Potential Application of Modified mRNA in Cardiac Regeneration.

Heart failure remains the leading cause of human death worldwide. After a heart attack, the formation of scar tissue due to the massive death of cardiomyocytes leads to heart failure and sudden death in most cases. In addition, the regenerative ability of the adult heart is limited after injury, partly due to cell-cycle arrest in cardiomyocytes. In the current post-COVID-19 era, urgently authorized modified mRNA (modRNA) vaccines have been widely used to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, modRNA-based protein replacement may act as an alternative strategy for improving heart disease. It is a safe, effective, transient, low-immunogenic, and integration-free strategy for in vivo protein expression, in addition to recombinant protein and stem-cell regenerative therapies. In this review, we provide a summary of various cardiac factors that have been utilized with the modRNA method to enhance cardiovascular regeneration, cardiomyocyte proliferation, fibrosis inhibition, and apoptosis inhibition. We further discuss other cardiac factors, modRNA delivery methods, and injection methods using the modRNA approach to explore their application potential in heart disease. Factors for promoting cardiomyocyte proliferation such as a cocktail of three genes comprising FoxM1, Id1, and Jnk3-shRNA (FIJs), gp130, and melatonin have potential to be applied in the modRNA approach. We also discuss the current challenges with respect to modRNA-based cardiac regenerative medicine that need to be overcome to apply this approach to heart disease. This review provides a short description for investigators interested in the development of alternative cardiac regenerative medicines using the modRNA platform.

Psychophysiological Adaptations to Exercise Training in COVID-19 Patients: A Systematic Review.

Introduction: Many COVID-19 patients display adverse symptoms, such as reduced physical ability, poor quality of life, and impaired pulmonary function. Therefore, this systematic review is aimed at evaluating the effectiveness of physical exercise on various psychophysiological indicators among COVID-19 patients who may be at any stage of their illness (i.e., critically ill, hospitalized, postdischarge, and recovering). Methods: A systematic search was conducted in PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar from 2019 to 2021. Twenty-seven studies, which assessed a total of 1525 patients, were included and analysed. Results: Overall, data revealed significant improvements in the following parameters: physical function, dyspnoea, pulmonary function, quality of life (QOL), lower limb endurance and strength, anxiety, depression, physical activity level, muscle strength, oxygen saturation, fatigue, C-reactive protein (CRP), interleukin 6 (IL-6), tumour necrosis factor-alpha (TNF-α), lymphocyte, leukocytes, and a fibrin degradation product (D-dimer). Conclusions: Physical training turns out to be an effective therapy that minimises the severity of COVID-19 in the intervention group compared to the standard treatment. Therefore, physical training could be incorporated into conventional treatment of COVID-19 patients. More randomized controlled studies with follow-up evaluations are required to evaluate the long-term advantages of physical training. Future research is essential to establish the optimal exercise intensity level and assess the musculoskeletal fitness of recovered COVID-19 patients. This trial is registered with CRD42021283087.

Intravenous immunoglobulins for the treatment of prolonged COVID-19 in immunocompromised patients: a brief report.

Primary humoral deficiency and secondary B-cell depletion may lead to prolonged Sars-Cov-2 infection due to a decreased viral clearance. Prolonged infection is mainly driven by the lack of anti-Sars-Cov-2 immunoglobulin (IVIg) especially in patients with no vaccine response. Anti-spike immunoglobulin can be provided by infusion of convalescent patients' plasma: recent studies highlighted that commercial immunoglobulin show high titers of neutralizing IgG. We conducted a single center retrospective cohort. We included 9 patients (6 males, median age 74 years old): one patient with X-linked agammaglobulinemia and 8 patients treated with rituximab (2 granulomatosis with polyangiitis, 1 neuromyelitis optica, 4 low grade B-cell lymphoma and 1 EBV post-transplant lymphoproliferative disorder). Mean serum globulin was 4 ± 1.6 g/L. 7/8 had received at least 3 doses of mRNA anti-Sars-Cov-2 vaccine (median 4) with no response (anti-Spike IgG 0 for 6 patients). In this specific population requiring oxygen therapy but no intensive care support, the administration of IVIg was well tolerated and provided a swift improvement of clinical status, a significant decrease of inflammation associated to the an improvement of radiological patterns. Our results suggest that immunoglobulin could be used as a salvage therapy as an alternative to convalescent plasma but highly stringent patient selection is required due to the worldwide shortage of IVIg.

The association between enteral nutrition with survival of critical patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) results in several complications and mortality in intensive care unit (ICU) patients. Limited studies have investigated the effect of enteral nutrition (EN) on the survival of COVID-19 patients in the ICU. The aim of this study was to investigate the association of EN with biochemical and pathological indices associated with mortality in ICU patients with COVID-19. METHODS: This case-control study was conducted on 240 patients with COVID-19 hospitalized in the ICU including 120 eventual nonsurvived as the cases and 120 survived patients as the controls. All of the patients received EN as a high protein high volume or standard formula. Data on general information, anthropometric measurements, and the results of lab tests were collected. RESULTS: The recovered patients received significantly more high protein (60.8% vs. 39.6%, p = .004) and high volume (61.6% vs. 42.3%, p = .005) formula compared to the nonsurvived group. Mortality was inversely associated with high volume (odds ratio [OR]: 0.45 confidence interval [CI]95%, p = .008) and high protein (OR: 0.42 CI95%, p = .003) formula. The results remained significant after adjusting for age and sex. Further adjustment for underlying diseases, smoking, body mass index, and the acute physiology and chronic health evaluation II (APACHE II) score did not change the results. CONCLUSION: The findings of the study showed that there was a significant inverse association between mortality and high volume and high protein formula in patients with COVID-19. Further investigation is warranted.

The Main Mechanisms of Mesenchymal Stem Cell-Based Treatments against COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a clinical manifestation of hypoxic respiratory failure and acute respiratory distress syndrome. However, COVID-19 still lacks of effective clinical treatments so far. As a promising potential treatment against COVID-19, stem cell therapy raised recently and had attracted much attention. Here we review the mechanisms of mesenchymal stem cell-based treatments against COVID-19, and provide potential cues for the effective control of COVID-19 in the future. METHODS: Literature is obtained from databases PubMed and Web of Science. Key words were chosen for COVID- 19, acute respiratory syndrome coronavirus 2, mesenchymal stem cells, stem cell therapy, and therapeutic mechanism. Then we summarize and critically analyze the relevant articles retrieved. RESULTS: Mesenchymal stem cell therapy is a potential effective treatment against COVID-19. Its therapeutic efficacy is mainly reflected in reducing severe pulmonary inflammation, reducing lung injury, improving pulmonary function, protecting and repairing lung tissue of the patients. Possible therapeutic mechanisms might include immunoregulation, anti-inflammatory effect, tissue regeneration, anti-apoptosis effect, antiviral, and antibacterial effect, MSC - EVs, and so on. CONCLUSION: Mesenchymal stem cells can effectively treat COVID-19 through immunoregulation, anti-inflammatory, tissue regeneration, anti-apoptosis, anti-virus and antibacterial, MSC - EVs, and other ways. Systematically elucidating the mechanisms of mesenchymal stem cell-based treatments for COVID-19 will provide novel insights into the follow-up research and development of new therapeutic strategies in next step.

Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis.

While the COVID-19 outbreak and its complications are still under investigation, post-inflammatory pulmonary fibrosis (PF) has already been described as a long-term sequela of acute respiratory distress syndrome (ARDS) secondary to SARS-CoV2 infection. However, therapeutical strategies for patients with ARDS and PF are still limited and do not significantly extend lifespan. So far, lung transplantation remains the only definitive treatment for end-stage PF. Over the last years, numerous preclinical and clinical studies have shown that allogeneic mesenchymal stromal cells (MSCs) might represent a promising therapeutical approach in several lung disorders, and their potential for ARDS treatment and PF prevention has been investigated during the COVID-19 pandemic. From April 2020 to April 2022, we treated six adult patients with moderate COVID-19-related ARDS in a late proliferative stage with up to two same-dose infusions of third-party allogeneic bone marrow-derived MSCs (BM-MSCs), administered intravenously 15 days apart. No major adverse events were registered. Four patients completed the treatment and reached ICU discharge, while two received only one dose of MSCs due to multiorgan dysfunction syndrome (MODS) and subsequent death. All four survivors showed improved gas exchanges (PaO2/FiO2 ratio > 200), contrary to the others. Furthermore, LDH trends after MSCs significantly differed between survivors and the deceased. Although further investigations and shared protocols are still needed, the safety of MSC therapy has been recurrently shown, and its potential in treating ARDS and preventing PF might represent a new therapeutic strategy.

Treatment of COVID-19-associated ARDS with umbilical cord-derived mesenchymal stromal cells in the STROMA-CoV-2 multicenter randomized double-blind trial: long-term safety, respiratory function, and quality of life.

BACKGROUND: The STROMA-CoV-2 study was a French phase 2b, multicenter, double-blind, randomized, placebo-controlled clinical trial that did not identify a significant efficacy of umbilical cord-derived mesenchymal stromal cells in patients with SARS-CoV-2-induced acute respiratory distress syndrome. Safety on day 28 was found to be good. The aim of our extended study was to assess the 6- and 12-month safety of UC-MSCs administration in the STROMA-CoV-2 cohort. METHODS: A detailed multi-domain assessment was conducted at 6 and 12 months following hospital discharge focusing on adverse events, lung computed tomography-scan, pulmonary and muscular functional status, and quality of life in the STROMA-CoV-2 cohort including SARS-CoV-2-related early (< 96 h) mild-to-severe acute respiratory distress syndrome. RESULTS: Between April 2020 and October 2020, 47 patients were enrolled, of whom 19 completed a 1-year follow-up. There were no significant differences in any endpoints or adverse effects between the UC-MSCs and placebo groups at the 6- and 12-month assessments. Ground-glass opacities persisted at 1 year in 5 patients (26.3%). Furthermore, diffusing capacity for carbon monoxide remained altered over 1 year, although no patient required oxygen or non-invasive ventilatory support. Quality of life revealed declines in mental, emotional and physical health throughout the follow-up period, and the six-minute walking distance remained slightly impaired at the 1-year patient assessment. CONCLUSIONS: This study suggests a favorable safety profile for the use of intravenous UC-MSCs in the context of the first French wave of SARS-CoV-2-related moderate-to-severe acute respiratory distress syndrome, with no adverse effects observed at 1 year.

COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

Convalescent plasma transfusion for immunocompromised viremic patients with COVID-19: A retrospective multicenter study.

This study aims to assess the safety, virological, and clinical outcomes of convalescent plasma transfusion (CPT) in immunocompromised patients hospitalized for coronavirus disease 2019 (COVID-19). We conducted a retrospective multicenter cohort study that included all immunosuppressed patients with COVID-19 and RNAemia from May 2020 to March 2023 treated with CPT. We included 81 patients with hematological malignancies (HM), transplants, or autoimmune diseases (69% treated with anti-CD20). Sixty patients (74%) were vaccinated, and 14 had pre-CPT serology >264 BAU/mL. The median delay between symptom onset and CPT was 23 days [13-31]. At D7 post-CPT, plasma PCR was negative in 43/64 patients (67.2%), and serology became positive in 25/30 patients (82%). Post-CPT positive serology was associated with RNAemia negativity (p < 0.001). The overall mortality rate at D28 was 26%, being higher in patients with non-B-cell HM (62%) than with B-cell HM (25%) or with no HM (11%) (p = 0.02). Patients receiving anti-CD20 without chemotherapy had the lowest mortality rate (8%). Positive RNAemia at D7 was associated with mortality at D28 in univariate analysis (HR: 3.05 [1.14-8.19]). Eight patients had adverse events, two of which were severe but transient. Our findings suggest that CPT can abolish RNAemia and ameliorate the clinical course in immunocompromised patients with COVID-19.

Two- and 3-year outcomes in convalescent individuals with COVID-19: A prospective cohort study.

As the long-term consequences of coronavirus disease 2019 (COVID-19) have not been defined, it is necessary to explore persistent symptoms, long-term respiratory impairment, and impact on quality of life over time in COVID-19 survivors. In this prospective cohort study, convalescent individuals diagnosed with COVID-19 were followed-up 2 and 3 years after discharge from hospital. Participants completed an in-person interview to assess persistent symptoms and underwent blood tests, pulmonary function tests, chest high-resolution computed tomography, and the 6-min walking test. There were 762 patients at the 2-year follow-up and 613 patients at the 3-year follow-up. The mean age was 60 years and 415 (54.5%) were men. At 3 years, 39.80% of the participants had at least one symptom; most frequently, fatigue, difficulty sleeping, joint pain, shortness of breath, muscle aches, and cough. The participants experienced different degrees of pulmonary function impairment, with decreased carbon monoxide diffusion capacity being the main feature; results remained relatively stable over the 2-3 years. Multiple logistic regression analysis demonstrated that female sex and smoking were independently associated with impaired diffusion capacity. A subgroup analysis based on disease severity was performed, indicating that there was no difference in other parameters of lung function except forced vital capacity at 3-year follow-up. Persistent radiographic abnormalities, most commonly fibrotic-like changes, were observed at both timepoints. At 3 years, patients had a significantly improved Mental Component Score compared with that at 2 years, with a lower percentage with anxiety. Our study indicated that symptoms and pulmonary abnormalities persisted in COVID-19 survivors at 3 years. Further studies are warranted to explore the long-term effects of COVID-19 and develop appropriate rehabilitation strategies.

Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study.

Respiratory viral infections (RVIs) are common reasons for healthcare consultations. The inpatient management of RVIs consumes significant resources. From 2009 to 2014, we assessed the costs of RVI management in 4776 hospitalized children aged 0-18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by detailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU ('non-ICU') versus management requiring ICU care ('ICU') added up to EUR 2767.14 (non-ICU) vs. EUR 29,941.71 (ICU) for influenza, EUR 2713.14 (non-ICU) vs. EUR 16,951.06 (ICU) for RSV infections, and EUR 2767.33 (non-ICU) vs. EUR 14,394.02 (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all eight RVIs studied: influenza, RSV, hRV, adenovirus (hAdV), metapneumovirus (hMPV), parainfluenza virus (hPIV), bocavirus (hBoV), and seasonal coronavirus (hCoV) infections. ICU costs for influenza, however, exceeded all other RVIs. At the time of the study, influenza was the only RVI with antiviral treatment options available for children, but only 9.8% of influenza patients (non-ICU) and 1.5% of ICU patients with influenza received antivirals; only 2.9% were vaccinated. Future studies should investigate the economic impact of treatment and prevention of influenza, COVID-19, and RSV post vaccine introduction.

Challenges for palliative care in times of COVID-19: a scoping review.

Introduction: Many of the essential practices in palliative care (PC) had to be adapted to the COVID-19 pandemic. This global spread of the infectious respiratory disease, caused by SARS-CoV-2, created unprecedented obstacles. The aim of this research was to comprehensively assess the experiences and perceptions of healthcare professionals, individuals, and families in palliative and end-of-life situations during the COVID-19 pandemic. Methods: A scoping review was conducted using the databases CINAHL Complete, MEDLINE, Scopus, SciELO, Cochrane Central Register of Controlled Trials, Psychology and Behavioral Sciences, MEDIClatina, and Portugal's Open Access Scientific Repository. The review followed the JBI® methodological approach for scoping reviews. Results: Out of the initially identified 999 articles, 22 studies were included for analysis. The deprivation of relationships due to the safety protocols required to control the spread of COVID-19 was a universally perceived experience by healthcare professionals, individuals in PC, and their families. Social isolation, with significant psychological impact, including depersonalization and despair, was among the most frequently reported experiences by individuals in palliative situation. Despite healthcare professionals' efforts to mitigate the lack of relationships, the families of these individuals emphasized the irreplaceability of in-person bedside contact. Systematic review registration: https://osf.io/xmpf2/.

Multisystem inflammatory syndrome in children: an Umbrella review.

We conducted an Umbrella review of eligible studies to evaluate what patient features have been investigated in the multisystem inflammatory syndrome in children (MIS-C) population, in order to guide future investigations. We comprehensively searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from December 1, 2019 to the May 6, 2022. The time period was limited to cover the coronavirus disease-2019 (COVID-19) pandemic period. The protocol was registered in the PROSPERO registry (CRD42022340228). Eligible studies included (1) a study population of pediatric patients ≤21 years of age diagnosed with MIS-C; (2) an original Systematic review or Mata-analysis; (3) published 2020 afterward; and (4) was published in English. A total of 41 studies met inclusion criteria and underwent qualitative analysis. 28 studies reported outcome data of MIS-C. 22 studies selected clinical features of MIS-C, and 6 studies chose demographic data as a main topic. The mortality rate for children with MIS-C was 1.9% (interquartile range (IQR) 0.48), the ICU admission rate was 72.6% (IQR 8.3), and the extracorporeal membrane oxygenation rate was 4.7% (IQR 2.0). A meta-analysis of eligible studies found that cerebral natriuretic peptide in children with MIS-C was higher than that in children with COVID-19, and that the use of intravenous immunoglobulin (IVIG) in combination with glucocorticoids to treat MIS-C compared to IVIG alone was associated with lower treatment failure. In the future, for patients with MIS-C, studies focused on safety of surgery requiring general anesthesia, risk factors, treatment, and long-term outcomes are warranted.

Association between a low-risk COVID-19 extracorporeal membrane oxygenation criteria and mortality: A retrospective study.

OBJECTIVE: Our study aimed to compare the outcomes of COVID-19 patients who met a low-risk inclusion criteria for veno-venous extra corporeal membrane oxygenation (VV ECMO) with those who did not meet criteria due to higher risk but were subsequently cannulated. METHODS: This was a retrospective observational cohort study that included adult patients who were placed on VV ECMO for COVID-19 related acute respiratory distress syndrome (ARDS) at a tertiary care academic medical center. The primary outcome was the association between the low-risk criteria and mortality. The patients met the criteria if they met EOLIA severe ARDS criteria, no absolute contraindications (age > 60 years, BMI > 55 kg/m2, mechanical ventilation (MV) duration >7 days, irreversible neurologic damage, chronic lung disease, active malignancy, or advanced multiorgan dysfunction), and had three or less relative contraindications (age > 50 years, BMI > 45 kg/m2, comorbidities, MV duration > 4 days, acute kidney injury, receiving vasopressors, hospital LOS > 14 days, or COVID-19 diagnosis > 4 weeks). RESULTS: Sixty-five patients were included from March 2020 through March 2022. Patients were stratified into low-risk or high-risk categories. The median Sequential Organ Failure Assessment score was 7 and the median PaO2/FiO2 ratio was 44 at the time of ECMO cannulation. The in-hospital mortality was 47.8% in the low-risk group and 69.0% in the high-risk group (p = 0.096). CONCLUSION: There was not a statistically significant difference in survival between low-risk patients and high-risk patients; however, there was a trend toward higher survival in the lower-risk group.

Plasma neutrophil gelatinase-associated lipocalin independently predicts dialysis need and mortality in critical COVID-19.

Neutrophil gelatinase-associated lipocalin (NGAL) is a novel kidney injury and inflammation biomarker. We investigated whether NGAL could be used to predict continuous renal replacement therapy (CRRT) and mortality in critical coronavirus disease 2019 (COVID-19). This prospective multicenter cohort study included adult COVID-19 patients in six intensive care units (ICUs) in Sweden between May 11, 2020 and May 10, 2021. Blood was sampled at admission, days two and seven in the ICU. The samples were batch analyzed for NGAL, creatinine, and cystatin c after the end of the study period. Initiation of CRRT and 90-day survival were used as dependent variables in regression models. Of 498 included patients, 494 were analyzed regarding CRRT and 399 were analyzed regarding survival. Seventy patients received CRRT and 154 patients did not survive past 90 days. NGAL, in combination with creatinine and cystatin c, predicted the subsequent initiation of CRRT with an area under the curve (AUC) of 0.95. For mortality, NGAL, in combination with age and sex, had an AUC of 0.83. In conclusion, NGAL is a valuable biomarker for predicting subsequent initiation of CRRT and 90-day mortality in critical COVID-19. NGAL should be considered when developing future clinical scoring systems.

IA-PACS-CFS: a double-blinded, randomized, sham-controlled, exploratory trial of immunoadsorption in patients with chronic fatigue syndrome (CFS) including patients with post-acute COVID-19 CFS (PACS-CFS).

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severely debilitating condition which markedly restricts activity and function of affected people. Since the beginning of the COVID-19 pandemic ME/CFS related to post-acute COVID-19 syndrome (PACS) can be diagnosed in a subset of patients presenting with persistent fatigue 6 months after a mostly mild SARS-CoV-2 infection by fulfillment of the Canadian Consensus Criteria (CCC 2003). Induction of autoimmunity after viral infection is a mechanism under intensive investigation. In patients with ME/CFS, autoantibodies against thyreoperoxidase (TPO), beta-adrenergic receptors (ß2AR), and muscarinic acetylcholine receptors (MAR) are frequently found, and there is evidence for effectiveness of immunomodulation with B cell depleting therapy, cyclophosphamide, or intravenous immunoglobulins (IVIG). Preliminary studies on the treatment of ME/CFS patients with immunoadsorption (IA), an apheresis that removes antibodies from plasma, suggest clinical improvement. However, evidence from placebo-controlled trials is currently missing. METHODS: In this double-blinded, randomized, sham-controlled, exploratory trial the therapeutic effect of five cycles of IA every other day in patients with ME/CFS, including patients with post-acute COVID-19 chronic fatigue syndrome (PACS-CFS), will be evaluated using the validated Chalder Fatigue Scale, a patient-reported outcome measurement. A total of 66 patients will be randomized at a 2:1 ratio: 44 patients will receive IA (active treatment group) and 22 patients will receive a sham apheresis (control group). Moreover, safety, tolerability, and the effect of IA on patient-reported outcome parameters, biomarker-related objectives, cognitive outcome measurements, and physical parameters will be assessed. Patients will be hospitalized at the clinical site from day 1 to day 10 to receive five IA treatments and medical visits. Four follow-up visits (including two visits at site and two visits via telephone call) at month 1 (day 30), 2 (day 60), 4 (day 120), and 6 (day 180; EOS, end of study visit) will take place. DISCUSSION: Although ME/CFS including PACS-CFS causes an immense individual, social, and economic burden, we lack efficient therapeutic options. The present study aims to investigate the efficacy of immunoadsorption and to contribute to the etiological understanding and establishment of diagnostic tools for ME/CFS. TRIAL REGISTRATION: Registration Number: NCT05710770 . Registered on 02 February 2023.

Convalescent Plasma Therapy in Immunocompromised Patients Infected With the BA.1 or BA.2 Omicron SARS-CoV-2.

The emergence of SARS-CoV-2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with all monoclonal antibodies having lost any neutralization activity. We report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited from COVID-19 convalescent plasma (CCP). At Day 28, the overall survival was 76% (95% CI 67-86) with no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or autoimmune diseases. No safety concern was reported during the course of the study. These results showed that CCP is well tolerated and represents a treatment option for immunocompromised patients who remain highly impacted by the COVID19 epidemic.

Baseline immune status and the effectiveness of response to enteral nutrition among ICU patients with COVID-19: An observational, retrospective study.

OBJECTIVES: This study aimed to compare how immunocompromised and immunocompetent patients responded differently to enteral nutrition (EN) support in intensive care units (ICUs) during the COVID-19 pandemic, including serum nutritional biomarkers, inflammatory biomarkers, gastrointestinal (GI) intolerance symptoms, and clinical outcomes. METHODS: An observational, retrospective study was conducted in the ICUs of a teaching hospital in southwest China. We recruited a convenience sample of 154 patients between December 2022 and February 2023. We defined immunocompromise as primary immunodeficiency diseases, active malignancy, receiving cancer chemotherapy, HIV infection, solid organ transplantation, hematopoietic stem cell transplantation, receiving corticosteroid therapy with a target dose, receiving biological immune modulators, or receiving disease-modifying antirheumatic drugs or other immunosuppressive drugs. We conducted a Mann-Whitney U test, χ2 test, or generalized estimation equation model to explore the differences between immunocompromised and immunocompetent patients. RESULTS: Among the 154 study participants, 41 (27%) were defined as immunocompromised. The immunocompromised patients were younger than the immunocompetent patients. There were no statistically significant differences between the two groups with respect to serum nutritional biomarkers, inflammatory biomarkers, incidence of GI intolerance symptoms, and in-hospital mortality. However, the immunocompromised patients exhibited a longer hospitalization duration than the immunocompetent patients. CONCLUSION: We found that the immunocompromised patients spent more time in the hospital. These findings may help us to standardize the participants before EN interventional studies better and better individualize EN supports based on patients' immunity status.

Advances in lipid nanoparticle mRNA therapeutics beyond COVID-19 vaccines.

The remarkable success of two lipid nanoparticle-mRNA vaccines against coronavirus disease (COVID-19) has placed the therapeutic and prophylactic potential of messenger RNA (mRNA) in the spotlight. It has also drawn attention to the indispensable role of lipid nanoparticles in enabling the effects of this nucleic acid. To date, lipid nanoparticles are the most clinically advanced non-viral platforms for mRNA delivery. This is thanks to their favorable safety profile and efficiency in protecting the nucleic acid from degradation and allowing its cellular uptake and cytoplasmic release upon endosomal escape. Moreover, the development of lipid nanoparticle-mRNA therapeutics was already a very active area of research even before the COVID-19 pandemic, which has likely only begun to bear its fruits. In this Review, we first discuss key aspects of the development of lipid nanoparticles as mRNA carriers. We then highlight promising preclinical and clinical studies involving lipid nanoparticle-mRNA formulations against infectious diseases and cancer, and to enable protein replacement or supplementation and genome editing. Finally, we elaborate on the challenges in advancing lipid nanoparticle-mRNA technology to widespread therapeutic use.