Background: While some long-term effects of COVID-19 are respiratory in nature, a non-respiratory effect gaining attention has been a decline in hemoglobin, potentially mediated by inflammatory processes. In this study, we examined the correlations between hemoglobin levels and inflammatory biomarkers and evaluated the association between hemoglobin and fatigue in a cohort of Long-COVID patients. Methods: This prospective cohort study in the Netherlands evaluated 95 (mostly hospitalized) patients, aged 40-65 years, 3-6 months post SARS-CoV-2 infection, examining their venous hemoglobin concentration, anemia (hemoglobin < 7.5 mmol/L in women and <8.5 mmol/L in men), inflammatory blood biomarkers, average FSS (Fatigue Severity Score), demographics, and clinical features. Follow-up hemoglobin was compared against hemoglobin during acute infection. Spearman correlation was used for assessing the relationship between hemoglobin concentrations and inflammatory biomarkers, and the association between hemoglobin and fatigue was examined using logistic regression. Results: In total, 11 (16.4%) participants were suffering from anemia 3-6 months after SARS-CoV-2 infection. The mean hemoglobin value increased by 0.3 mmol/L 3-6 months after infection compared to the hemoglobin during the acute phase (p-value = 0.003). Whilst logistic regression showed that a 1 mmol/L greater increase in hemoglobin is related to a decrease in experiencing fatigue in Long-COVID patients (adjusted OR 0.38 [95%CI 0.13-1.09]), we observed no correlations between hemoglobin and any of the inflammatory biomarkers examined. Conclusion: Our results indicate that hemoglobin impairment might play a role in developing Long-COVID fatigue. Further investigation is necessary to identify the precise mechanism causing hemoglobin alteration in these patients.

In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

To evaluate current evidence on the utility of hydrocortisone, ascorbic acid and thiamine (HAT) therapy for the management of septic shock.

The following keyword search terms were utilized in PubMed to identify relevant articles: ascorbic acid, thiamine, hydrocortisone, shock, and critical care. Articles relevant to HAT therapy in patients with septic shock were selected. Retrospective cohorts and randomized controlled trials were included in this review; case reports/series were excluded. Data from included studies illustrating the use of HAT therapy for the management of sepsis and septic shock, including data on time to HAT therapy initiation, severity of illness at baseline, duration of vasopressor therapy, progression of organ failure, and mortality, were evaluated.

The utilization of HAT therapy for the management of sepsis and septic shock remains controversial. Hemodynamic benefits have been shown to be most pronounced when HAT therapy is initiated earlier. Future studies directed at earlier initiation may be necessary to confirm this theory.

Vitamins are essential micronutrients with key roles in many biological pathways relevant to sepsis. Some of these relevant biological mechanisms include antioxidant and anti-inflammatory effects, protein and hormone synthesis, energy generation, and regulation of gene transcription. Moreover, relative vitamin deficiencies in plasma are common during sepsis and vitamin therapy has been associated with improved outcomes in some adult and pediatric studies. High-dose intravenous vitamin C has been the vitamin therapy most extensively studied in adult patients with sepsis and septic shock. This includes three randomized control trials (RCTs) as monotherapy with a total of 219 patients showing significant reduction in organ dysfunction and lower mortality when compared to placebo, and five RCTs as a combination therapy with thiamine and hydrocortisone with a total of 1134 patients showing no difference in clinical outcomes. Likewise, the evidence for the role of other vitamins in sepsis remains mixed. In this narrative review, we present the preclinical, clinical, and safety evidence of the most studied vitamins in sepsis, including vitamin C, thiamine (i.e., vitamin B₁), and vitamin D. We also present the relevant evidence of the other vitamins that have been studied in sepsis and critical illness in both children and adults, including vitamins A, B₂, B₆, B₁₂, and E. IMPACT: Vitamins are key effectors in many biological processes relevant to sepsis. We present the preclinical, clinical, and safety evidence of the most studied vitamins in pediatric sepsis. Designing response-adaptive platform trials may help fill in knowledge gaps regarding vitamin use for critical illness and association with clinical outcomes.

Plant biostimulants are under investigation as innovative products to improve plant production and fruit quality, without resulting in environmental and food contaminations. Here, the effects of the application of Expando, a biostimulant based on seaweed and yeast extracts, on plant productivity, fruit ripening times, and fruit quality of Solanum lycopersicum var. Micro-Tom were evaluated. After biostimulant treatment, a two-week reduction of ripening times and a concomitant enhancement of the production percentage during the earliest ripening times, in terms of both fruit yield (+110%) and size (+85%), were observed. Concerning fruit quality, proximate analysis showed that tomatoes treated with the biostimulant had better nutritional composition compared to untreated samples, since both the quality of unsatured fatty acids (C16:3ω3: +328%; C18:2ω6: -23%) and micronutrients essential for human health (Fe: +14%; Cu: +21%; Zn: +24%) were increased. From a nutraceutical point of view, despite strong changes in bioactive compound profile not being observed, an increase of the antioxidant properties was recorded in fruits harvested by plants treated with the biostimulant (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS): +38%; 2,2-diphenyl-1-picrylhydrazyl (DPPH): +11%). In conclusion, the biostimulant application was able to reduce the ripening times and fruit size, while slightly increasing nutritional and nutraceutical values, leading to more marketable tomato fruits.

Oxidative stress plays an important role in cellular processes. Consequently, oxidative stress also affects etiology, progression, and response to therapeutics in various pathological conditions including malignant tumors. Oxidative stress and associated outcomes are often brought about by excessive generation of reactive oxygen species (ROS). Accumulation of ROS occurs due to dysregulation of homeostasis in an otherwise strictly controlled physiological condition. In fact, intracellular ROS levels are closely associated with the pathological status and outcome of numerous diseases. Notably, mitochondria are recognized as the critical regulator and primary source of ROS. Damage to mitochondria increases mitochondrial ROS (mROS) production, which leads to an increased level of total intracellular ROS. However, intracellular ROS level may not always reflect mROS levels, as ROS is not only produced by mitochondria but also by other organelles such as endoplasmic reticulum and peroxisomes. Thus, an evaluation of mROS would help us to recognize the biological and pathological characteristics and predictive markers of malignant tumors and develop efficient treatment strategies. In this review, we describe the pathological significance of mROS in malignant neoplasms. In particular, we show the association of mROS-related signaling in the molecular mechanisms of chemically synthesized and natural chemotherapeutic agents and photodynamic therapy.