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The Influence of Obesity and Weight Loss on the Bioregulation of Innate/Inflammatory Responses: Macrophages and Immunometabolism.
Gálvez, I, Navarro, MC, Martín-Cordero, L, Otero, E, Hinchado, MD, Ortega, E
Nutrients. 2022;(3)
Abstract
Obesity is characterized by low-grade inflammation and more susceptibility to infection, particularly viral infections, as clearly demonstrated in COVID-19. In this context, immunometabolism and metabolic flexibility of macrophages play an important role. Since inflammation is an inherent part of the innate response, strategies for decreasing the inflammatory response must avoid immunocompromise the innate defenses against pathogen challenges. The concept "bioregulation of inflammatory/innate responses" was coined in the context of the effects of exercise on these responses, implying a reduction in excessive inflammatory response, together with the preservation or stimulation of the innate response, with good transitions between pro- and anti-inflammatory macrophages adapted to each individual's inflammatory set-point in inflammatory diseases, particularly in obesity. The question now is whether these responses can be obtained in the context of weight loss by dietary interventions (low-fat diet or abandonment of the high-fat diet) in the absence of exercise, which can be especially relevant for obese individuals with difficulties exercising such as those suffering from persistent COVID-19. Results from recent studies are controversial and do not point to a clear anti-inflammatory effect of these dietary interventions, particularly in the adipose tissue. Further research focusing on the innate response is also necessary.
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COVID-19 in perinatal period: questions and consequences.
Tunçel, D, Bilgin, LK, İnce, Z, Çoban, A
The Turkish journal of pediatrics. 2022;(1):1-9
Abstract
BACKGROUND The effect of COVID-19 infection on newborn babies is not yet clear. Babies born to pregnant women with suspected or proven COVID-19 or babies who had contact with infected people are considered to be at risk. In this review, intrauterine problems that may be caused by COVID-19 infection, delivery room approach, postnatal follow-up, precautions and controversies regarding breastfeeding and vaccination are discussed. METHODS The articles published between March 2020 and June 2021 were searched in Pubmed, Cochrane Library and Google Scholar databases using the keywords COVID-19 and newborn, perinatal period, vertical transmission, pregnancy, breast milk and vaccines. The updated information and recommendations are presented. CONCLUSIONS Our knowledge of the perinatal and neonatal effects of COVID-19 infection changes rapidly. Therefore, close follow-up of the mother-infant dyads is important. Larger epidemiological and clinical cohort studies are needed to better understand the possible implications and long-term outcomes of COVID-19 infection and also maternal vaccination in newborn infants.
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Investigation of obesity, eating behaviors and physical activity levels living in rural and urban areas during the covid-19 pandemic era: a study of Turkish adolescent.
Gülü, M, Yapici, H, Mainer-Pardos, E, Alves, AR, Nobari, H
BMC pediatrics. 2022;(1):405
Abstract
BACKGROUND The purpose of this study was to determine the eating behaviors, obesity and physical activity status of children of similar ages living in rural and urban areas and to examine these relationships during the coronavirus disease (COVID-19) pandemic process. METHOD The research was conducted using the scanning model. The research group consists of children living in rural and urban areas in Turkey. The sample of the study consists of a total of 733 adolescent participants, 351 females (47.9%) and 382 males (52.1%). After anthropometric measurements were made, the Physical Activity Questionnaire for older children and the Yale Food Addiction Scale for children 2.0 were used to determine the food addiction and physical activity status of children during the COVID19 pandemic process. Since the groups were homogeneously distributed, independent samples t-test and Pearson correlation test were used. RESULT In terms of food addiction and physical activity levels, children living in the urban have higher scores than children living in rural areas. In addition, children living in the urban were taller and have higher body mass values than those in rural areas. In terms of physical activity level and food addiction levels, while girls living in the urban had higher activity levels than those living in rural areas, no statistically significant difference was found between the physical activity levels of boys. When evaluated in terms of general and gender, it was determined that children living in rural areas were overweight and obese at a higher rate. Obese children had higher levels of food addiction and lower physical activity levels than non-obese children. CONCLUSION In order to prevent childhood obesity, the level of food addiction should be reduced as well as increasing the level of physical activity. This study is limited in terms of cross-sectional evaluation. Future research can experimentally reveal how much obesity is reduced by methods such as exercise and diet interventions.
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Impact of COVID-19 on the Destiny of Bariatric Patients.
Gualtieri, P, Marchetti, M, Renzo, LD, De Santis, GL, Palma, R, Colica, C, Frank, G, De Lorenzo, A, Di Lorenzo, N
Nutrients. 2022;(1)
Abstract
Obese patients reported worse outcomes of COVID-19 related to prothrombotic and low-grade inflammation status. During the SARS-CoV-2 outbreak, all non-elective surgeries were postponed, including bariatric surgery (BS). This umbrella review wants to underline obesity as a condition provoking low-grade chronic inflammation, and increasing severe COVID-19 risk; to relaunch the prioritization of BS. The literature search was conducted in March 2022 via Pubmed (MEDLINE) and focused on reviews, systematic reviews, and meta-analyses published in peer-reviewed journals. Terms "bariatric surgery" OR "obesity surgery" OR "metabolic surgery" were analyzed with "COVID-19" OR "SARS-CoV-2" using the AND modifier. Only 13 studies of the 406 screened met the objective. The procrastination of BS over the past two years determined a delay in obesity treatment and severe consequences. The COVID-19 pandemic has had a huge impact on economic costs. Although BS has high costs, a lifetime cost advantage over conventional weight loss methods was demonstrated. As the pandemic continues, health policies must recognize obesity as a disease-predisposing factor for SARS-CoV-2 infection, considering COVID-19 as a new comorbidity mitigable by BS. Care pathways for obese patients in COVID/post-COVID era should be revitalized and the concept of elective surgery attributed to BS should be reformulated.
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A state-of-the-art review on fucoidan as an antiviral agent to combat viral infections.
Pradhan, B, Nayak, R, Patra, S, Bhuyan, PP, Behera, PK, Mandal, AK, Behera, C, Ki, JS, Adhikary, SP, MubarakAli, D, et al
Carbohydrate polymers. 2022;:119551
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Abstract
As a significant public health hazard with several drug side effects during medical treatment, searching for novel therapeutic natural medicines is promising. Sulfated polysaccharides from algae, such as fucoidan, have been discovered to have a variety of medical applications, including antibacterial and immunomodulatory properties. The review emphasized on the utilization of fucoidan as an antiviral agent against viral infections by inhibiting their attachment and replication. Moreover, it can also trigger immune response against viral infection in humans. This review suggested to be use the fucoidan for the potential protective remedy against COVID-19 and addressing the antiviral activities of sulfated polysaccharide, fucoidan derived from marine algae that could be used as an anti-COVID19 drug in near future.
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Acute kidney injury and electrolyte disorders in COVID-19.
Nogueira, GM, Silva, NLOR, Moura, AF, Duarte Silveira, MA, Moura-Neto, JA
World journal of virology. 2022;(5):283-292
Abstract
Acute kidney injury (AKI) and electrolyte disorders are important complications of hospitalized coronavirus disease 2019 (COVID-19) patients. AKI is thought to occur due to multiple pathophysiological mechanisms, such as multiple organ dysfunction (mainly cardiac and respiratory), direct viral entry in the renal tubules, and cytokine release syndrome. AKI is present in approximately one in every ten hospitalized COVID-19 patients. The incidence rates of AKI increase in patients who are admitted to the intensive care unit (ICU), with levels higher than 50%. Additionally, renal replacement therapy (RRT) is used in 7% of all AKI cases, but in nearly 20% of patients admitted to an ICU. COVID-19 patients with AKI are considered moderate-to-severe cases and are managed with multiple interdisciplinary conducts. AKI acts as a risk factor for mortality in severe acute respiratory syndrome coronavirus 2 infection, especially when RRT is needed. Electrolyte disorders are also common manifestations in hospitalized COVID-19 patients, mainly hyponatremia, hypokalemia, and hypocalcemia. Hyponatremia occurs due to a combination of syndrome of inappropriate secretion of antidiuretic hormone and gastrointestinal fluid loss from vomiting and diarrhea. When it comes to hypokalemia, its mechanism is not fully understood but may derive from hyperaldosteronism due to renin angiotensin aldosterone system overstimulation and gastrointestinal fluid loss as well. The clinical features of hypokalemia in COVID-19 are similar to those in other conditions. Hypocalcemia is the most common electrolyte disorder in COVID-19 and seems to occur because of vitamin D deficiency and parathyroid imbalance. It is also highly associated with longer hospital and ICU stay.
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Barriers to optimal care and strategies to promote safe and optimal management of sick young infants during the COVID-19 pandemic: A multi-country formative research study.
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Journal of global health. 2022;:05023
Abstract
BACKGROUND Essential health and nutrition services for pregnant women, newborns, and children, particularly in low- and middle-income countries (LMICs), are disrupted by the COVID-19 pandemic. This formative research was conducted at five LMICs to understand the pandemic's impact on barriers to and mitigation for strategies of care-seeking and managing possible serious bacterial infection (PSBI) in young infants. METHODS We used a convergent parallel mixed-method design to explore the possible factors influencing PSBI management, barriers, and facilitators at three levels: 1) national and local policy, 2) the health systems, public and private facilities, and 3) community and caregivers. We ascertained trends in service provision and utilisation across pre-lockdown, lockdown, and post-lockdown periods by examining facility records and community health worker registers. RESULTS The pandemic aggravated pre-existing challenges in the identification of young infants with PSBI; care-seeking, referral, and treatment due to several factors at the policy level (limited staff and resource reallocation), health facility level (staff quarantine, sub-optimal treatment in facilities, limited duration of service availability, lack of clear guidelines on the management of sick young infants, and inadequate supplies of protective kits and essential medicines) and at the community level (travel restrictions, lack of transportation, and fear of contracting the infection in hospitals). Care-seeking shifted to faith healers, traditional and informal private sources, or home remedies. However, caregivers were willing to admit their sick young infants to the hospital if advised by doctors. A review of facility records showed low attendance (<50%) of sick young infants in the OPD/emergencies during lockdowns in Bangladesh, India (both sites) and Pakistan, but it gradually increased as lockdowns eased. Stakeholders suggested aspirational and pragmatic mitigation strategies. CONCLUSIONS We obtained useful insights on health system preparedness during catastrophes and strategies to strengthen services and improve utilisation regarding PSBI management. The current pandemic provides an opportunity for implementing various mitigation strategies at the policy, health system, and community levels to improve preparedness.
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Evaluation of the usefulness of vitamin D as a predictor of mortality in patients with COVID-19.
Martínez-Rodríguez, EJ, Gutiérrez-Mejía, J, Ríos-Castañeda, C, Rojas-Maya, S, Soto-Mota, A
Gaceta medica de Mexico. 2022;(1):31-35
Abstract
INTRODUCTION One of the functions of vitamin D is to regulate respiratory epithelium inflammatory response; therefore, deficiency of this vitamin in the context of COVID-19 could constitute a predictive biomarker of the disease outcome. OBJECTIVE To evaluate the usefulness of vitamin D for predicting mortality in patients with COVID-19. METHODS Observational, retrospective study in which 154 patients diagnosed with COVID-19 were included, out of whom 111 survived and 43 died. Vitamin D concentration was determined in all of them. RESULTS A log-rank p-value < 0.032 was obtained for survival when vitamin D concentration was used as a categorical variable (≤ 20 ng/mL and > 20 ng/mL). On Cox proportional analysis, age and vitamin D concentration were shown to be risk factors associated with mortality in patients with COVID-19 (age: HR = 1.036, 95% CI = 1.016-1.058, p < 0.001; vitamin D: HR (≤ 20 ng/mL and > 20 ng/mL) = 0.478, 95% CI = 0.237-0.966, p < 0.040). CONCLUSION Age and vitamin D concentration were predictive factors for mortality in COVID-19-infected patients.
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Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.
Wolfe, CR, Tomashek, KM, Patterson, TF, Gomez, CA, Marconi, VC, Jain, MK, Yang, OO, Paules, CI, Palacios, GMR, Grossberg, R, et al
The Lancet. Respiratory medicine. 2022;(9):888-899
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BACKGROUND Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING National Institute of Allergy and Infectious Diseases.
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Vitamin D regulation of immune function during covid-19.
Bikle, DD
Reviews in endocrine & metabolic disorders. 2022;(2):279-285
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Abstract
Covid-19 has to date infected a confirmed 275 million people with 5.4 million, now dead, with the count rising every day. Although the virus, SARS-CoV2, causing Covid-19 infects many cells in the body, its infection of the upper and lower respiratory tract (upper airway epithelia and pulmonary alveolar pneumocytes and macrophages) causing what is now called a cytokine storm in the lungs is the major cause of morbidity and mortality. This results from a dysregulation of the innate immune system with an outpouring of proinflammatory cytokines and chemokines leading to abnormal activation of the adaptive immune pathway. Airway epithelia constitutively expresses CYP27B1, the enzyme producing the active vitamin D metabolite, 1,25(OH)2D, and the vitamin D receptor (VDR) for which 1,25(OH)2D is the ligand. Pulmonary alveolar macrophages, on the other hand, are induced to express both CYP27B1 and VDR by various pathogens including viruses and cytokines released from infected epithelia and other immune cells. Although not demonstrated for corona viruses like SARS-CoV2, for other viruses and other respiratory pathogens activation of innate immunity leading to increased local 1,25(OH)2D production has been shown to enhance viral neutralization and clearance while modulating the subsequent proinflammatory response. Whether such will be the case for SARS-CoV2 remains to be seen, but is currently being proposed and investigated. This mini review will discuss some of the mechanisms by which vitamin D may help reduce morbidity and mortality in this devastating pandemic.