Effectiveness of Rehabilitation Interventions on Adults With COVID-19 and Post-COVID-19 Condition. A Systematic Review With Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of rehabilitation interventions for adults with COVID-19 and post COVID-19 condition (PCC) in all settings. DATA SOURCES: PubMed, EMBASE, CINAHL, Scopus, Web of Science, and Physiotherapy Evidence Database were searched from inception to December 31st, 2021. PROSPERO registration number: CRD42021258553. STUDY SELECTION: We included randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) according to the University of Alberta Evidence-based Practice Center. DATA EXTRACTION: One author extracted data using a predetermined Excel form. DATA SYNTHESIS: The meta-analysis indicates uncertain evidence about the effect of pulmonary rehabilitation and self-activities on exercise capacity (MD 65.06, 95% CI 42.87 to 87.25), respiratory function (forced expiratory volume in the first second [FEV1]: MD 0.16, 95% CI 0.05 to 0.28; FEV1/forced vital capacity [FVC]: MD 0.05, 95% CI 0.01 to 0.09; FVC: MD 0.19, 95% CI -0.03 to 0.42) and anxiety (MD -12.03, 95% CI -21.16 to -2.90) in mild COVID-19 and PCC patients. According to the narrative synthesis, including RCTs and NRSI, prone positioning seems to show improvements in vital parameters in severe COVID-19 post intensive care unit (ICU) discharge, pulmonary rehabilitation in activities of daily living, and qigong exercise and acupressure rehabilitation program, and "twist and raise" walking technique in reducing dyspnea and weakness in any degree of severity of COVID-19 and PCC. Functional electrical stimulation-cycling or early rehabilitation programs seem to support a faster recovery in patients with moderate COVID-19 after ICU discharge. Yoga and naturopathy, Mandala coloring, and respiratory exercise seem to reduce anxiety and depression in patients with moderate and mild COVID-19. Cognitive motor training seems to improve cognitive function in PCC patients. CONCLUSIONS: There is very uncertain evidence about the effect of pulmonary rehabilitation on exercise capacity and respiratory function in patients with mild COVID-19 and PCC. Further high-quality research is required to improve the certainty of evidence available to support rehabilitation's crucial role in managing COVID-19.

Chinese Medicine Meets Conventional Medicine in Targeting COVID-19 Pathophysiology, Complications and Comorbidities.

OBJECTIVE: To investigate how the National Health Commission of China (NHCC)-recommended Chinese medicines (CMs) modulate the major maladjustments of coronavirus disease 2019 (COVID-19), particularly the clinically observed complications and comorbidities. METHODS: By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology (hyperinflammations, viral replication), complications (pain, headache) and comorbidities (hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search. RESULTS: Overall, 9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8 and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively. CONCLUSION: The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.

There is nothing exempt from the peril of mutation - The Omicron spike.

The 2019 corona virus disease (COVID-19) has caused a global chaos, where a novel Omicron variant has challenged the healthcare system, followed by which it has been referred to as a variant of concern (VOC) by the World Health Organization (WHO), owing to its alarming transmission and infectivity rate. The large number of mutations in the receptor binding domain (RBD) of the spike protein is responsible for strengthening of the spike-angiotensin-converting enzyme 2 (ACE2) interaction, thereby explaining the elevated threat. This is supplemented by enhanced resistance of the variant towards pre-existing antibodies approved for the COVID-19 therapy. The manuscript brings into light failure of existing therapies to provide the desired effect, however simultaneously discussing the novel possibilities on the verge of establishing suitable treatment portfolio. The authors entail the risks associated with omicron resistance against antibodies and vaccine ineffectiveness on one side, and novel approaches and targets - kinase inhibitors, viral protease inhibitors, phytoconstituents, entry pathways - on the other. The manuscript aims to provide a holistic picture about the Omicron variant, by providing comprehensive discussions related to multiple aspects of the mutated spike variant, which might aid the global researchers and healthcare experts in finding an optimised solution to this pandemic.

Vitamin D as a Protective Factor in COVID-19 Infection in Elderly Schizophrenia and Dementia Inpatients: A Case Series.

BACKGROUND: Risk factors for severe coronavirus disease-2019 (COVID-19) infection include old age, chronic illness, and neurological conditions. In contrast, high vitamin D levels are known to augment immune activity and to reduce the severity of viral infections. Recently, a possible association between the likelihood of COVID-19 infection, COVID-19 severity, and vitamin D blood levels was reported. OBJECTIVES: To assess the possible association between vitamin D long-term supplementation and COVID-19 symptomatic severity and complications of COVID-19 infection in elderly psychiatric inpatients, a high at-risk group. METHODS: We conducted a retrospective case series study. Data of 14 elderly COVID-19 positive inpatients, presenting with dementia or schizophrenia and other medical conditions were extracted from medical records. All patients maintained a 800 IU daily dose of vitamin D prior to the infection. RESULTS: Most of the inpatients were asymptomatic or presented very few symptoms. No need for intensive care unit intervention or deaths were reported. Cognitive functioning of the patients remained unchanged. CONCLUSIONS: Pre-existing vitamin D supplementation may reinforce immunity and reduce COVID-19 severity in elderly psychiatric inpatients.

Vitamin D supplementation and COVID-19 risk: a population-based, cohort study.

PURPOSE: To analyze the associations between cholecalciferol or calcifediol supplementation, serum 25-hydroxyvitamin D (25OHD) levels and COVID-19 outcomes in a large population. METHODS: All individuals ≥ 18 years old living in Barcelona-Central Catalonia (n = 4.6 million) supplemented with cholecalciferol or calcifediol from April 2019 to February 2020 were compared with propensity score-matched untreated controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality occuring during the first wave of the pandemic. Demographical data, comorbidities, serum 25OHD levels and concomitant pharmacological treatments were collected as covariates. Associations between cholecalciferol or calcifediol use and outcome variables were analyzed using multivariate Cox proportional regression. RESULTS: Cholecalciferol supplementation (n = 108,343) was associated with slight protection from SARS-CoV2 infection (n = 4352 [4.0%] vs 9142/216,686 [4.2%] in controls; HR 0.95 [CI 95% 0.91-0.98], p = 0.004). Patients on cholecalciferol treatment achieving 25OHD levels ≥ 30 ng/ml had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19 and lower COVID-19 mortality than unsupplemented 25OHD-deficient patients (56/9474 [0.6%] vs 96/7616 [1.3%]; HR 0.66 [CI 95% 0.46-0.93], p = 0.018). Calcifediol use (n = 134,703) was not associated with reduced risk of SARS-CoV2 infection or mortality in the whole cohort. However, patients on calcifediol treatment achieving serum 25OHD levels ≥ 30 ng/ml also had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19, and lower COVID-19 mortality compared to 25OHD-deficient patients not receiving vitamin D supplements (88/16276 [0.5%] vs 96/7616 [1.3%]; HR 0.56 [CI 95% 0.42-0.76], p < 0.001). CONCLUSIONS: In this large, population-based study, we observed that patients supplemented with cholecalciferol or calcifediol achieving serum 25OHD levels ≥ 30 ng/ml were associated with better COVID-19 outcomes.

Chinese Medicine Meets Conventional Medicine in Targeting COVID-19 Pathophysiology, Complications and Comorbidities / 中国结合医学杂志

OBJECTIVE@#To investigate how the National Health Commission of China (NHCC)-recommended Chinese medicines (CMs) modulate the major maladjustments of coronavirus disease 2019 (COVID-19), particularly the clinically observed complications and comorbidities.@*METHODS@#By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology (hyperinflammations, viral replication), complications (pain, headache) and comorbidities (hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search.@*RESULTS@#Overall, 9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8 and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively.@*CONCLUSION@#The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.

Evidences suggesting a possible role of Vitamin D in COVID 19: The missing link.

The severe acute respiratory syndrome coronavirus 2 is spreading like wildfire with no specific recommended treatment in sight. While some risk factors such as the presence of comorbidities, old age, and ethnicity have been recognized, not a lot is known about who the virus will strike first or impact more. In this hopeless scenario, exploration of time-tested facts about viral infections, in general, seems to be a sound basis to prop further research upon. The fact that immunity and its various determinants (e.g., micronutrients, sleep, and hygiene) have a crucial role to play in the defense against invading organisms, may be a good starting point for commencing research into these as yet undisclosed territories. Herein, the excellent immunomodulatory, antiviral, and anti-inflammatory roles of Vitamin D necessitate thorough investigation, particularly in COVID-19 perspective. This article reviews mechanisms and evidence suggesting the role Vitamin D plays in people infected by the newly identified COVID-19 virus. For this review, we searched the databases of Medline, PubMed, and Embase. We studied several meta-analyses and randomized controlled trials evaluating the role of Vitamin D in influenza and other contagious viral infections. We also reviewed the circumstantial and anecdotal evidence connecting Vitamin D with COVID-19 emerging recently. Consequently, it seems logical to conclude that the immune-enhancing, antiviral, anti-inflammatory, and lung-protective role of Vitamin D can be potentially lifesaving. Hence, Vitamin D deserves exhaustive exploration through rigorously designed and controlled scientific trials. Using Vitamin D as prophylaxis and/or chemotherapeutic treatment of COVID-19 infection is an approach worth considering. In this regard, mass assessment and subsequent supplementation can be tried, especially considering the mechanistic evidence in respiratory infections, low potential for toxicity, and widespread prevalence of the deficiency of Vitamin D affecting many people worldwide.

Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19.

SARS-CoV-2 vaccinations have greatly reduced COVID-19 cases, but we must continue to develop our understanding of the nature of the disease and its effects on human immunity. Previously, we suggested that a dysregulated STAT3 pathway following SARS-Co-2 infection ultimately leads to PAI-1 activation and cascades of pathologies. The major COVID-19-associated metabolic risks (old age, hypertension, cardiovascular diseases, diabetes, and obesity) share high PAI-1 levels and could predispose certain groups to severe COVID-19 complications. In this review article, we describe the common metabolic profile that is shared between all of these high-risk groups and COVID-19. This profile not only involves high levels of PAI-1 and STAT3 as previously described, but also includes low levels of glutamine and NAD+, coupled with overproduction of hyaluronan (HA). SARS-CoV-2 infection exacerbates this metabolic imbalance and predisposes these patients to the severe pathophysiologies of COVID-19, including the involvement of NETs (neutrophil extracellular traps) and HA overproduction in the lung. While hyperinflammation due to proinflammatory cytokine overproduction has been frequently documented, it is recently recognized that the immune response is markedly suppressed in some cases by the expansion and activity of MDSCs (myeloid-derived suppressor cells) and FoxP3+ Tregs (regulatory T cells). The metabolomics profiles of severe COVID-19 patients and patients with advanced cancer are similar, and in high-risk patients, SARS-CoV-2 infection leads to aberrant STAT3 activation, which promotes a cancer-like metabolism. We propose that glutamine deficiency and overproduced HA is the central metabolic characteristic of COVID-19 and its high-risk groups. We suggest the usage of glutamine supplementation and the repurposing of cancer drugs to prevent the development of severe COVID-19 pneumonia.

Rationalization of Mushroom-Based Preventive and Therapeutic Approaches to COVID-19: Review.

Since December 2019, a de novo pattern of pneumonia, later named coronavirus disease 2019 (COVID-19), has caused grave upset throughout the global population. COVID-19 is associated with several comorbidities; thus, preventive and therapeutic strategies targeting those comorbidities along with the causative agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), seem imperative. In this state-of-the-art review, edible and medicinal mushrooms are featured in the treatment of SARS-CoV-2, COVID-19 pathomanifestations, and comorbid issues. Because this is not an original research article, we admit our shortcomings in inferences. Yet we are hopeful that mushroom-based therapeutic approaches can be used to achieve a COVID-free world. Among various mushroom species, reishi or lingzhi (Ganoderma lucidum) seem most suitable as anti-COVID agents for the global population.

Boswellic acids/Boswellia serrata extract as a potential COVID-19 therapeutic agent in the elderly.

The most severe cases of COVID-19, and the highest rates of death, are among the elderly. There is an urgent need to search for an agent to treat the disease and control its progression. Boswellia serrata is traditionally used to treat chronic inflammatory diseases of the lung. This review aims to highlight currently published research that has shown evidence of potential therapeutic effects of boswellic acids (BA) and B. serrata extract against COVID-19 and associated conditions. We reviewed the published information up to March 2021. Studies were collected through a search of online electronic databases (academic libraries such as PubMed, Scopus, Web of Science, and Egyptian Knowledge Bank). Several recent studies reported that BAs and B. serrata extract are safe agents and have multiple beneficial activities in treating similar symptoms experienced by patients with COVID-19. Because of the low oral bioavailability and improvement of buccal/oral cavity hygiene, traditional use by chewing B. serrata gum may be more beneficial than oral use. It is the cheapest option for a lot of poorer people. The promising effect of B. serrata and BA can be attributed to its antioxidant, anti-inflammatory, immunomodulatory, cardioprotective, anti-platelet aggregation, antibacterial, antifungal, and broad antiviral activity. B. serrata and BA act by multiple mechanisms. The most common mechanism may be through direct interaction with IκB kinases and inhibiting nuclear factor-κB-regulated gene expression. However, the most recent mechanism proposed that BA not only inhibited the formation of classical 5-lipoxygenase products but also produced anti-inflammatory LOX-isoform-selective modulators. In conclusion a small to moderate dose B. serrata extract may be useful in the enhancing adaptive immune response in mild to moderate symptoms of COVID-19. However, large doses of BA may be beneficial in suppressing uncontrolled activation of the innate immune response. More clinical results are required to determine with certainty whether there is sufficient evidence of the benefits against COVID-19.

Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still an ongoing global health crisis. Immediately after the inhalation of SARS-CoV-2 viral particles, alveolar type II epithelial cells harbor and initiate local innate immunity. These particles can infect circulating macrophages, which then present the coronavirus antigens to T cells. Subsequently, the activation and differentiation of various types of T cells, as well as uncontrollable cytokine release (also known as cytokine storms), result in tissue destruction and amplification of the immune response. Vitamin D enhances the innate immunity required for combating COVID-19 by activating toll-like receptor 2. It also enhances antimicrobial peptide synthesis, such as through the promotion of the expression and secretion of cathelicidin and ß-defensin; promotes autophagy through autophagosome formation; and increases the synthesis of lysosomal degradation enzymes within macrophages. Regarding adaptive immunity, vitamin D enhances CD4+ T cells, suppresses T helper 17 cells, and promotes the production of virus-specific antibodies by activating T cell-dependent B cells. Moreover, vitamin D attenuates the release of pro-inflammatory cytokines by CD4+ T cells through nuclear factor κB signaling, thereby inhibiting the development of a cytokine storm. SARS-CoV-2 enters cells after its spike proteins are bound to angiotensin-converting enzyme 2 (ACE2) receptors. Vitamin D increases the bioavailability and expression of ACE2, which may be responsible for trapping and inactivating the virus. Activation of the renin-angiotensin-aldosterone system (RAS) is responsible for tissue destruction, inflammation, and organ failure related to SARS-CoV-2. Vitamin D inhibits renin expression and serves as a negative RAS regulator. In conclusion, vitamin D defends the body against SARS-CoV-2 through a novel complex mechanism that operates through interactions between the activation of both innate and adaptive immunity, ACE2 expression, and inhibition of the RAS system. Multiple observation studies have shown that serum concentrations of 25 hydroxyvitamin D are inversely correlated with the incidence or severity of COVID-19. The evidence gathered thus far, generally meets Hill's causality criteria in a biological system, although experimental verification is not sufficient. We speculated that adequate vitamin D supplementation may be essential for mitigating the progression and severity of COVID-19. Future studies are warranted to determine the dosage and effectiveness of vitamin D supplementation among different populations of individuals with COVID-19.

Revisiting the Antiviral Efficacy of Terpenoids: Plausible Adjunct Therapeutics for Novel SARS-CoV-2?

Presently the world is witnessing the most devastating pandemic in the history of mankind caused by Severe Acute Respiratory Syndrome or SARS-CoV-2. This dreaded pandemic is responsible for escalated mortality rates across the globe and this is the worst catastrophe in the history of mankind. Since its outbreak, substantial scientific explorations focusing on the formulation of novel therapeutical and/or adjunct intervention against the disease are continuously in the pipeline. However, till date, no effective therapy has been approved and hence the present alarming situation urges the necessity of exploring novel, safe and efficient interventional strategies. Functionally, terpenoids are a class of secondary plant metabolites having multi facet chemical structures and are categorically documented to be the largest reservoir of bioactive constituents, predominant in nature. Intriguingly, very little is scientifically explored or reviewed in regards to the anti-CoV-2 attributes of terpenoids. The present article thus aims to revisit the antiviral efficacy of terpenoids by reviewing the current scientific literature and thereby provide an opinion on the plausibility of exploring them as potential therapeutical intervention to deal with ongoing CoV-2 pandemic.

Shedding light on vitamin D: the shared mechanistic and pathophysiological role between hypovitaminosis D and COVID-19 risk factors and complications.

Severe acute respiratory syndrome coronavirus (SARS-COV-2) is the culprit of the Coronavirus Disease (COVID-19), which has infected approximately 173 million people and killed more than 3.73 million. At risk groups including diabetic and obese patients are more vulnerable to COVID-19-related complications and poor outcomes. Substantial evidence points to hypovitaminosis D as a risk factor for severe disease, the need for ICU, and mortality. 1,25(OH)D, a key regulator of calcium homeostasis, is believed to have various immune-regulatory roles including; promoting anti-inflammatory cytokines, down regulating pro-inflammatory cytokines, dampening entry and replication of SARS-COV-2, and the production of antimicrobial peptides. In addition, there are strong connections which suggest that dysregulated 1,25(OH)D levels play a mechanistic and pathophysiologic role in several disease processes that are shared with COVID-19 including: diabetes, obesity, acute respiratory distress syndrome (ARDS), cytokine storm, and even hypercoagulable states. With evidence continuing to grow for the case that low vitamin D status is a risk factor for COVID-19 disease and poor outcomes, there is a need now to address the public health efforts set in place to minimize infection, such as lock down orders, which may have inadvertently increased hypovitaminosis D in the general population and those already at risk (elderly, obese, and disabled). Moreover, there is a need to address the implications of this evidence and how we may apply the use of cheaply available supplementation, which has yet to overcome the near global concern of hypovitaminosis D. In our review, we exhaustively scope these shared pathophysiologic connections between COVID-19 and hypovitaminosis D.

["Long-haul COVID": An opportunity to address the complexity of post-infectious functional syndromes]. / « COVID long ¼ : une opportunité pour approcher la complexité des syndromes fonctionnels post-infectieux.

In this work, we address the issue of prolonged symptoms following an infection by SARS-CoV-2, labeled "long COVID". This clinically unspecific syndrome must be put in perspective with the post-infectious syndromes known for a long time but ultimately poorly understood and little studied, qualified, for lack of convincing arguments for a unambiguous pathophysiology and better terms, as functional somatic syndromes. The clinical implications for clinical care ("holistic" work-up and care of patients), for research (need for truly "bio-psycho-social" investigations), and the social implications of "long COVID" (social construction of the syndrome through the experiences of patients exposed on social networks, inequalities in the face of the disease and its socioeconomic consequences) are considered. "Long COVID" must be view, because of its expected prevalence, as an opportunity to address the complexity of post-infectious (functional) syndromes, their risk factors, and the biological, psychological and social mechanisms underlying them.

Regarding pandemics: Ibn Jatima from Almería anticipates the physiopathological concept of multi-organ failure in the 14th century.

In 1348, a pandemic known as Black Death devastated humanity and changed social, economic and geopolitical world order, as is the current case with SARS-CoV-2 coronavirus. The doctor of the Nasrid Kingdom of Granada, Ibn-Jatima from Almeria, wrote "Treatise on the Plague", in which it may be found epidemiological and clinical similarities between both plagues. In the context of Greco-Arab medicine, he discovered respiratory and contact contagion of Pestis and attributed its physiopathology to a lack of pulmonary cooling of the innate heat, generated in the heart and carried by the blood humor. The process described was equivalent to the oxygen transport system. Furthermore, it was supposed to generate toxic residues, such as free radicals, leading to an irreversible multiple organ failure (MOF), considered a mortality factor as in Covid-19. Due to its similitude, it would be the first antecedent of the MOF physiopathological concept, a finding that enriches the scientific and historical heritage of our clinical specialty.

The effect of acupoint herbal patching on the quality of life of patients recovering from COVID-19: A protocol for systematic review and meta analysis.

BACKGROUND: There is a worldwide outbreak of COVID-19, and as the number of patients increases, an increasing number of patients are recovering. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of acupoint herbal patching on the life of patients recovering from COVID-19. METHODS: The following electronic databases will be searched from the respective dates of database inception to April 20, 2021: The Cochrane Library, Web of Science, EMBASE, MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang database, the Chinese Scientific Journal Database (VIP), and other sources. All published randomized controlled trials in English or Chinese related to acupoint herbal patching for COVID-19 will be included. The primary outcome was the timing of the influence of acupoint herbal patching on the quality of life of convalescent patients. Secondary outcomes were accompanying symptoms (such as myalgia, expectoration, stuffiness, runny nose, pharyngalgia, anhelation, chest distress, dyspnea, crackles, headache, nausea, vomiting, anorexia, diarrhea) disappearance rate, negative COVID-19 results rate on two consecutive occasions (not on the same day), average hospitalization time, clinical curative effect, and improved quality of life. RESULTS: The main purpose of this systematic review protocol was to assess the effectiveness and safety of acupoint herbal patching therapy for treating patients recovering from COVID-19. CONCLUSION: The conclusion of our study will provide evidence to judge whether acupoint herbal patching is an effective intervention for the quality of life in patients recovering. PROSPERO REGISTRATION NUMBER: CRD42021246550.

Endocrine and metabolic aspects of COVID-19.

The paper presents the theoretical considerations on the role of endocrine and metabolic alterations accompanying COVID-19 infection. These alterations may be presumed on the basis of the following two observations. Firstly, the virus SARS-CoV-2 responsible for the COVID-19 infection uses an important renin-angiotensin system (RAS) element - angiotensin-converting enzyme 2 (ACE2) - as a receptor protein for entry into target cells and, in consequence, disturbs the function of the main (circulating) renin-angiotensin-aldosterone system (RAAS) and of the local renin-angiotensin system localized in different tissues and organs. The binding of SARS-CoV-2 to ACE2 leads to the downregulation of this enzyme and, in the aftermath, to the excess of angiotensin II and aldosterone. Thus, in the later stage of COVID-19 infection, the beneficial effects of ACEI and ARB could be presumed. It is hypothesized that the local RAS dysregulation in the adipose tissue is the main cause of the negative role of obesity as a risk factor of severe outcome of the COVID-19 infection. Secondly, the outcome of COVID-19 strongly depends on the age of the patient. Age-related hormonal deficiencies, especially those of melatonin and dehydroepiandrosterone, may contribute to morbidity/mortality in older people. The usefulness of melatonin and angiotensin converting enzyme inhibitors/angiotensin receptor 1 blockers (the latter only in later phases of the infection) as adjuvant drugs is probable but needs thorough clinical trials.

Assessment of Body Composition and Dietary Intake in Nursing-Home Residents: Could Lessons Learned from the COVID-19 Pandemic Be Used to Prevent Future Casualties in Older Individuals?

The population of older adults, especially those living in the nursing homes, is growing. The sedentary lifestyle and possible poor nutrition in nursing homes place residents (NHRs) at risk for body composition impairments, malnutrition, and, subsequently, numerous chronic diseases. The aim of this study was to assess body composition (including body fluids) and dietary intake in NHRs. The association between osteosarcopenic adiposity syndrome (OSA) and its components, osteopenic adiposity (OA), sarcopenic adiposity (SA), and adiposity-only (AD), and specific macro- and micro-nutrients was evaluated as well. The study included 84 participants (82.1% women), aged 65.3-95.2 years. Body composition was assessed with an advanced bioelectrical impedance device BIA-ACC® and dietary intake was assessed via 24-h recall and analyzed using "Nutrition" software. The majority (95%) of participants were overweight with a high body fat and low muscle and bone mass, leading to a high prevalence of OSA (>50%), OA (13%), and AD (26%). There were only a few participants with SA, and they were not analyzed. The highest extracellular water/total body water ratio was observed in the OSA participants, indicating a heightened inflammatory state. Participants in all three body composition categories had a similar nutrient intake, with protein, fiber, omega-3 fatty acids, and almost all micronutrients being far below recommendations. In conclusion, a high prevalence of OSA among NHRs accompanied by a poor dietary intake, could place these residents at a very high risk for COVID-19 infections. Therefore, optimization of body composition and nutritional status should be included along with standard medical care in order to provide better health maintenance, particularly in the COVID-19 era.

Sulforaphane inhibits the expression of interleukin-6 and interleukin-8 induced in bronchial epithelial IB3-1 cells by exposure to the SARS-CoV-2 Spike protein.

BACKGROUND: A key clinical feature of COVID-19 is a deep inflammatory state known as "cytokine storm" and characterized by high expression of several cytokines, chemokines and growth factors, including IL-6 and IL-8. A direct consequence of this inflammatory state in the lungs is the Acute Respiratory Distress Syndrome (ARDS), frequently observed in severe COVID-19 patients. The "cytokine storm" is associated with severe forms of COVID-19 and poor prognosis for COVID-19 patients. Sulforaphane (SFN), one of the main components of Brassica oleraceae L. (Brassicaceae or Cruciferae), is known to possess anti-inflammatory effects in tissues from several organs, among which joints, kidneys and lungs. PURPOSE: The objective of the present study was to determine whether SFN is able to inhibit IL-6 and IL-8, two key molecules involved in the COVID-19 "cytokine storm". METHODS: The effects of SFN were studied in vitro on bronchial epithelial IB3-1 cells exposed to the SARS-CoV-2 Spike protein (S-protein). The anti-inflammatory activity of SFN on IL-6 and IL-8 expression has been evaluated by RT-qPCR and Bio-Plex analysis. RESULTS: In our study SFN inhibits, in cultured IB3-1 bronchial cells, the gene expression of IL-6 and IL-8 induced by the S-protein of SARS-CoV-2. This represents the proof-of-principle that SFN may modulate the release of some key proteins of the COVID-19 "cytokine storm". CONCLUSION: The control of the cytokine storm is one of the major issues in the management of COVID-19 patients. Our study suggests that SFN can be employed in protocols useful to control hyperinflammatory state associated with SARS-CoV-2 infection.