Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients.

Background: Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters within an integrated fashion could predict the disease course would help to stratify LTCS patients from acute COVID-19 or recovered patients. This could even allow to elucidation of a potential mechanistic role of these biomolecules during the disease course. Methods: This study comprised subjects with acute COVID-19 (n=7; longitudinal), LTCS (n=33), Recov (n=12), and no history of positive testing (n=73). 1H-NMR-based metabolomics with IVDr standard operating procedures verified and phenotyped all blood samples by quantifying 38 metabolites and 112 lipoprotein properties. Univariate and multivariate statistics identified NMR-based and cytokine changes. Results: Here, we report on an integrated analysis of serum/plasma by NMR spectroscopy and flow cytometry-based cytokines/chemokines quantification in LTCS patients. We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls (HC) or acute COVID-19 patients. Subsequently, correlation analysis in LTCS group only among cytokines and amino acids revealed that histidine and glutamine were uniquely attributed mainly with pro-inflammatory cytokines. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared with HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their phenylalanine, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except for IL-18 chemokine, which tended to be higher in LTCS patients. Conclusion: The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients.

Portable nanopore-sequencing technology: Trends in development and applications.

Sequencing technology is the most commonly used technology in molecular biology research and an essential pillar for the development and applications of molecular biology. Since 1977, when the first generation of sequencing technology opened the door to interpreting the genetic code, sequencing technology has been developing for three generations. It has applications in all aspects of life and scientific research, such as disease diagnosis, drug target discovery, pathological research, species protection, and SARS-CoV-2 detection. However, the first- and second-generation sequencing technology relied on fluorescence detection systems and DNA polymerization enzyme systems, which increased the cost of sequencing technology and limited its scope of applications. The third-generation sequencing technology performs PCR-free and single-molecule sequencing, but it still depends on the fluorescence detection device. To break through these limitations, researchers have made arduous efforts to develop a new advanced portable sequencing technology represented by nanopore sequencing. Nanopore technology has the advantages of small size and convenient portability, independent of biochemical reagents, and direct reading using physical methods. This paper reviews the research and development process of nanopore sequencing technology (NST) from the laboratory to commercially viable tools; discusses the main types of nanopore sequencing technologies and their various applications in solving a wide range of real-world problems. In addition, the paper collates the analysis tools necessary for performing different processing tasks in nanopore sequencing. Finally, we highlight the challenges of NST and its future research and application directions.

Messenger RNA in lipid nanoparticles rescues HEK 293 cells from lipid-induced mitochondrial dysfunction as studied by real time pulse chase NMR, RTPC-NMR, spectroscopy.

Analytical tools to study cell physiology are critical for optimizing drug-host interactions. Real time pulse chase NMR spectroscopy, RTPC-NMR, was introduced to monitor the kinetics of metabolite production in HEK 293T cells treated with COVID-19 vaccine-like lipid nanoparticles, LNPs, with and without mRNA. Kinetic flux parameters were resolved for the incorporation of isotopic label into metabolites and clearance of labeled metabolites from the cells. Changes in the characteristic times for alanine production implicated mitochondrial dysfunction as a consequence of treating the cells with lipid nanoparticles, LNPs. Mitochondrial dysfunction was largely abated by inclusion of mRNA in the LNPs, the presence of which increased the size and uniformity of the LNPs. The methodology is applicable to all cultured cells.

Molecular and Physiological Aspects of SARS-CoV-2 Infection in Women and Pregnancy.

Whilst scientific knowledge about SARS-CoV-2 and COVID-19 is rapidly increasing, much of the effects on pregnant women is still unknown. To accommodate pregnancy, the human endometrium must undergo a physiological transformation called decidualization. These changes encompass the remodeling of endometrial immune cells leading to immunotolerance of the semi-allogenic conceptus as well as defense against pathogens. The angiotensin converting enzyme 2 (ACE2) plays an important regulatory role in the renin-angiotensin-system (RAS) and has been shown to be protective against comorbidities known to worsen COVID-19 outcomes. Furthermore, ACE2 is also crucial for decidualization and thus for early gestation. An astounding gender difference has been found in COVID-19 with male patients presenting with more severe cases and higher mortality rates. This could be attributed to differences in sex chromosomes, hormone levels and behavior patterns. Despite profound changes in the female body during pregnancy, expectant mothers do not face worse outcomes compared with non-pregnant women. Whereas mother-to-child transmission through respiratory droplets during labor or in the postnatal period is known, another question of in utero transmission remains unanswered. Evidence of placental SARS-CoV-2 infection and expression of viral entry receptors at the maternal-fetal interface suggests the possibility of in utero transmission. SARS-CoV-2 can cause further harm through placental damage, maternal systemic inflammation, and hindered access to health care during the pandemic. More research on the effects of COVID-19 during early pregnancy as well as vaccination and treatment options for gravid patients is urgently needed.

Real-world impact of vaccination on coronavirus disease 2019 (COVID-19) incidence in healthcare personnel at an academic medical center.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) vaccination effectiveness in healthcare personnel (HCP) has been established. However, questions remain regarding its performance in high-risk healthcare occupations and work locations. We describe the effect of a COVID-19 HCP vaccination campaign on SARS-CoV-2 infection by timing of vaccination, job type, and work location. METHODS: We conducted a retrospective review of COVID-19 vaccination acceptance, incidence of postvaccination COVID-19, hospitalization, and mortality among 16,156 faculty, students, and staff at a large academic medical center. Data were collected 8 weeks prior to the start of phase 1a vaccination of frontline employees and ended 11 weeks after campaign onset. RESULTS: The COVID-19 incidence rate among HCP at our institution decreased from 3.2% during the 8 weeks prior to the start of vaccinations to 0.38% by 4 weeks after campaign initiation. COVID-19 risk was reduced among individuals who received a single vaccination (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.40-0.68; P < .0001) and was further reduced with 2 doses of vaccine (HR, 0.17; 95% CI, 0.09-0.32; P < .0001). By 2 weeks after the second dose, the observed case positivity rate was 0.04%. Among phase 1a HCP, we observed a lower risk of COVID-19 among physicians and a trend toward higher risk for respiratory therapists independent of vaccination status. Rates of infection were similar in a subgroup of nurses when examined by work location. CONCLUSIONS: Our findings show the real-world effectiveness of COVID-19 vaccination in HCP. Despite these encouraging results, unvaccinated HCP remain at an elevated risk of infection, highlighting the need for targeted outreach to combat vaccine hesitancy.

Effects of progressive muscle relaxation training on negative emotions and sleep quality in COVID-19 patients: A clinical observational study.

This study investigates the effect of progressive muscle relaxation training on negative mood and sleep quality in Coronavirus Pneumonia (COVID-19) patients.COVID-19 is an emerging infectious disease, and there is still uncertainty about when the outbreak will be contained and the effectiveness of treatments. Considering that this disease is highly contagious, patients need to be treated in isolation. This may lead to psychological symptoms such as anxiety and depression, and even sleep problems.This study is a clinical observation study.Participants included 79 COVID-19 patients admitted to a designated hospital for COVID-19 patients in Wuhan from February to March, 2020. Patients were selected and assigned to the control group and the observation group according to their wishes, with 40 and 39 cases in each group, respectively. The control group received routine treatment and nursing, and the observation group received progressive muscle relaxation training, in addition to the routine treatment and nursing. We compared scores of the Pittsburgh Sleep Quality Index Scale (PSQI), the Generalized Anxiety Disorder (GAD-7), and the Patient Health Questionnaire (PHQ-9) before and after the intervention.There was no significant difference in PSQI, GAD-7, and PHQ-9 scores between the control group and the observation group before the intervention (P > .05). After the intervention, the difference in scores of PSQI, GAD-7, and PHQ-9 in the 2 groups were statistically significant (P < .05).Progressive muscle relaxation training can significantly reduce anxiety and depression and improve sleep quality in COVID-19 patients during isolation treatment.Progressive muscle relaxation training was shown to improve the treatment effect of patients and is worthy of clinical promotion.