrolled in this retrospective cohort study. The patients were divided into two groups based on their history of SARS-CoV-2 infection. Rehabilitation parameters, including postoperative liver function, incidence of complications, and hospitalization expenses, were compared between the two groups. Propensity score matching (PSM) was performed to reduce confounding bias., Results: We included 172 patients (58 with and 114 without prior SARS-CoV-2 infection) who underwent liver resection for HCC. No significant differences in the rehabilitation parameters were observed between the two groups. After PSM, 58 patients were selected from each group to form the new comparative groups. Similar results were obtained within the population after PSM., Conclusion: Prior SARS-CoV-2 infection does not appear to affect postoperative rehabilitation, including liver function, postoperative complications, or hospitalization expenses among patients with HCC after elective partial hepatectomy., (© 2024. The Author(s).)

Population studies have suggested that viral infections may be contributing to risk of ischemic stroke, although the mechanisms for this are unclear. In this review, we examine the epidemiological evidence supporting the involvement of viral diseases, including influenza, COVID-19, chronic herpesvirus infections, and hepatitis C in current trends of stroke incidence. To support these associations, we highlight the virus-host interactions that are critical in the context of stroke, including direct effects of acute and persistent viral infections on vascular function, inflammation, and thrombosis. Additionally, we evaluate the systemic changes that occur during viral infection that can predispose individuals to ischemic stroke, including alterations in blood pressure regulation, coagulation, and lipid metabolism. Our review emphasizes the need to further elucidate precise mechanisms involved in viral infections and stroke risk. Future research will inform the development of targeted interventions for stroke prevention in the context of viral diseases.

Background: Multisystem inflammatory syndrome associated to Covid-19 (MIS-C) is one of the most severe outcomes of SARS-CoV-2 in children. Covid-19 vaccines were successfully implemented in Chile for the pediatric population since 2021, using both mRNA and inactivated platforms. Effectiveness against MIS-C has been reported for mRNA vaccines. The aim of this study was to describe the epidemiologic trend of MIS-C in Chile during Covid-19 pandemic, both before and after the availability of vaccination for children., Materials and Methods: Analytic study of MIS-C cases from April 2020 to December 2022. Epidemiological data, SARS-CoV-2 variants and vaccination uptake information were obtained from the Epidemiology Department-Ministry of Health, Institute of Public Health and the National Immunization Program, respectively., Results: 496 cases of MIS-C were reported, 58 % males. Median age was 5 years and most frequent age-cohorts were 6-11 and 0-2 years old with a 33 % each. After the introduction of the Covid-19 vaccine, most cases occurred in children aged 0-2 years. Incidence rates were 3.8, 5.4 and 1.7 per 100,000 inhabitants in 2020, 2021 and 2022, respectively. 97 % of cases (481) occurred in unvaccinated subjects. On those previously vaccinated (15), all but one case occurred in children receiving the inactivated vaccine. No association among circulating variants and incidence was observed. Incidence rate reduction (IRR) comparison between 2020 and 2021-2022 periods was 0.72 (CI 95 % 0.65-0.81, p < 0.05) overall; 0.86 for 0-2 years (CI 95 %:0.71-1; p = 0.12); 0.88 for 3-5 years (CI 95 %:0.69-1.11; p = 0.28); 0.61 for 6-11 years (CI 95 %: 0.50-0.75; p < 0.05); and 0.64 for 12-17 years (CI 95 %:0.47-0.89; p < 0.05), consistent with vaccination uptake during the studied period: 63 % for 3-5 years, 91 % for 6-11 years, and 99 % for 12-17 years., Conclusions: A decline of MIS-C incidence and a shift to younger, unvaccinated population overtime was observed. IRR decreased in age-cohorts which achieved high vaccination rates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rodolfo Villena reports a relationship with Sinovac Biotech Ltd that includes: funding grants. Rodolfo Villena reports a relationship with Pfizer that includes: speaking and lecture fees. Rodolfo Villena reports a relationship with Janssen Pharmaceuticals Inc that includes: funding grants. Giannina Izquierdo reports a relationship with Pfizer Inc that includes: speaking and lecture fees. Juan Pablo Torres reports a relationship with Pfizer that includes: speaking and lecture fees If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: In addition to physical symptoms such as dyspnea, fatigue, post-exertional malaise, and pain, a subgroup of patients with Post-COVID-19 syndrome (Post-Acute Sequelae of COVID-19, PASC) suffers from mental illnesses such as anxiety, depression, and neurocognitive impairments. To date, there are no causal treatments available for PASC. While initial studies show that psychotherapy improves psychological symptoms, PASC-related fatigue, and psychosocial functioning, further research is needed to evaluate the effectiveness of psychotherapeutic treatment for PASC., Methods and Analysis: This study presents a non-randomized controlled trial aimed at evaluating the effectiveness of a five-week multimodal inpatient psychosomatic treatment program for individuals experiencing PASC symptoms and comorbid mental illness. A total of 118 patients presented at the Post-COVID Center at the Universitätsklinikum Erlangen will be assigned to the intervention group receiving inpatient psychosomatic treatment or the control group receiving treatment as usual. The inclusion criteria for the intervention group are a diagnosis of PASC and at least one condition of mental distress and problems with coping with illness. The primary objective of the intervention is to reduce mental ailments, including depression and anxiety, as well as neurocognitive deficits, and to address PASC symptoms such as fatigue and pain. The core elements of the treatment are psychotherapy in individual and group settings, medical treatment, neurocognitive training, and physical therapy, adapted to the individual's capacity and oriented towards the concept of pacing. After enrollment, participants will undergo a 6-month follow-up to assess long-term results and the sustainability of the intervention effects., Discussion: This study examines the effectiveness of inpatient psychotherapeutic treatment in PASC patients with comorbid mental illness in comparison with a control group based on treatment as usual. The results of the study can contribute to the development of evidence-based interventions to address the complex needs of patients with PASC and comorbid mental illness., Trial Registration: German Clinical Trial Register (DRKS), retrospectively registered 15.02.2024 DRKSID DRKS00033562., (© 2024. The Author(s).)

Objective: Obesity and type 2 diabetes (DM) are risk factors for severe coronavirus disease 2019 (COVID-19) outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with overweight/obesity (Ov/Ob, BMI ≥ 23 kg/m2) and DM in Bangladesh., Methods: In this cross-sectional study, SARS-CoV-2-specific antibody and T-cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020., Results: In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T-cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, Ov/Ob was associated with decreased neutralizing antibody titers, and increased SARS-CoV-2 spike-specific IFN-γ response along with increased proliferation and IL-2 production by CD8 + T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T-cell responses after adjustment for obesity and other confounders., Conclusion: Ov/Ob is associated with lower neutralizing antibody levels and higher T-cell responses to SARS-CoV-2 post-COVID-19 recovery, while antibody or T-cell responses remain unaltered in DM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology.)

Although endothelial damage has been hypothesized to be associated with coronavirus disease 2019 (COVID-19)-related cerebral infarction based on the specificity of the viral cellular invasion pathway, no case has been reported to date. We herein report a 51-year-old Japanese woman who presented with neck pain one week after COVID-19 infection. Computed tomography and magnetic resonance imaging revealed inflammation of the carotid and vertebral arteries. Ultrasonography revealed multiple flap-like structures that were assumed to be thrombi. Although the patient had no cerebral infarction, this could be an important case of vascular damage and thrombus formation in a COVID-19 patient.

Aims: Many studies evaluated the functional response in post-Covid-19 patients; however, they systematically excluded patients with concomitant acute coronary syndrome (ACS). We evaluated the long-term functional capacity assessed by cardiopulmonary exercise test (CPET) in patients hospitalized for ACS and concomitant SARS-CoV2 infection. The secondary aim was to investigate the functional response in patients with symptoms related to "long COVID-19 syndrome" (LCS)., Methods: This cross-sectional case-control study compared 20 patients with ACS and concomitant SARS-COV2 infection with 20 patients without COVID-19. At the follow-up visit (between 6 and 12 months after revascularization procedure) all patients underwent a CPET., Results: Patients with previous ACS and concomitant COVID-19 showed a reduced O2 consumption than controls (predicted peak V̇O2 74.00% vs 86.70%; p = 0.01) with a high degree of ventilatory inefficiency (VE/ V̇CO2 slope 38.04 vs 30.31; p = 0.002). 50% of subjects with previous COVID-19 disease showed symptoms related to "LCS"; this subgroup demarcates the characteristic reduced exercise capacity found in the entire COVID + group., Conclusions: This study is the first in literature having analyzed the long-term functional capacity phenotype in a population of ACS patients and concomitant SARS-CoV2 infection. Severe ventilatory inefficiency emerged as the functional signature of these patients. Moreover, the subset of patients with symptoms related to LCS has the most compromised long term reduced exercise capacity and an altered ventilation control., Competing Interests: Declaration of Competing Interest We declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Published by Elsevier B.V.)

To evaluate the efficiency of 5 screening questionnaires for obstructive sleep apnea (OSA), OSA frequency, and the association between OSA and COVID-19 severity in recent COVID-19 cases, and to compare the use of the oxygen desaturation index (ODI) as an alternative measure for the respiratory disturbance index (RDI). This open cohort study recruited patients with recent COVID-19 (within 30-180 days) diagnosed using reverse transcription polymerase chain reaction. Participants were screened for OSA using the following 5 sleep disorder questionnaires prior to undergoing type I polysomnography: the Sleep Apnea Clinical Score (SACS), Epworth Sleepiness Scale (ESS), STOP-Bang score, No-Apnea score, and Berlin questionnaire. Polysomnography revealed that 77.5% of the participants had OSA and that these patients exhibited higher COVID-19-related hospitalization (58%) than those exhibited by non-apneic patients. The Kappa coefficient showed reasonable agreement between RDI > 5/h and No-Apnea score, RDI > 15/h and Berlin questionnaire score, and Epworth Sleepiness Scale and STOP-Bang score, but only moderate agreement between RDI > 15/h and No-Apnea score. An OSA-positive No-Apnea score increased the specificity of the SACS to 100% when RDI > 5/h. The intraclass correlation coefficient showed 95.2% agreement between RDI > 5/h and ODI > 10/h. The sequential application of the No-Apnea score and SACS was the most efficient screening method for OSA, which had a moderately high incidence among the post-COVID-19 group. We demonstrated an association between OSA and COVID-19 related hospitalization and that ODI could be a simple method with good performance for diagnosing OSA in this population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: During the coronavirus disease of 2019 (COVID-19) pandemic, various movement disorders associated with COVID-19 infection have been reported. However, the incidence of dystonia specifically associated with COVID-19 infection has been particularly rare., Patient Concerns: A 43-year-old male patient presented to the movement disorders clinic with complaints of facial grimacing while chewing and experiencing spasms during nasal breathing. These symptoms appeared 2 weeks after he tested positive for COVID-19., Diagnoses: Based on normal diagnostic test results, including brain imaging and blood tests, it was concluded that task-specific facial dystonia following COVID-19 infection., Interventions: Despite treatment with clonazepam, trihexyphenidyl, and carbamazepine, his condition did not improve. Subsequently, botulinum toxin injections were administered to the affected facial muscles identified through video analysis., Outcomes: Botulinum toxin injections led to a significant improvement in the patient's symptoms., Lessons: Task-specific dystonia affecting the facial muscles, particularly induced by specific actions such as chewing and nasal breathing, is rare and may represent an atypical post-infectious manifestation of COVID-19., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The worldwide spread of coronavirus disease 2019 (COVID-19) has resulted in an unparalleled health emergency of global proportions. Around 31% of individuals with COVID-19 experience thrombosis associated with hypercoagulation. COVID-19 patients have shown an increase in platelet activation, but the mechanism has not been fully understood yet. One theory suggests that this could be related to the heparin-induced thrombocytopenia phenomenon, where platelet activation involves anti-PF4 antibodies that are associated with thrombosis. Vitamin D has been established to exert an influence on immunological responses and inflammation. The aim of this study is to analyze the correlation between serum 25-hydroxy-cholecalciferol [25(OH)D] levels and anti-PF4 antibodies among COVID-19 patients. A cross-sectional study was conducted among 160 COVID-19 patients at Cipto Mangunkusumo General Hospital and Wisma Atlit Hospital Jakarta from October 2021 to January 2022. The mean serum 25(OH)D level was 15.1 ng/mL. A significant negative correlation was found between serum 25(OH)D and anti-PF4 levels in mild COVID-19 patients (P = .035; R = -0.236). Remarkably, P-selectin levels were significantly higher in the moderate COVID-19 group compared to the severe group (P = .031). Serum 25(OH)D level had a significant negative correlation with anti-PF4 level in mild COVID-19 patients. Thus, it is highly recommended to ensure that serum 25(OH)D levels are maintained above 30 ng/mL. Remarkably, the P-selectin level was significantly higher in the moderate COVID-19 group compared to the severe group., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The COVID-19 pandemic has impacted the general population in different ways, including the vulnerable population of children with special needs.In this case report, we will discuss the emergence of a transient, full-blown picture of autism spectrum disorder (ASD) in a child who contracted a COVID-19 infection, and his gradual improvement over the course of a few months. This broadens our perspective on the possible neurocognitive clinical presentations of COVID-19 infection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

SETANTA (Study of HEarT DiseAse and ImmuNiTy After COVID-19 in Ireland) study aimed to investigate symptom burden and incidence of cardiac abnormalities after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/COVID-19 and to correlate these results with biomarkers of immunological response and coagulation. SETANTA was a prospective, single-arm observational cross-sectional study condcuted in a primary practice setting, and prospectively registered with ClinicalTrials.gov (identifier: NCT04823182). Patients with recent COVID-19 infection (≥ 6 weeks and ≤ 12 months) were prospectively enrolled. Primary outcomes of interest were markers of cardiac injury detected by cardiac magnetic resonance imaging (CMR), which included left ventricular ejection fraction, late gadolinium enhancement and pericardial abnormalities, as well as relevant biomarkers testing immunological response and coagulopathy. 100 patients (n = 129 approached) were included, amongst which 64% were female. Mean age of the total cohort was 45.2 years. The median (interquartile range) time interval between COVID-19 infection and enrolment was 189 [125, 246] days. 83% of participants had at least one persistent symptom, while 96% had positive serology for prior SARS-CoV-2 infection. Late gadolinium enhancement, pericardial effusion, was present in 2.2% and 8.3% respectively, while left ventricular ejection fraction was below the normal reference limit in 17.4% of patients. Von Willebrand factor antigen was elevated in 32.7% of patients and Fibrinogen and D-Dimer levels were found to be elevated in 10.2% and 11.1% of patients, respectively. In a cohort of primary practice patients recently recovered from SARS-CoV-2 infection, prevalence of persistent symptoms and markers of abnormal coagulation were high, despite a lower frequency of abnormalities on CMR compared with prior reports of patients assessed in a hospital setting.Trial Registration: Clinicaltrials.gov, NCT04823182 (prospectively registered on 30th March 2021)., (© 2024. The Author(s).)

Objectives: This study aims to describe the incidence, symptom clusters and determinants of post-acute COVID symptoms using data from the COVID RADAR app in the Netherlands., Design: Prospective cohort., Setting: General population in the Netherlands from April 2020 to February 2022., Participants: A total of 1478 COVID RADAR app users, with data spanning 40 days before to 100 days after positive SARS-CoV-2 test., Outcome Measures: Incidence and duration of 10 new symptoms that developed during acute infection, defined as 10 days prior and 10 days after positive test. Clustering of these post-acute COVID symptoms and associations between factors known in the acute phase and 100-day symptom persistence., Results: The most frequent post-acute symptoms were cough, loss of smell or taste and fatigue. At 100 days postinfection, 86 (8%) participants still experienced symptoms. Three post-acute COVID symptom clusters were identified: non-respiratory (headache and fatigue; 49% of participants with post-acute COVID symptoms); olfactory (15%) and respiratory (8%). Vaccination was associated with a lower risk of post-acute COVID symptoms 100 days after infection, although CIs were wide (OR: 0.5; 95% CI: 0.2 to 1.5), but not with non-respiratory symptoms (OR: 1.0; 95% CI: 0.3 to 4.4). Severe acute disease increased the risk of post-acute COVID symptoms (OR: 1.4; 95% CI: 1.2 to 1.5; per additional acute symptom)., Conclusions: In this cohort of infected community-dwelling app users, 5%-10% experienced post-acute COVID symptoms. The symptoms cluster in several distinct entities, which differ in incidence, patient characteristics and vaccination effects. This suggests multiple mechanisms underlying the development of post-acute COVID symptoms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: Liver function test (LFT) abnormalities are higher in patients with severe COVID-19. Most of the studies on this theme were conducted in foreign nations, and the association with LFT abnormalities was not sufficiently addressed in the study areas. Therefore, the current study aimed to investigate the effects of COVID-19 infection on liver function of patients., Setting: A facility-based comparative cross-sectional study was carried out from 10 April to 15 June 2022, among COVID-19 infected individuals admitted in Eka Kotebe General Hospital and Saint Petrous Specialized Hospitals, Addis Ababa, 2022., Participants: A total of 284 confirmed COVID-19-positive and COVID-19-negative controls matched by gender and age were included in the present study., Results: Among SARS-COV-2 positive groups, 63 (44.4%) had one or more LFT abnormalities. The most common elevated level of the LFTs among patients with COVID-19 were gamma-glutamyl transferase (GGT) 50 (35.2%), while the most common lowered level was albumin 58 (40.8%). The mean values of aspartate aminotransferase (AST) (35.4±26.9 vs 22.9±12.6, p<0.001) were significantly different between patients with COVID-19 and the COVID-19-free groups. Being COVID-19-positive was significantly associated with an elevated level of AST (AOR=3.0, 95% CI 1.2 to 7.4) and GGT (AOR=4.55, 95% CI 2.02 to 10.3). Being male was significantly associated with an elevated level of total bilirubin (BILT, AOR=2.41, 95% CI 1.2 to 4.9) and direct bilirubin (BILD, AOR=3.7, 95% CI 1.72 to 8.2), and also severe stage of COVID-19 was associated with hypoalbuminaemia (AOR=3.3, 95% CI 1.4 to 7.9). SARS-COV-2 infection was independently associated with LFT abnormality., Conclusion: Patients with COVID-19 had decreased albumin levels, and elevated AST, GGT, BILT and BILD levels., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Limited evidence exists regarding the link between coronavirus disease 2019 (COVID-19) and pneumothorax. Therefore, we aimed to evaluate the occurrence rate of pneumothorax in hospitalized patients with COVID-19 and compare the risk of pneumothorax between patients with COVID-19 and influenza. This retrospective cohort study used patient data from the National Health Insurance Service of South Korea. Patients diagnosed with COVID-19 (December 2019 to December 2021) and influenza (January 2019 to December 2021) who required hospitalization and respiratory support were included. We identified 46,460 patients with COVID-19 and 6,117 with influenza. The occurrence rate of pneumothorax was 0.74% in patients with COVID-19. In an inverse probability of treatment weighting matched cohort, the Cox proportional hazards regression model showed that COVID-19 was not associated with an increased risk of pneumothorax compared to influenza (hazard ratio, 1.22; 95% confidence interval, 0.75-1.99). However, the risk of pneumothorax associated with COVID-19 compared to influenza was significantly higher in patients without chronic lung disease than in those with (P for heterogeneity = 0.037). In conclusion, COVID-19, compared with influenza, is not associated with an increased risk of pneumothorax; however, it is associated with an increased risk in patients without chronic lung disease., (© 2024. The Author(s).)

Venous thromboembolism (VTE) is a common, deadly disease with an increasing incidence despite preventive efforts. Clinical observations have associated elevated antibody concentrations or antibody-based therapies with thrombotic events. However, how antibodies contribute to thrombosis is unknown. Here, we show that reduced blood flow enabled immunoglobulin M (IgM) to bind to FcμR and the polymeric immunoglobulin receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently, the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent IgG deposition. This leads to classical complement activation, setting in motion a prothrombotic vicious circle. Key elements of this mechanism were present in humans in the setting of venous stasis as well as in the dysregulated immunothrombosis of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically targeting complement. Hence, our results uncover antibodies as previously unrecognized central regulators of thrombosis. These findings carry relevance for therapeutic application of antibodies and open innovative avenues to target thrombosis without compromising hemostasis., Competing Interests: Declaration of interests C.Q.S. and A.D. are inventors of a patent application that describes the use of engineered proteins as potent complement regulators for therapeutic applications. C.Q.S. received honoraria for speaking at symposia organized by Alexion Pharmaceuticals and Swedish Orphan Biovitrum (Sobi). M.I. participates in advisory boards/consultantship for Asher Biotherapeutics, GentiBio, Clexio Biosciences, Sybilla Biotech, BlueJay Therapeutics, Bristol Myers Squibb, and Aligos Therapeutics and receives funding from Asher Biotherapeutics and VIR Biotechnology., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The mortality risk of co-infections/secondary infections (CoI/ScI) is under-reported in patients with non-critical COVID-19, leading to the under-management of CoI/ScI and publication bias in the medical literature. We aimed to investigate the association between CoI/ScI and mortality in patients hospitalised with mild-to-severe COVID-19., Methods: We conducted a retrospective cohort study at a COVID-19 treatment hospital in Vietnam and collected all eligible medical records, with CoI/ScI status as the exposure (non-CoI/ScI and CoI/ScI, with the latter including nature of pathogen [bacterial, fungal, or bacterial + fungal] and multidrug-resistance pathogen [no MDRp or ≥ 1 MDRp]). The outcome was all-cause mortality, defined as in-hospital death by all causes or being discharged under critical illness. We used time-dependent analysis to report rates of mortality with 95% confidence intervals (95% CI, Poisson regression) and hazard ratios (HR) with 95% CI (Cox proportional hazards regression with Holm's method for multiplicity control)., Results: We followed 1466 patients (median age 61, 56.4% being female) for a median of 9 days. We recorded 387 (26.4%) deaths (95/144 [66.0%] in the CoI/ScI group and 292/1322 [22.1%] in the non-CoI/ScI group). Adjusted mortality rates (per 100 person-days) of the CoI/ScI (6.4, 95% CI 5.3 to 7.8), including bacterial (8.0, 95% CI 7.2 to 8.9), no MDRp (5.9, 95% CI 4.8 to 7.4), and ≥ 1 MDRp (9.0, 95% CI 8.2 to 10.0) groups were higher than that of the non-CoI/ScI group (2.0, 95% CI 1.8 to 2.2). These corresponded to higher risks of mortality in the overall CoI/ScI (HR 3.27, 95% CI 2.58 to 4.13, adjusted p < 0.001), bacterial CoI/ScI (HR 3.79, 95% CI 2.97 to 4.83, adjusted p < 0.001), no MDRp CoI/ScI (HR 3.13, 95% CI 2.42 to 4.05, adjusted p < 0.001), and ≥ 1 MDRp CoI/ScI group (HR 3.89, 95% CI 2.44 to 6.21, adjusted p < 0.001). We could not attain reliable estimates for fungal and bacterial + fungal CoI/ScI., Conclusion: Compared with the non-CoI/ScI group, patients with CoI/ScI had a significantly higher risk of all-cause mortality, regardless of resistance status. More evidence is needed to confirm the mortality risks in patients with fungal or bacterial + fungal CoI/ScI., (© 2024. The Author(s).)

Although COVID-19 infection is an immunosuppressant disease, many immunosuppressant agents, such as pulse methylprednisolone (PMP), dexamethasone (DXM), and tocilizumab (TCZ), were used during the pandemic. Secondary infections in patients with COVID-19 have been reported recently. This study investigated these agents' effects on secondary infections and outcomes in patients with COVID-19 in intensive care units (ICUs). This study was designed retrospectively, and all data were collected from the tertiary intensive care units of six hospitals between March 2020 and October 2021. All patients were divided into three groups: Group I [GI, PMP (-), DXM (-) and TCZ (-)], Group II [GII, PMP (+), DXM (+)], and Group III [GIII, PMP (+), DXM (+), TCZ (+)]. Demographic data, P a O/FiO 2 ratio, laboratory parameters, culture results, and outcomes were recorded. To compare GI-GII and GI-GIII, propensity score matching (PSM) was used by matching 14 parameters. Four hundred twelve patients with COVID-19 in the ICU were included in the study. The number of patients with microorganisms ≥ 2 was 279 (67.7%). After PSM, in GII and GIII, the number of (+) tracheal cultures and (+) bloodstream cultures detected different microorganisms ≥ 2 during the ICU period, neuropathy, tracheotomized patients, duration of IMV, and length of ICU stay were significantly higher than GI. The mortality rate was similar in GI and GII, whereas it was significantly higher in GIII than in GI. The use of immunosuppressant agents in COVID-19 patients may lead to an increase in secondary infections. In addition, increased secondary infections may lead to prolonged ICU stay, prolonged IMV duration, and increased mortality., (© 2024. The Author(s).)

Background: Since the discovery of COVID-19 in December 2019, the novel virus has spread globally causing significant medical and socio-economic burden. Although the pandemic has been curtailed, the virus and its attendant complication live on. A major global concern is its adverse impact on male fertility., Aim: This study was aimed to give an up to date and robust data regarding the effect of COVID-19 on semen variables and male reproductive hormones., Materials and Methods: Literature search was performed according to the recommendations of PRISMA. Out of the 852 studies collected, only 40 were eligible for inclusion in assessing the effect SARS-CoV-2 exerts on semen quality and androgens. More so, a SWOT analysis was conducted., Results: The present study demonstrated that SARS-CoV-2 significantly reduced ejaculate volume, sperm count, concentration, viability, normal morphology, and total and progressive motility. Furthermore, SARS-CoV-2 led to a reduction in circulating testosterone level, but a rise in oestrogen, prolactin, and luteinizing hormone levels. These findings were associated with a decline in testosterone/luteinizing hormone ratio., Conclusions: The current study provides compelling evidence that SARS-CoV-2 may lower male fertility by reducing semen quality through a hormone-dependent mechanism; reduction in testosterone level and increase in oestrogen and prolactin levels., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 V. J. et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Coronavirus disease 2019 (COVID-19) caused by the coronavirus SARS-CoV-2, has emerged as a rapidly spreading contagious disease across the globe. Recent studies showed that people with diabetes mellitus, severe obesity, and cardiovascular disease are at higher risk of mortality from COVID-19. It has been suggested that the increased risk is due to the chronic inflammatory state associated with type 2 diabetes. This study aimed to evaluate the efficacy of pioglitazone, a strong insulin sensitizer with anti-inflammatory properties, in improving the clinical outcomes of patients with type 2 diabetes admitted with moderate-severe COVID-19., Method: We enrolled 350 patients with type 2 diabetes who were admitted to hospitals in Qatar and Kuwait with COVID-19. Patients were randomized to receive, in a double-blind fashion, pioglitazone ( n = 189) or a matching placebo ( n = 161) for 28 days. The study had two primary outcomes: (1) the incidence of a composite outcome composed of (a) the requirement for mechanical ventilation, (b) death, and (c) myocardial damage; and (2) an increase in C-reactive protein (CRP) levels., Results: The first primary outcome occurred in 28 participants (8%), and the secondary outcome occurred in 17. Treatment with pioglitazone showed a significant reduction in interleukin (IL)-3 levels compared with placebo treatment (mean (SD) 2.73 (± 2.14) [95% CI: 0.02, 1.1], p = 0.043 vs. 2.28 (± 1.67) [95% CI: - 0.23, 0.86], p = 0.3, respectively), with no effect seen in the levels of other inflammatory markers. Even though not significant, a few of the patients on pioglitazone exhibited serum troponin levels > 3 times higher than the normal range seen in patients on placebo. On the other hand, more patients on pioglitazone were admitted to the ICU than those with placebo, and no significant difference in the CRP reduction was observed between the two groups., Conclusion: The results of the present study demonstrate that pioglitazone treatment did not independently provide any additional clinical benefit to patients with type 2 diabetes admitted with a COVID-19 infection., Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04604223., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baagar, Alessa, Abu-Farha, Abubaker, Alhumaidi, Franco Ceruto, Hamad, Omrani, Abdelrahman, Zaka-Ul Haq, Safi, Alhariri, Barman, Abdelmajid, Cancio, Elmekaty, Al-Khairi, Cherian, Jayyousi, Ahmed, Qaddoumi, Hajji, Esmaeel, Al-Andaleeb, Channanath, Devarajan, Ali, Thanaraj, Al-Sabah, Al-Mulla, Abdul-Ghani and Jayyousi.)

The coronavirus disease 2019 (COVID-19) survivors are frequently observed to present persistent symptoms constituting what has been called "post-acute COVID-19 syndrome" (PACS) or "long COVID-19". Some clinical risk factors have been identified to be associated with PACS development; however, specific mechanisms responsible for PACS pathology remain unknown. This study investigates clinical, immunological, and metabolomic risk factors associated with post-acute COVID-19 syndrome (PACS) in 51 patients, assessed 7-19 months after acute infection. Among the participants, 62.7% were male and 37.2% were female, with an average age of 47.8 years. At the follow-up, 37.2% met the criteria for PACS, revealing significant differences in immunological and metabolomic profiles at the time of acute infection. Patients with PACS were characterized by elevated levels of mature low-density granulocytes (LDGs), interleukin-8 (IL-8), pyruvate, pseudouridine, and cystine. Baseline multivariate analysis showed increased pyruvate and decreased alpha tocopherol levels. At follow-up, there was a decrease in absolute B lymphocytes and an increase in non-classical monocytes and 3-hydroxyisovaleric acid levels. These findings suggest that specific immunological and metabolomic markers during acute infection can help identify patients at higher risk of developing persistent PACS.

Objective: To describe cases of acute kidney injury (AKI) in children diagnosed with COVID-19, associated risk factors, clinical aspects and outcome of cases., Methods: Retrospective study, carried out in a pediatric hospital between March 2020 and September 2021, with patients with COVID-19 who were diagnosed with AKI, studying information present in medical records such as comorbidities, age, gender and use of nephrotoxic medications., Results: We studied 40 cases, and male individuals were significantly more affected (62.5%; p=0.025). AKI was a severe complication of COVID-19 infection, with 100% of the sample requiring admission to the Intensive Care Unit and 22.5% dying. The most prevalent comorbidities analyzed in this study were epilepsy, cerebral palsy and heart disease. Most patients were classified according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria as KDIGO 1 (42.5%), and required orotracheal intubation (67.5%). The frequency of use of nephrotoxic medications and need for dialysis was low, with percentages of 35 and 17.5%, respectively. Among the children who died, 70.4% had some comorbidity and 88.8% received invasive ventilation., Conclusions: AKI in children with COVID-19 infection is associated with severe conditions. Despite the severity, most patients were discharged alive from the hospital.

Rationale: Pregnancy is a special term in life with physiological changes in both cardiorespiratory and immune systems; that is why severe acute respiratory syndrome coronavirus 2 infection in pregnancy may result in an altered response. With this, we present a case report of a young pregnant lady who was exposed to severe acute respiratory syndrome coronavirus 2 infection just before pregnancy and ended up with an affected fetus. The impact of coronavirus disease 2019 (COVID-19) exposure on neonatal outcomes has not yet been fully evaluated; by this article, we aim to find if COVID-19 exposure is linked to congenital anomalies., Patient Concerns: A 25-year-old woman who has no history of genetic or chronic diseases applied to our clinic for routine control of pregnancy. She does not have a consanguineous marriage or any other potential risk factors for pregnancy., Diagnoses and Interventions: She had a history of COVID-19 polymerase chain reaction positivity 2 days before the first day of the last menstruation period and hospitalization for 7 days. After 7 days of treatment with favipiravir and levofloxacin, enoxaparin sodium, famotidine, paracetamol, budesonide, dornaz alfa, and vitamin C; her general situation gets better, and discharged from the hospital on the seventh day of hospitalization without any further treatment prescription., Outcomes: During her routine controls for pregnancy at first-trimester evaluation ultrasonography; there was right forearm aplasia and deformities at both feet and legs., Lessons: In the literature, there is conflicting evidence about the impact of COVID-19 in pregnancy especially if the patient is confronted with the virus in the first trimester. Despite the increasing number of published studies on COVID-19 in pregnancy, there are insufficient good quality unbiased studies about the issue. Risk factors for COVID-19 overlap with the risk factors for pregnancy complications and the risk factors of the treatment prescribed. The impact of COVID-19 exposure on neonatal outcomes has not yet been fully evaluated; in this article, we aim to find if COVID-19 exposure is linked to congenital anomalies. Further research is needed to ascertain neonatal outcomes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Awake-prone position combined with noninvasive ventilation or high-flow nasal cannula ventilation has been shown to be safe in the treatment of patients with moderate to severe ARDS and COVID-19, and may avoid intubation and reduce patient mortality. We conducted a cross-sectional study in a hospital to observe the effect of prone position on neurological patients with SARS-CoV-2. A total of 52 neurological patients with SARS-CoV-2 participated in the survey. Most patients (76.92%) had cerebrovascular disease combined with SARS-CoV-2. After prone position, the oxygen saturation increased by 3.25% ± 3.02%. The number of patients with an oxygen saturation of 95% or more increased by 28.85%. Among the 3 types of neurological diseases, the oxygen saturation improvement values in patients with encephalitis or encephalopathy was the greatest, and cerebrovascular disease was the least. Oxygen saturation improvements did not differ among delivery modes. Prone position nursing can improve the effect of oxygen therapy on patients with neurological diseases combined with SARS-CoV-2 infection. Prone position nursing can slow the need for advanced equipment such as ventilators during the COVID-19 pandemic., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Corticosteroids are commonly used to treat COVID-19 patients with hypoxemia, and clinicians have adjusted the corticosteroid intensity on the basis of clinical needs. However, neither the optimal dose nor the duration of treatment has been recommended., Objective: To investigate whether cumulative doses of corticosteroids, measured as dexamethasone-equivalent doses over the first 14 days, impact outcomes in patients with COVID-19 pneumonia., Methods: We conducted a retrospective cohort study of COVID-19 pneumonia patients admitted between April 1st, 2020, and September 30th, 2021. The study focused on the type and dose of corticosteroid administered during the initial 14 days, clinical outcomes, and complications. The primary outcome was in-hospital mortality., Results: Among 271 patients, the mean cumulative dexamethasone-equivalent dose was 158 (119.9-197.25) mg in survivors and 185 (131.7-222.0) mg in nonsurvivors. Univariate analysis revealed that the cumulative dexamethasone-equivalent dose was a risk factor for in-hospital mortality. However, this association did not hold true in the multivariate analysis. After the cumulative dexamethasone-equivalent dose was categorized into quartiles, the moderate dosage (126.01-165.00 mg) in the second quartile was found to be associated with the lowest in-hospital mortality (16.2%). Higher cumulative dexamethasone-equivalent doses were associated with longer hospital and ICU stays and fewer ventilator-free days (p < 0.001). Doses exceeding 165 mg were associated with an increased risk of hospital-acquired infections (p < 0.001)., Conclusions: The cumulative dexamethasone-equivalent dose during the first 14 days is not associated with in-hospital mortality in hypoxemic COVID-19 patients. However, higher cumulative doses exceeding 165 mg are associated with an increased risk of in-hospital mortality and secondary hospital-acquired infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Teeratakulpisarn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Conflict of Interest: No conflict of interest was declared by the author.

Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Background: In the postacute phase of coronavirus disease-2019 (COVID-19), survivors may have persistent symptoms, lung function abnormalities, and sequelae lesions on thoracic computed tomography (CT). This new entity has been defined as post-COVID interstitial lung disease (ILD) or residual disease., Aims: To evaluate the characteristics, risk factors and clinical significance of post-COVID ILD., Study Design: Multicenter cross-sectional analysis of data from a randomized clinical study., Methods: In this study, patients with persistent respiratory symptoms 3 months after recovery from COVID-19 were evaluated by two pulmonologists and a radiologist. post-COVID ILD was defined as the presence of respiratory symptoms, hypoxemia, restrictive defect on lung function tests, and interstitial changes on follow-up high-resolution computed tomography (HRCT)., Results: At the three-month follow-up, 375 patients with post-COVID-19 syndrome were evaluated, and 262 patients were found to have post-COVID ILD. The most prevalent complaints were dyspnea (n = 238, 90.8%), exercise intolerance (n = 166, 63.4%), fatigue (n = 142, 54.2%), and cough (n = 136, 52%). The mean Medical Research Council dyspnea score was 2.1 ± 0.9, oxygen saturation was 92.2 ± 5.9%, and 6-minute walking distance was 360 ± 140 meters. The mean diffusing capacity of the lung for carbon monoxide was 58 ± 21, and the forced vital capacity was 70% ± 19%. Ground glass opacities and fibrotic bands were the most common findings on thoracic HRCT. Fibrosis-like lesions such as interlobular septal thickening and traction bronchiectasis were observed in 38.3% and 27.9% of the patients, respectively. No honeycomb cysts were observed. Active smoking [odds ratio (OR), 1.96; 95% confidence interval (CI), 1.44-2.67), intensive care unit admission during the acute phase (OR, 1.46; 95% CI, 1.1-1.95), need for high-flow nasal oxygen (OR, 1.55; 95% CI, 1.42-1.9) or non-invasive ventilation (OR, 1.31; 95% CI, 0.8-2.07), and elevated serum lactate dehydrogenase levels (OR, 1.23; 95% CI 1.18-1.28) were associated with the development of post-COVID ILD. At the 6-month follow-up, the respiratory symptoms and pulmonary functions had improved spontaneously without any specific treatment in 35 patients (13.4%). The radiological interstitial lesions had spontaneously regressed in 54 patients (20.6%)., Conclusion: The co-existence of respiratory symptoms, radiological parenchymal lesions, and pulmonary functional abnormalities which suggest a restrictive ventilatory defect should be defined as post-COVID-19 ILD. However, the term “fibrosis” should be used carefully. Active smoking, severe COVID-19, and elevated lactate dehydrogenase level are the main risk factors of this condition. These post-COVID functional and radiological changes could disappear over time in 20% of the patients., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest.

Angiotensin-converting enzyme 2 (ACE2) is considered a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor of high importance, but due to its non-ubiquitous expression, studies of other proteins that may participate in virus internalisation have been undertaken. To date, many alternative receptors have been discovered. Their functioning may provide an explanation for some of the events observed in severe COVID-19 that cannot be directly explained by the model in which ACE2 constitutes the central point of infection. Diabetes mellitus type 2 (T2D) can induce severe COVID-19 development. Although many mechanisms associated with ACE2 can lead to increased SARS-CoV-2 virulence in diabetes, proteins such as basigin (CD147), glucose-regulated protein 78 kDa (GRP78), cluster of differentiation 4 (CD4), transferrin receptor (TfR), integrins α 5 β 1 /α v β 3 , or ACE2 co-receptors neuropilin 2 (NRP2), vimentin, and even syalilated gangliosides may also be responsible for worsening the COVID-19 course. On the other hand, some others may play protective roles. Understanding how diabetes-associated mechanisms can induce severe COVID-19 via modification of virus receptor functioning needs further extensive studies.

Background: Transfusion-related acute lung injury (TRALI) is a rare life-threatening complication of blood product transfusion. Intravenous immunoglobulin (IVIG)-related TRALI is scarcely reported., Case Presentation: A 63-year-old male patient suffering from multiple sclerosis treated with half-yearly rituximab infusions, was hospitalized due to dry cough, daily fever and shivering for seven days despite antibiotic therapy. Because of the history of COVID-19 one month prior without the symptoms having improved since, persistent bilateral multifocal areas of ground glass opacities in chest computed tomography and positive SARS-CoV-2 PCR from bronchoalveolar lavage with a cycling time of 30.1 COVID-19 due to long-shedding SARS-CoV-2 under immunosuppression with rituximab was diagnosed. He received treatment with nirmatrelvir und ritonavir and because of diagnosed IgG deficiency additionally a single dose of 20 g IVIG. During the IVIG infusion, the patient acutely developed tachycardia, hypotension, fever, chills, and hypoxemic respiratory failure due to pulmonary edema. TRALI was promptly diagnosed, and the patient was transferred to the intensive care unit for non-invasive ventilation for less than 24 h. The patient was discharged home from regular ward 72 h later in a good general condition and no remaining symptoms of TRALI., Conclusion: IVIG-related TRALI is a rare but life-threating condition and prompt recognition is lifesaving. Due to an increased use of IVIG not only in long-shedding SARS-CoV-2, an increase of TRALI incidence is expected., (© 2024. The Author(s).)

Long COVID has been linked to a decline in physical activity and functional capacity. However, it remains unclear which physical symptoms are associated with specific aspects of movement behaviors and functional capacity. We aimed to investigate the associations of fatigue, dyspnea, post-exertional malaise, myalgia, and the co-occurrence of symptoms with movement behaviors and functional capacity in individuals with Long COVID. A cross-sectional multicenter study was conducted. Questionnaires were used to assess fatigue, dyspnea, post-exertional malaise, and myalgia. Accelerometry was employed to assess sedentary time, steps per day, light physical activity, and moderate-to-vigorous physical activity. The six-minute walk test, 30-s chair stand test, and timed up and go were used to assess functional capacity. One hundred and two community-dwelling individuals who had been living with Long COVID for 15 ± 10 months participated in the study. Fatigue, post-exertional malaise, and the co-occurrence of physical symptoms showed a negative association with step count, while post-exertional malaise was also negatively associated with moderate-to-vigorous physical activity. Dyspnea showed a negative association with the functional score, including all tests. Our findings suggest that fatigue, post-exertional malaise, and the co-occurrence of physical symptoms are negatively associated with physical activity, while dyspnea is negatively associated with functional capacity in individuals with Long COVID., (© 2024. The Author(s).)