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COVID-19: A Brief Overview on the Role of Vitamins Specifically Vitamin C as Immune Modulators and in Prevention and Treatment of SARS-Cov-2 Infections
Abstract
In December 2019 a pandemic of acute respiratory distress syndromes occurs in Wuhan, china, the early evidence suggests this may be due to exposure to local sea foods in china. The pathogen was isolated from Chinese patients and designated as severe acute respiratory syndrome corona virus 2 (SARS-COV-2). COVID-19 mainly affects lungs by producing respiratory predominant symptoms like fever, cough, flu and dyspnea. As SARS-Cov-2 firstly find a mechanism to escape the immune system of humans and animals followed by a huge release of cytokines named as cytokine storms and the hyper activation of the other immune system responses. To avoid these conditions in any type of viral infections such as in SARS-Cov-2 infections and influenza virus induce lung injury vitamin D is now is recently considered as proposed therapy. Vitamin C acts as strong antioxidant and help to scavenge all the damaged species that is why vitamin C is regarded helpful in SARS-Cov-2 and other viral infections. Many findings from different clinical studies show that vitamin C when administrated orally can reduce SAR-Cov-2 and other viral infection. Taking vitamin C intravenously has also profound effect on the reduction of viral infections. As health care workers and professional are risk community for
... An increase in ROS will activate the redox transcription factors and thus lead to the release of more pro-inflammatory factors (40). Vitamins C and E were determined as great scavengers for these ROS (41). The negative correlation observed in this study between Zn and SOD is in contrast to that reported by Maradi R et al., who observed a significant correlation between them reporting the strong effect of Zn on SOD (42). ...
... An increase in ROS will activate the redox transcription factors and thus lead to the release of more pro-inflammatory factors (40). Vitamins C and E were determined as great scavengers for these ROS (41). The negative correlation observed in this study between Zn and SOD is in contrast to that reported by Maradi R et al., who observed a significant correlation between them reporting the strong effect of Zn on SOD (42). ...
Background: SARS-CoV-2 infection can cause significant alterations in our lives. Oxidative stress (OS) has been proposed to play a major role in COVID-19 pathogenesis, and the determination of OS biomarkers provides insight into disease severity. Methods: The study was conducted during the second wave of the pandemic in 2020. Fifty blood samples were collected from patients admitted to one of the COVID-19 isolation centers in Baghdad, Iraq. The samples were subdivided into 25 patients admitted to the intensive care unit (ICU) and 25 non-ICU patients, compared to 25 healthy controls. All participants were aged 35-52 years. Results: The study showed that the mean (±SD) serum total oxidant status (TOS) and malondialdehyde (MDA) levels were significantly increased (p< 0.001) in the ICU group compared to the control and non-ICU groups. Conversely, the levels of serum total antioxidant capacity (TAC) and serum antioxidative enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase, and glutathione (GSH) were significantly decreased (p< 0.001) in the ICU group compared to both the control and non-ICU groups. Serum zinc levels were significantly decreased (p< 0.001) in both ICU and non-ICU groups compared to the control group, while serum selenium (Se), copper (Cu), and vitamins C and E were significantly decreased (p< 0.001) in the ICU group compared to both the control and non-ICU groups. Conclusion: The presence of OS biomarkers in the sera of COVID-19 patients offers a potential new approach for the treatment of this disease.
... The increase the oxidative stress by typically activating phagocytes which produce the ROS [21].Vitamin C and E being renowned antioxidants and to some extent when vitamin A scavenge for the ROS and counteract their effects, in this process of scavenging lead to the level of these vitamins in the body becomes depleted [22]. Vitamins C and E are found in the body and lead to helpful in cytokine storms and cellular injury and these vitamins are the strong antioxidants and decrease the ROS and these vitamins as helpful in SARS-Cov-2 and other viral infections [23].The decrease level of these vitamins are showed in this study is owing to their role in scavenging ROS as they are being used up in the process and findings are similar to other reports [24].The antioxidant defenses was detected in the COVID-19 patients as evidenced by the levels of vitamin A, C and E that were the largely interval and all the in COVID-19 patients, their median value in the vitamin C corresponds to the hypovitaminosis C [25]. Our results that vitamin C,E and Adecrease in COVID-19 patients and similar to other reported [26,27].Infact, the intravenous administration only has able torestore high-level ascorbic acid plasma concentration [28].The high doses of vitamin C can help to decrease the -cytokines storm‖ [29].Our results also showed lower level the GSH,GPx, SOD and catalase in COVID-19 patientscompere with controls group andsimilar to other study, the reports work on patients with Epstein-Barr virus, decreased activities of GSH, SOD and GPx [30]. ...
This study is concerned with COVID-19pandemic and subjects were divided into three main groups honey consumed of COVID-19 patients(n = 90),without honey consumed of COVID-19 patients(n = 30) and control group(n = 30). The determine patients in the city of Najaf during the period between July 2020 to august 2020.Patients were identified using a PCR technique, after which a 5 milliliter was withdrawnon the first day to identify(VitaminA,VitaminC,VitaminE,GSH,GPx,SOD,CAT,MDA) and then repeat the process of determining the variables every seven days.In addition to giving COVID-19patients a kilogram of honey divided into different quantities and different times and compere with second group (without honey consumed of COVID-19patients)and examined by PCR technique.These variables measured the concentration by using assay (ELISA) technique and spectrophotometer instrument. All above variables there was a significant difference and correlation in patients (p˂0.05).Also results showed changes in concentrations levels variablesof honey consumed COVID-19 a significant difference between the mean value in patients (p˂0.05)but little changesin concentrations variableswithout honey consumed of COVID-19 patients a significant difference between the mean value in patients (p˂0.05).The results showed the effect of honey consumed of COVID-19 patients over timeon patients three times a day and the patients are examined byPCR test showed Negative which more than 14 days.
... The findings are no incidence of death and a shorter mean hospital stay than untreated COVID-19 patients [13]. Besides, the Shanghai Medical Table 1 Role of vitamin C in the modulation of several complications [69] Complications ...
Background
The outbreak of coronavirus infectious disease-2019 (COVID-19) is globally deemed a significant threat to human life. Researchers are searching for prevention strategies, mitigation interventions, and potential therapeutics that may reduce the infection’s severity. One such means that is highly being talked in online and in social media is vitamin C.
Main text
Vitamin C is a robust antioxidant that boosts the immune system of the human body. It helps in normal neutrophil function, scavenging of oxidative species, regeneration of vitamin E, modulation of signaling pathways, activation of pro-inflammatory transcription factors, activation of the signaling cascade, regulation of inflammatory mediators, and phagocytosis and increases neutrophil motility to the site of infection. All of these immunological functions are required for the prevention of COVID-19 infection.
Conclusion
Considering the role of vitamin C, it would be imperative to administrate vitamin C for the management of severe COVID-19. However, there is no specific clinical data available to confirm the use of vitamin C in the current pandemic.
... Vitamins C and E act as strong antioxidants and help to scavenge the ROS, which is why Jan et al. 26 regarded these vitamins as helpful in SARS-Cov-2 and other viral infections. The reduced level of these vitamins observed in this study is owing to their role in scavenging ROS as they are being used up in the process. ...
Introduction
The COVID-19 is a pandemic caused by SARS-CoV-2 which has infected over 74 million people, killing more than 1,600,000 million people around the world as of 17th December 2020. Accumulation of free radicals coupled by weakened antioxidant system leads to oxidative stress, which will further worsen respiratory diseases, COVID-19 inclusive. This study aimed to examine the levels of some antioxidants and oxidative stress markers in COVID-19 patients.
Methods
This was a cross-sectional comparative study in which 50 COVID-19 symptomatic patients who were on admission at the COVID-19 isolation center in Jigawa, Northwestern Nigeria, were recruited. Twenty one (21) apparently healthy individuals were included as controls. Levels of antioxidant trace elements (Se, Zn, Mg, Cu and Cr), 8-isoprostaglandin F2 alpha and malondialdehyde in the plasma and erythrocytes activity of glutathione, glutathione peroxidase, superoxide dismutase and catalase were determined.
Results
The plasma concentrations of vitamins A, C and E were significantly lower (p < 0.001) in COVID-19 patients than controls. Activities of glutathione, glutathione peroxidase, catalase and superoxide dismutase were lower in COVID-19 subjects than controls (p < 0.001). The concentrations of Se, Zn, Mg and Cu were significantly lower (p < 0.001; p = 0.039; p < 0.001; and p < 0.001), respectively, in COVID-19 patients than controls, while chromium showed no significant difference (p = 0.605). Oxidative stress marker, 8-isoprostaglandin F2 alpha, was significantly higher (p = 0.049), while malondialdehyde was lower (p < 0.001) in COVID-19 patients than controls.
Conclusion
In conclusion, COVID-19 patients are prone to depleted levels of antioxidant substances due to their increase utilization in counterbalancing the negative effect of free radicals. Furthermore, COVID-19 infection with other comorbidities, such as malaria, hypertension and diabetes, are at higher risk of developing oxidative stress.
... Many Vitamins such as C, D, and E have been found to improve immunity, as Vitamin D increases resistance to cell walls and protect the cytoplasm and so the consumption of fruits and vegetables It plays a pivotal role in preventing this epidemic [12]. Vitamin C has recently become one of the most appropriate treatments as it works as a powerful antioxidant and helps protect against cell damage caused by many types of microorganisms, and this is what made it effective against SARS and other viral infections, Several results of various clinical studies showed that giving Vitamin C orally reduces the incidence of SARS, and giving it intravenously is also beneficial against viral infections, and specialists believe that the treatment of Covid-19 should include Vitamin C as prevention and treatment in normal cases, but in the Covid-19 case, giving a high dose intravenously would be the best option [13].In a study conducted in Wuhan -China on Covid-19 patients to find a possible relationship between blood groups and infection rate, it was found that the blood groups most susceptible to infection were group A and the least infections were in patients of group O, while another study confirmed that the rates of infections according to blood groups were group A is the most and least of group AB [14,15]. Elderly patients often have chronic diseases conditions and show distinct symptoms when infected with Covid-19, as they must be taken care of more than young infected people in terms of observation, nursing care and comprehensive treatment [16]. ...
This study has been done upon (296) recovered Covid-19 patients, 189 (63.9%) males and 107 (36.1%) females. The study found that blood group O was the most vulnerable to infection with a percentage (59.8%), followed by group (A) (35.8%), AB (2.4%) and finally group B (2%). The study also showed that (71.6%) of the infected people consume citrus fruits only once a week, (61.1%) do not consume fish, (86.1%) are used to shaking hands and approaching others when meeting others, (95.3%) do not expose their bodies to direct sunlight, and (90.2%) do not wear masks and gloves outside the home.Material and method: questionnaire was used with direct interview,required data obtained from medical reports then a statistical analysis was performed.Results: Most patients from age groups (25-40) years, blood group B is the least vulnerable to infection, most people are accustomed to rapprochement and closeness. Patients were usually expose their bodies to sun light as a natural source of Vitamin D.Conclusion:main cause of covid-19 spread is closeness, blood group B is the least vulnerable to infection, healthy nutrition and cleanness are very necessary to prevent covid-19 spread.
Pendahuluan: Virus corona atau COVID-19 telah menyebar sangat cepat serta luas sehingga menginfeksi setiap negara diseluruh dunia dan akibatnya pandemic global berlangsung sampai sekarang. Tidakan pecegahan COVID-19 ini diantaranya ialah memberi edukasi serta sosialisasi untuk masyarakat agar mematuhi protokol kesehatan dan meningkatkan daya tahan tubuh atau sistem imun. Banyak hal yang dapat di lakukan untuk meningkatkan sistem imun, salah satunya dengan megkonsumsi vitamin C. Metode: Jenis penelitian ini adalah penelitian deskriptif kuantitatif dengan metode survei yang dalam teknik pengambilan sampelnya menggunakan sampling kuota, untuk mengumpulkan data menggunakan alat bantu kuesioner. Hasil: Hasil analisis univariat didapatkan bahwa tingkat pengetahuan reponden dalam kategori baik sebesar 53,79%. Kategori cukup sebesar 29,65% dan kategori kurang sebesar 16,55%. Hasil analisis bivariat didapatkan bahwa terdapat hubungan antara usia dengan tingkat pengetahuan masyarakat desa welahan tentang penggunaan vitamin C sebagai pencegah COVID-19 (p = 0,036), tidak terdapat hubungan antara jenis kelamin dengan tingkat pengetahuan masyarakat desa welahan tentang penggunaan vitamin C sebagai pencegah COVID-19 (p = 0,873), terdapat hubungan pendidikan dengan tingkat pengetahuan masyarakat desa welahan tentang penggunaan vitamin C sebagai pencegah COVID-19 (p = 0,016). Simpulan: Kesimpulan penelitian ini adalah terdapat hubungan antara karakteristik usia dan pendidikan dengan tingkat pengetahuan masyarakat desa welahan tentang penggunaan vitamin C sebagai pencegah COVID-19 dan tidak terdapat hubungan jenis kelamin dengan tingkat pengetahuan masyarakat desa welahan tentang penggunaan vitamin C sebagai pencegah COVID-19.
COVID-19 is a rapidly spreading disease, which has caught the world by surprise. Millions of people suffer from illness, and the mortality rates are dramatically high. Currently, there is no specific and immediate treatment for this disease. Remedies are limited to supportive regiments and few antiviral and anti-inflammatory drugs. The lack of a definite cure for COVID-19 is the reason behind its high mortality and global prevalence. COVID-19 can lead to a critical illness with severe respiratory distress and cytokine release. Increased oxidative stress and excessive production of inflammatory cytokines are vital components of severe COVID-19. Micronutrients, metalloids, and vitamins such as iron, manganese, selenium, Zinc, Copper, vitamin A, B family, and C are among the essential and trace elements that play a pivotal role in human nutrition and health. They participate in metabolic processes that lead to energy production. In addition, they support immune functions and act as antioxidants. Therefore, maintaining an optimal level of micronutrients intake, particularly those with antioxidant activities, is essential to fight against oxidative stress, modulate inflammation, and boost the immune system. Therefore, these factors could play a crucial role in COVID-19 prevention and treatment. In this review, we aimed to summarize antiviral properties of different vitamins and minerals. Moreover, we will investigate the correlation between them and their effects in COVID-19 patients.
Background
Virus is a tiny agent, around one-hundredth the size of a bacterium which can infect cells of plants and animals. Seven coronaviruses are known to infect humans, three of them are serious, namely, SARS (severe acute respiratory syndrome, China, 2002), MERS (Middle East respiratory syndrome, Saudi Arabia, 2012), and SARS-CoV-2 (COVID-19) (2019-2020).SARS-CoV, and MERS-CoV belong to betacoronaviruses (betaCoVs).
Objective
In this mini review, we want to consider the important vitamin D and C, especially plants containing these two vitamins in fight against COVID-19.
Methods
The manuscript includes review articles, randomized control experiments, analytical studies and observations, which have been gathered from different sources such as Google Scholar, Scopus, Science Direct and PubMed. A review of the literature was carried out using the keywords such as vitamin D, vitamin C, COVID-19, influenza, Plant, and Coronaviruses.
Results
Various sources of vitamin D for humans are food, dietary supplements and the skin by exposure to 7-dehydrocholesterol to ultraviolet light. There are some new findings on influence vitamin D in prevent and control of influenza and COVID-19. Vitamin D may play roles in preventing influenza and covid-19 by production of large quantities of IL-1 and IL-6, or modulating the production of the interleukins.
Conclusion
Vitamin D deficiency is a potential link between respiratory infection and immune evasion, and vitamin D is a pleiotropic factor known to modulate immune response against pathogen.
Coronavirus Disease 2019 (CoViD-19) is the third type of coronavirus disease after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) that appears in human population from the past two decades. It is highly contagious and rapidly spread in the human population and compelled global public health institutions on high alert. Due to genetic similarity of this novel coronavirus 2019 with bat virus its emergence from bat to humans is possible. The virus survive in the droplets of coughing and sneezing and spread around the large areas through infected person resulting in its rapid spread among people. Clinical symptoms of CoViD-19 include fever, dry cough, dyspnea, loose stool, nausea and vomiting. The present review discuss the origin of CoViD-19, its rapid spread, mortality rate and recoveries ratio around the world. Since its origin from Wuhan, the CoViD-19 spread very rapidly all across the countries, on April 17, 2020 this disease has affected 210 countries of the globe. The data obtained showed over 2.4 million confirmed cases of CoViD-19. Higher mortality rate was found in Algeria and Belgium as 15% and 13.95%, respectively. Lower mortality rate was found in Qatar 0.17% and Singapore 0.2%. Recovery versus deceased ratio showed that recovery was 68, 59 and 35 times higher than the death in Singapore, Qatar and Thailand respectively. It is concluded that 2019-novel corona virus is a zoonotic pathogen similar to MERS and SARS. Therefore, a barrier should be maintained between and across the human, household and wild animals to avoid such pandemics.
Infection with avian influenza A H5N1 virus results in acute lung injury (ALI) and has a high mortality rate (52.79%) because there are limited therapies available for treatment. Drug repositioning is an economical approach to drug discovery. We developed a method for drug repositioning based on high-throughput RNA sequencing and identified several drugs as potential treatments for avian influenza A H5N1 virus. Using high-throughput RNA sequencing, we identified a total of 1,233 genes differentially expressed in A549 cells upon H5N1 virus infection. Among these candidate genes, 79 drug targets (corresponding to 59 approved drugs) overlapped with the DrugBank target database. Twenty-two of the 41 commercially available small-molecule drugs reduced H5N1-mediated cell death in cultured A549 cells, and fifteen drugs that protected A549 cells when administered both pre- and post-infection were tested in an H5N1-infection mouse model. The results showed significant alleviation of acute lung injury by amitriptyline HCl (an antidepressant drug), flavin adenine dinucleotide (FAD; an ophthalmic agent for vitamin B2 deficiency), azacitidine (an anti-neoplastic drug) and calcitriol (an active form of vitamin D). All four agents significantly reduced the infiltrating cell count and decreased the lung injury score in H5N1 virus-infected mice based on lung histopathology, significantly improved mouse lung edema by reducing the wet-to-dry weight ratio of lung tissue and significantly improved the survival of H5N1 virus-infected mice. This study not only identifies novel potential therapies for influenza H5N1 virus-induced lung injury but also provides a highly effective and economical screening method for repurposing drugs that may be generalizable for the prevention and therapy of other diseases.
A novel viral respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for an epidemic of the coronavirus disease 2019 (COVID-19) in cases in China and worldwide. Four full-term, singleton infants were born to pregnant women who tested positive for COVID-19 in the city of Wuhan, the capital of Hubei province, China, where the disease was first identified. Of the three infants, for who consent to be diagnostically tested was provided, none tested positive for the virus. None of the infants developed serious clinical symptoms such as fever, cough, diarrhea, or abnormal radiologic or hematologic evidence, and all four infants were alive at the time of hospital discharge. Two infants had rashes of unknown etiology at birth, and one had facial ulcerations. One infant had tachypnea and was supported by non-invasive mechanical ventilation for 3 days. One had rashes at birth but was discharged without parental consent for a diagnostic test. This case report describes the clinical course of four live born infants, born to pregnant women with the COVID-19 infection.
Abstract An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.
As COVID-19 continues to spread worldwide, George Winter discusses emergency strategies, lessons from past epidemics and the vital role that healthcare managers can play in shaping responses to infectious diseases in today's global society.
Vitamin D deficiency has been reported to be associated with respiratory tract infection (RTI). However, evidence regarding the effects of vitamin D supplementation on susceptibility of infants to RTI is limited. In this prospective birth cohort study, we examined whether vitamin D supplementation reduced RTI risk in 2,244 infants completing the follow‐up from birth to 6 months of age. The outcome endpoint was the first episode of paediatrician‐diagnosed RTI or 6 months of age when no RTI event occurred. Infants receiving vitamin D supplements at a daily dose of 400–600 IU from birth to the outcome endpoint were defined as vitamin D supplementation and divided into four groups according to the average frequency of supplementation: 0, 1–2, 3–4, and 5–7 days/week. We evaluated the relationship between vitamin D supplementation and time to the first episode of RTI with Kaplan–Meier plots. The associations of vitamin D supplementation with infant RTI, lower RTI (LRTI), and RTI‐related hospitalization were assessed using modified Poisson regression. The median time to first RTI episode was 60 days after birth (95% CI [60, 90]) for infants without supplementation and longer than 6 months of age for infants with supplementation (p < .001). We observed inverse trends between supplementation frequency and risk of RTI, LRTI, and RTI‐related hospitalization (p for trend < .001), with the risk ratios in the 5–7 days/week supplementation group of 0.46 (95% CI [0.41, 0.50]), 0.17 (95% CI [0.13, 0.24]), and 0.18 (95% CI [0.12, 0.27]), respectively. These associations were significant and consistent in a subgroup analysis stratified by infant feeding.
In December 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in Wuhan, Hubei Province, China and spread across China and beyond. On February 12, 2020, WHO officially named the disease caused by the novel coronavirus as Coronavirus Disease 2019 (COVID-19). Since most COVID-19 infected patients were diagnosed with pneumonia and characteristic CT imaging patterns, radiological examinations have become vital in early diagnosis and assessment of disease course. To date, CT findings have been recommended as major evidence for clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the etiology, epidemiology, and clinical symptoms of COVID-19, while highlighting the role of chest CT in prevention and disease control. A full translation of this article in Chinese is available.
Importance
In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
Objective
To describe the epidemiological and clinical characteristics of NCIP.
Design, Setting, and Participants
Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020.
Exposures
Documented NCIP.
Main Outcomes and Measures
Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked.
Results
Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 10⁹/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0).
Conclusions and Relevance
In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome-related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1–4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5–7. Here we report the identification and characterization of a novel coronavirus (2019-nCoV) which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started from 12 December 2019, has caused 2,050 laboratory-confirmed infections with 56 fatal cases by 26 January 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The 2019-nCoV virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.
Mechanical ventilation with hyperoxia is the major supportive measure to treat patients with acute lung injury and acute respiratory distress syndrome (ARDS). However, prolonged exposure to hyperoxia can induce oxidative inflammatory lung injury. Previously, we have shown that high levels of airway high-mobility group box 1 protein (HMGB1) mediate hyperoxia-induced acute lung injury (HALI). Using both ascorbic acid (AA, also known as vitamin C) and sulforaphane (SFN), an inducer of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), we tested the hypothesis that dietary antioxidants can mitigate HALI by ameliorating HMGB1-compromised macrophage function in phagocytosis by attenuating hyperoxia-induced extracellular HMGB1 accumulation. Our results indicated that SFN, which has been shown to attenute HALI in mice exposed to hyperoxia, dose-dependently restored hyperoxia-compromised macrophage function in phagocytosis (75.9 ± 3.5% in 0.33 µM SFN versus 50.7 ± 1.8% in dimethyl sulfoxide (DMSO) control, p < 0.05) by reducing oxidative stress and HMGB1 release from cultured macrophages (47.7 ± 14.7% in 0.33 µM SFN versus 93.1 ± 14.6% in DMSO control, p < 0.05). Previously, we have shown that AA enhances hyperoxic macrophage functions by reducing hyperoxia-induced HMGB1 release. Using a mouse model of HALI, we determined the effects of AA on hyperoxia-induced inflammatory lung injury. The i.p. administration of 50 mg/kg of AA to mice exposed to 72 h of ≥98% O2 significantly decreased hyperoxia-induced oxidative and nitrosative stress in mouse lungs. There was a significant decrease in the levels of airway HMGB1 (43.3 ± 12.2% in 50 mg/kg AA versus 96.7 ± 9.39% in hyperoxic control, p < 0.05), leukocyte infiltration (60.39 ± 4.137% leukocytes numbers in 50 mg/kg AA versus 100 ± 5.82% in hyperoxic control, p < 0.05) and improved lung integrity in mice treated with AA. Our study is the first to report that the dietary antioxidants, ascorbic acid and sulforaphane, ameliorate HALI and attenuate hyperoxia-induced macrophage dysfunction through an HMGB1-mediated pathway. Thus, dietary antioxidants could be used as potential treatments for oxidative-stress-induced acute inflammatory lung injury in patients receiving mechanical ventilation.
Background:
The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP.
Methods:
We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number.
Results:
Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9).
Conclusions:
On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).
Background:
An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date.
Methods:
In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done.
Findings:
From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36-66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3-6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6-10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats.
Interpretation:
Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions.
Funding:
The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).
Background:
A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients.
Methods:
All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.
Findings:
By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.
Interpretation:
The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies.
Funding:
Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
Sepsis, a life-threatening organ dysfunction due to a dysregulated host response to infection, is a leading cause of morbidity and mortality worldwide. Decades of research have failed to identify any specific therapeutic targets outside of antibiotics, infectious source elimination, and supportive care. More recently, vitamin C has emerged as a potential therapeutic agent to treat sepsis. Vitamin C has been shown to be deficient in septic patients and the administration of high dose intravenous as opposed to oral vitamin C leads to markedly improved and elevated serum levels. Its physiologic role in sepsis includes attenuating oxidative stress and inflammation, improving vasopressor synthesis, enhancing immune cell function, improving endovascular function, and epigenetic immunologic modifications. Multiple clinical trials have demonstrated the safety of vitamin C and two recent studies have shown promising data on mortality improvement. Currently, larger randomized controlled studies are underway to validate these findings. With further study, vitamin C may become standard of care for the treatment of sepsis, but given its safety profile, current treatment can be justified with compassionate use.
Emerging evidence has shown that vitamin D deficiency may be related with community-acquired pneumonia (CAP), but individually published studies showed inconclusive results. The aim of this study was to quantitatively summarize the association between vitamin D and the CAP.
We conducted this meta-analysis though a systematic literature search of PubMed, Medline, and EMBASE up to 31 September 2018 with the following keywords ‘vitamin D’ or ‘cholecalciferol’ or ‘25-hydroxyvitamin D’ or ‘25(OH)D’ in combination with ‘community-acquired pneumonia’ or ‘CAP’ or ‘pneumonia’ with no limitations. This meta-analysis was performed following the guidelines of Meta-analysis of Observational Studies in Epidemiology. The association between vitamin D levels and CAP were measured as odds ratio (OR) and weighted mean difference (WMD). Results were combined using a random-effect or a fix-effect meta-analysis, and sensitivity analyses were conducted to explore potential factors.
Eight observational studies involving 20,966 subjects were included. In this meta-analysis, CAP patients with vitamin D deficiency (serum 25(OH)D levels <20 ng/mL) experienced a significantly increased risk of CAP (odds ratio (OR) = 1.64, 95% confidence intervals (CI): 1.00, 2.67), and an obvious decrease of −5.63 ng/mL (95% CI: −9.11, −2.14) in serum vitamin D was demonstrated in CAP patients. Sensitivity analysis showed that exclusion of any single study did not materially alter the overall combined effect.
The evidence from this meta-analysis indicates an association between vitamin D deficiency and an increased risk of CAP patients. However, well-designed trails are required to determine the explicit effect of vitamin D supplementation.
Calcitriol [1,25(OH)2D3] is usually investigated in studies on the preventive effect of activated vitamin D against interstitial pneumonia. Although cholecalciferol (vitamin D3) can be easily obtained in the diet and has a longer half-life than calcitriol, there have been few investigations of its effect on interstitial pneumonia. We used human pulmonary fibroblast cell lines (HPFCs) and a mouse model of bleomycin-induced pulmonary fibrosis to evaluate whether vitamin D3 was activated in the lungs and had a preventive effect against interstitial pneumonia. Expression of the vitamin D receptor gene and genes for enzymes metabolizing vitamin D was evaluated in two HPFCs, and the suppressive effect of vitamin D3 on induction of inflammatory cytokines was also assessed. Gene expression of the vitamin D receptor and vitamin D-metabolizing enzymes was observed in both human pulmonary fibroblast cell lines. Vitamin D3 suppressed bleomycin-induced expression of inflammatory cytokines and fibrosis markers by the HPFCs. In mice, symptoms of bleomycin-induced pulmonary fibrosis were improved and expression of fibrosis markers/fibrosis inducers was decreased by a high vitamin D3 diet. Vitamin D3 is activated locally in lung tissues, suggesting that high dietary intake of vitamin D3 may have a preventive effect against interstitial pneumonia.
The oxidative stresses are a major insult in pulmonary injury such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), two clinical manifestations of acute respiratory failure with substantially high morbidity and mortality. Mesenchymal stem cells (MSCs) hold a promise in treatments of many human diseases, mainly owing to their capacities of immunoregulation and antioxidative activity. The strong immunoregulatory role of human placental MSCs of fetal origin (hfPMSCs) has been previously demonstrated; their antioxidant activity, however, has yet been interrogated. In this report, we examined the antioxidative activity of hfPMSCs by accessing the ability to scavenge oxidants and radicals and to protect alveolar epithelial cells from antioxidative injury using both a cell coculture model and a conditioned culture medium (CM) of hfPMSCs. Results showed a comparable antioxidative capacity of the CM with 100 μ M of vitamin C (VC) in terms of the total antioxidant capacity (T-AOC), scavenging abilities of free radicals DPPH, hydroxyl radical (·OH), and superoxide anion radical (O 2⁻ ), as well as activities of antioxidant enzymes of SOD and GSH-PX. Importantly, both of the CM alone and cocultures of hfPMSCs displayed a protection of A549 alveolar epithelial cells from oxidative injury of 600 μ M hydrogen peroxide (H 2 O 2 ) exposure, as determined in monolayer and transwell coculture models, respectively. Mechanistically, hfPMSCs and their CM could significantly reduce the apoptotic cell fraction of alveolar epithelial A549 cells exposed to H 2 O 2 , accompanied with an increased expression of antiapoptotic proteins Bcl-2, Mcl-1, Nrf-2, and HO-1 and decreased proapoptotic proteins Bax, caspase 3, and Keap1, in comparison with naïve controls. Furthermore, hfPMSCs-CM (passage 3) collected from cultures exposed an inhibition of the Nrf2/Keap1/ARE signaling pathway which led to a significant reduction in caspase 3 expression in A549 cells, although the addition of Nrf2 inhibitor ML385 had no effect on the antioxidative activity of hfPMSCs-CM. These data clearly suggested that hfPMSCs protected the H 2 O 2 -induced cell oxidative injury at least in part by regulating the Nrf2-Keap1-ARE signaling-mediated cell apoptosis. Our study thus provided a new insight into the antioxidative mechanism and novel functions of hfPMSCs as antioxidants in disease treatments, which is warranted for further investigations.
A number of controlled trials have previously found that in some contexts, vitamin C can have beneficial effects on blood pressure, infections, bronchoconstriction, atrial fibrillation, and acute kidney injury. However, the practical significance of these effects is not clear. The purpose of this meta-analysis was to evaluate whether vitamin C has an effect on the practical outcomes: length of stay in the intensive care unit (ICU) and duration of mechanical ventilation. We identified 18 relevant controlled trials with a total of 2004 patients, 13 of which investigated patients undergoing elective cardiac surgery. We carried out the meta-analysis using the inverse variance, fixed effect options, using the ratio of means scale. In 12 trials with 1766 patients, vitamin C reduced the length of ICU stay on average by 7.8% (95% CI: 4.2% to 11.2%; p = 0.00003). In six trials, orally administered vitamin C in doses of 1–3 g/day (weighted mean 2.0 g/day) reduced the length of ICU stay by 8.6% (p = 0.003). In three trials in which patients needed mechanical ventilation for over 24 hours, vitamin C shortened the duration of mechanical ventilation by 18.2% (95% CI 7.7% to 27%; p = 0.001). Given the insignificant cost of vitamin C, even an 8% reduction in ICU stay is worth exploring. The effects of vitamin C on ICU patients should be investigated in more detail.
Background:
Vitamin D is a fundamental regulator of host defenses by activating genes related to innate and adaptive immunity. In this study, we analyzed the association among single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene, with clinical patterns of AIDS progression in antiretroviral treatment (ART)-naïve HIV-infected patients.
Methods:
We conducted a retrospective study in 667 HIV-infected patients, who were classified within three groups according to their AIDS progression pattern (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)). Five VDR SNPs (rs11568820, rs4516035, rs2228570, rs1544410, and rs7975232) were genotyped using Agena Bioscience's MassARRAY platform.
Results:
Significant association results were found for rs2228570. Within all HIV patients, the presence of T allele at VDR rs2228570 SNP was protective against AIDS progression (ordinal outcome) under additive (adjusted odds ratio (aOR) = 0.75; p = 0.009), dominant (aOR = 0.69; p = 0.015), and codominant (aOR = 0.56; p = 0.017) inheritance models. In addition, the same allele was protective under additive and codominant inheritance models when we compared with LTNPs vs. RPs [aOR = 0.64 (p = 0.019) and aOR = 0.37 (p = 0.018), respectively] and when we compared MPs vs. RPs [aOR = 0.72 (p = 0.035) and aOR = 0.45 (p = 0.028), respectively].
Conclusions:
The VDR rs2228570 T allele was related to a lower AIDS progression pattern in ART-naïve HIV-infected patients. These findings expand upon the knowledge about HIV pathogenesis in untreated HIV-infected patients with different clinical outcomes.
Background
Acute respiratory distress syndrome (ARDS), which is characterized by severe hypoxemia (PaO2/FIO2 ≤300 mmHg), is usually companied by uncontrolled inflammation, oxidative injury, and the damage to the alveolar-capillary barrier. Severe ARDS is usually companied with acute lung injury that worsen the patients’ condition. HIPK1 is a modulator of homeodomain-containing transcription factors and regulates multiple cellular biological process associated with inflammation and anti-stress responses.
Material/Methods
We used an LPS-induced mouse acute lung injury (ALI) model to investigate the possible role of HIPK1 in ALI pathophysiology.
Results
We found the HIPK1 was elevated in ALI model mice while interference of HIPK1 by siRNA attenuated the inflammation and oxidative stress indicators (H2O2, O⁻2, and NO). Further research found HIPK1 interference enhanced the autophagy.
Conclusions
Decreased HIPK1 in ALI showed protective effects in attenuating inflammation and oxidative stress and enhancing autophagy, indicating HIPK1 as a possible target in ALI management.
Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidant response element- (ARE-) driven cytoprotective protein expression. The activation of Nrf2 signaling plays an essential role in preventing cells and tissues from injury induced by oxidative stress. Under the unstressed conditions, natural inhibitor of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), traps Nrf2 in the cytoplasm and promotes the degradation of Nrf2 by the 26S proteasome. Nevertheless, stresses including highly oxidative microenvironments, impair the ability of Keap1 to target Nrf2 for ubiquitination and degradation, and induce newly synthesized Nrf2 to translocate to the nucleus to bind with ARE. Due to constant exposure to external environments, including diverse pollutants and other oxidants, the redox balance maintained by Nrf2 is fairly important to the airways. To date, researchers have discovered that Nrf2 deletion results in high susceptibility and severity of insults in various models of respiratory diseases, including bronchopulmonary dysplasia (BPD), respiratory infections, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and lung cancer. Conversely, Nrf2 activation confers protective effects on these lung disorders. In the present review, we summarize Nrf2 involvement in the pathogenesis of the above respiratory diseases that have been identified by experimental models and human studies and describe the protective effects of Nrf2 inducers on these diseases.
Two recent publications by Sheikh and Horner and Teng et al. reviewed studies on incorporating vitamin C to treat septic patients; however, a meta-analysis was not offered in either report. This commentary extends both reviews by integrating a meta-analysis and sharing aggregated results. Pooled analyses demonstrated a marked reduction in mortality and duration of vasopressor administration in the group with the use of vitamin C.
People living with human immunodeficiency virus (HIV) infection typically have hypovitaminosis D, which is linked to a large number of pathologies, including immune disorders and infectious diseases. Vitamin D (VitD) is a key regulator of host defense against infections by activating genes and pathways that enhance innate and adaptive immunity. VitD mediates its biological effects by binding to the Vitamin D receptor (VDR), and activating and regulating multiple cellular pathways. Single nucleotide polymorphisms in genes from those pathways have been associated with protection from HIV-1 infection. High levels of VitD and VDR expression are also associated with natural resistance to HIV-1 infection. Conversely, VitD deficiency is linked to more inflammation and immune activation, low peripheral blood CD4+ T-cells, faster progression of HIV disease, and shorter survival time in HIV-infected patients. VitD supplementation and restoration to normal values in HIV-infected patients may improve immunologic recovery during combination antiretroviral therapy, reduce levels of inflammation and immune activation, and increase immunity against pathogens. Additionally, VitD may protect against the development of immune reconstitution inflammatory syndrome events, pulmonary tuberculosis, and mortality among HIV-infected patients. In summary, this review suggests that VitD deficiency may contribute to the pathogenesis of HIV infection. Also, VitD supplementation seems to reverse some alterations of the immune system, supporting the use of VitD supplementation as prophylaxis, especially in individuals with more severe VitD deficiency.
Abstract Background Vitamin C is an essential water-soluble nutrient which cannot be synthesised or stored by humans. It is a potent antioxidant with anti-inflammatory and immune-supportive roles. Previous research has indicated that vitamin C levels are depleted in critically ill patients. In this study we have assessed plasma vitamin C concentrations in critically ill patients relative to infection status (septic shock or non-septic) and level of inflammation (C-reactive protein concentrations). Vitamin C status was also assessed relative to daily enteral and parenteral intakes to determine if standard intensive care unit (ICU) nutritional support is adequate to meet the vitamin C needs of critically ill patients. Methods Forty-four critically ill patients (24 with septic shock, 17 non-septic, 3 uncategorised) were recruited from the Christchurch Hospital Intensive Care Unit. We measured concentrations of plasma vitamin C and a pro-inflammatory biomarker (C-reactive protein) daily over 4 days and calculated patients’ daily vitamin C intake from the enteral or total parenteral nutrition they received. We compared plasma vitamin C and C-reactive protein concentrations between septic shock and non-septic patients over 4 days using a mixed effects statistical model, and we compared the vitamin C status of the critically ill patients with known vitamin C bioavailability data using a four-parameter log-logistic response model. Results Overall, the critically ill patients exhibited hypovitaminosis C (i.e.
Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100–200 mg/day), which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. ALI and ARDS result are associated with high mortality in patients. At present, no effective treatments for ALI and ARDS exist. It is established that vitamin D exhibits anti‑inflammatory effects, however, the specific effect of vitamin D on ALI remains largely unknown. The aim of the present study was to investigate whether, and by which mechanism, vitamin D alleviates lipopolysaccharide (LPS)‑induced ALI. The results demonstrated that a vitamin D agonist, calcitriol, exhibited a beneficial effect on LPS‑induced ALI in rats; calcitriol pretreatment significantly improved LPS‑induced lung permeability, as determined using Evans blue dye. Results from reverse transcription‑quantitative polymerase chain reaction, western blotting and ELISA analysis demonstrated that calcitriol also modulated the expression of members of the renin‑angiotensin system (RAS), including angiotensin (Ang) I‑converting enzymes (ACE and ACE2), renin and Ang II, which indicates that calcitriol may exert protective effects on LPS‑induced lung injury, at least partially, by regulating the balance between the expression of members of the RAS. The results of the present study may provide novel targets for the future treatment of ALI.
We report a case of virus-induced acute respiratory distress syndrome (ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS, resulting from enterovirus/rhinovirus respiratory infection. From very significant preclinical research performed at Virginia Commonwealth University with vitamin C and with the very positive results of a previously performed phase I safety trial infusing high dose vitamin C intravenously into patients with severe sepsis, we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic. We report here the case of a 20-year-old, previously healthy, female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS. She contracted the infection in central Italy while on an 8-d spring break from college. During a return flight to the United States, she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS. When support with mechanical ventilation failed, extracorporeal membrane oxygenation (ECMO) was initiated. Twelve hours following ECMO initiation, high dose intravenous vitamin C was begun. The patient’s recovery was rapid. ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae. Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae. Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes.
HKU1 is a human betacoronavirus that causes mild yet prevalent respiratory disease, and is related to the zoonotic SARS and MERS betacoronaviruses, which have high fatality rates and pandemic potential. Cell tropism and host range is determined in part by the coronavirus spike (S) protein, which binds cellular receptors and mediates membrane fusion. As the largest known class I fusion protein, its size and extensive glycosylation have hindered structural studies of the full ectodomain, thus preventing a molecular understanding of its function and limiting development of effective interventions. Here we present the 4.0 Å resolution structure of the trimeric HKU1 S protein determined using single-particle cryo-electron microscopy. In the pre-fusion conformation, the receptor-binding subunits, S1, rest above the fusion-mediating subunits, S2, preventing their conformational rearrangement. Surprisingly, the S1 C-terminal domains are interdigitated and form extensive quaternary interactions that occlude surfaces known in other coronaviruses to bind protein receptors. These features, along with the location of the two protease sites known to be important for coronavirus entry, provide a structural basis to support a model of membrane fusion mediated by progressive S protein destabilization through receptor binding and proteolytic cleavage. These studies should also serve as a foundation for the structure-based design of betacoronavirus vaccine immunogens.
Background: Vitamin C (ascorbate) is likely to be essential for skeletal muscle structure and function via its role as an enzyme cofactor for collagen and carnitine biosynthesis. Vitamin C may also protect these metabolically active cells from oxidative stress.
Objective: We investigated the bioavailability of vitamin C to human skeletal muscle in relation to dietary intake and plasma concentrations and compared this relation with ascorbate uptake by leukocytes.
Design: Thirty-six nonsmoking men were randomly assigned to receive 6 wk of 0.5 or 2 kiwifruit/d, an outstanding dietary source of vitamin C. Fasting blood samples were drawn weekly, and 24-h urine and leukocyte samples were collected before intervention, after intervention, and after washout. Needle biopsies of skeletal muscle (vastus lateralis) were carried out before and after intervention.
Results: Baseline vastus lateralis ascorbate concentrations were ∼16 nmol/g tissue. After intervention with 0.5 or 2 kiwifruit/d, these concentrations increased ∼3.5-fold to 53 and 61 nmol/g, respectively. There was no significant difference between the responses of the 2 groups. Mononuclear cell and neutrophil ascorbate concentrations increased only ∼1.5- and ∼2-fold, respectively. Muscle ascorbate concentrations were highly correlated (P < 0.001) with dietary intake (R = 0.61) and plasma concentrations (R = 0.75) in the range from 5 to 80 μmol/L.
Conclusions: Human skeletal muscle is highly responsive to vitamin C intake and plasma concentrations and exhibits a greater relative uptake of ascorbate than leukocytes. Thus, muscle appears to comprise a relatively labile pool of ascorbate and is likely to be prone to ascorbate depletion with inadequate dietary intake. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12611000162910.
Ascorbate can act as both a reducing and oxidising agent in vitro depending on its environment. It can modulate the intracellular redox environment of cells and therefore is predicted to modulate thiol-dependent cell signalling and gene expression pathways. Using proteomic analysis of vitamin C-treated T cells in vitro, we have previously reported changes in expression of five functional protein groups associated with signalling, carbohydrate metabolism, apoptosis, transcription and immune function. The increased expression of the signalling molecule phosphatidylinositol transfer protein (PITP) was also confirmed using Western blotting. Herein, we have compared protein changes elicited by ascorbate in vitro, with the effect of ascorbate on plasma potassium levels, on peripheral blood mononuclear cell (PBMC) apoptosis and PITP expression, in patients supplemented with vitamin C (0-2 g/d) for up to 10 weeks to investigate whether in vitro model systems are predictive of in vivo effects. PITP varied in expression widely between subjects at all time-points analysed but was increased by supplementation with 2 g ascorbate/d after 5 and 10 weeks. No effects on plasma potassium levels were observed in supplemented subjects despite a reduction of K+ channel proteins in ascorbate-treated T cells in vitro. Similarly, no effect of vitamin C supplementation on PBMC apoptosis was observed, whilst ascorbate decreased expression of caspase 3 recruitment domain protein in vitro. These data provide one of the first demonstrations that proteomics may be valuable in developing predictive markers of nutrient effects in vivo and may identify novel pathways for studying mechanisms of action in vivo.
An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in the city of Wuhan in China and has widely spread worldwide. Currently, it is vital to explore potential intermediate hosts of SARS-CoV-2 to control COVID-19 spread. Therefore, we reinvestigated published data from pangolin lung samples from which SARS-CoV-like CoVs were detected by Liu et al. [1]. We found genomic and evolutionary evidence of the occurrence of a SARS-CoV-2-like CoV (named Pangolin-CoV) in dead Malayan pangolins. Pangolin-CoV is 91.02% and 90.55% identical to SARS-CoV-2 and BatCoV RaTG13, respectively, at the whole-genome level. Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. Five key amino acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and SARS-CoV-2, but four amino acid mutations are present in RaTG13. Both Pangolin-CoV and RaTG13 lost the putative furin recognition sequence motif at S1/S2 cleavage site that can be observed in the SARS-CoV-2. Conclusively, this study suggests that pangolin species are a natural reservoir of SARS-CoV-2-like CoVs.
Background
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.
Methods
In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.
Findings
191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/L (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days.
Interpretation
The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/L could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Funding
Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
Introduction
The Republic of Korea (ROK) military has a high incidence of respiratory diseases at training centres. Vitamin C has been reported to reduce the incidence of colds. For the purpose of preventing soldiers' respiratory diseases, this study aimed to investigate whether vitamin C intake can prevent common colds in the ROK Army soldiers.
Methods
This was a randomised, placebo-controlled, and double-blind trial of soldiers who enlisted in the Korea Army Training Centre for 30 days from 12 February to 13 March 2018. The study participants were divided into groups (vitamin C vs placebo). The military medical records were searched to determine whether the participants had a common cold. Multiple logistic regression analysis was performed to identify the association between vitamin C intake and diagnosis of common colds. In addition, subgroup analysis on the relationship between vitamin C intake and common cold according to smoking status, training camp and physical rank was conducted.
Results
A total of 1444 participants were included in our study. Of these participants, 695 received vitamin C (6000 mg/day, vitamin C group), while 749 participants received placebo (0 mg/day, placebo group). The vitamin C group had a 0.80-fold lower risk of getting a common cold than did the placebo group. Subgroup analyses showed that this effect was stronger among subjects in camp A, among never smokers and among those in physical rank 3.
Conclusion
Vitamin C intake provides evidence to suggest that reducing the common colds in Korean Army soldiers. Our results may serve as a basis for introducing military healthcare policies that can provide vitamin C supplementation for military personnel in basic military training.
Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease.
Background:
Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection.
Methods:
Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation.
Findings:
All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8-9 and a 5-min Apgar score of 9-10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus.
Interpretation:
The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy.
Funding:
Hubei Science and Technology Plan, Wuhan University Medical Development Plan.
Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.
Background:
In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed.
Methods:
We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus.
Findings:
The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues.
Interpretation:
2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation.
Funding:
National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
Background:
In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia.
Methods:
In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020.
Findings:
Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure.
Interpretation:
The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection.
Funding:
National Key R&D Program of China.
The pleiotropic role of vitamin D has been explored over the past decades and there is compelling evidence for an epidemiological association between poor vitamin D status and a variety of diseases. While the potential anti‐viral effect of vitamin D has recently been described, the underlying mechanisms by which vitamin D deficiency could contribute to viral disease development remain poorly understood. The possible interactions between viral infections and vitamin D appear to be more complex than previously thought. Recent findings indicate a complex interplay between viral infections and vitamin D, including the induction of anti‐viral state, functional immunoregulatory features, interaction with cellular and viral factors, induction of autophagy and apoptosis, and genetic and epigenetic alterations. While crosstalk between vitamin D and intracellular signalling pathways may provide an essential modulatory effect on viral gene transcription, the immunomodulatory effect of vitamin D on viral infections appears to be transient. The interplay between viral infections and vitamin D remains an intriguing concept, and the global imprint that vitamin D can have on the immune signature in the context of viral infections is an area of growing interest.
SNP in the vitamin D receptor ( VDR ) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes ( DBP , DHCR7 , RXRA , CYP2R1 , CYP27B1 , CYP24A1 , CYP3A4 , CYP27A1 , LRP2 , CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, Pfor trend ≤0·030). This association was replicated for rs4334089 in the validation cohort ( Pfor trend =0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.
The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Pre-clinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase healthspan and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.
Background:
The global burden of sepsis is estimated as 15 to 19 million cases annually with a mortality rate approaching 60% in low income countries.
Methods:
In this retrospective before-after clinical study, we compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone and thiamine during a 7-month period (treatment group) compared to a control group treated in our ICU during the preceding 7 months. The primary outcome was hospital survival. A propensity score was generated to adjust the primary outcome.
Findings:
There were 47 patients in both treatment and control groups with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared to 40.4% (19 of 47) in the control group (p < 0.001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI 0.04-0.48, p=002). The SOFA score decreased in all patients in the treatment group with none developing progressive organ failure. Vasopressors were weaned off all patients in the treatment group, a mean of 18.3 ± 9.8 hours after starting treatment with vitamin C protocol. The mean duration of vasopressor use was 54.9 ± 28.4 hours in the control group (p<0.001).
Conclusion:
Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine may prove to be effective in preventing progressive organ dysfunction including acute kidney injury and reducing the mortality of patients with severe sepsis and septic shock. Additional studies are required to confirm these preliminary findings.
Exposure of cells to sublethal oxidative stress results in the modulation of various signaling pathways. Oxidants can activate and inactivate transcription factors, membrane channels, and metabolic enzymes, and regulate calcium-dependent and phosphorylation signaling pathways. Oxidation and reduction of thiol proteins are thought to be the major mechanisms by which reactive oxidants integrate into cellular signal transduction pathways. This review focuses on mechanisms for sensing and transmitting redox signals, from the perspective of their chemical reactivity with specific oxidants. We discuss substrate preferences for different oxidants and how the kinetics of these reactions determines how each oxidant will react in a cell. This kinetic approach helps to identify initial oxidant-sensitive targets and elucidate mechanisms involved in transmission of redox signals. It indicates that only those proteins with very high reactivity, such as peroxiredoxins, are likely to be direct targets for hydrogen peroxide. Other more modestly reactive thiol proteins such as protein tyrosine phosphatases are more likely to become oxidized by an indirect mechanism. The review also examines oxidative changes observed during receptor-mediated signaling, the strengths and limitations of detection methods for reactive oxidant production, and the evidence for hydrogen peroxide acting as the second messenger. We discuss areas where observations in cell systems can be rationalized with the reactivity of specific oxidants and where further work is needed to understand the mechanisms involved.
Humans acquire vitamin C (ascorbate) from their diet, and optimal tissue concentrations are required to maintain its enzyme cofactor and antioxidant activities. How dietary intake affects tissue concentrations is difficult to monitor and has generally been based on the measurement of plasma concentrations.
We aimed to determine the effect of various ascorbate intakes on tissue concentrations in the Gulo mouse model of vitamin C deficiency and to compare the effectiveness of delivery when ascorbate was added to the drinking water or obtained through a fruit source (kiwifruit).
Gulo(-/-) mice were fed various amounts of ascorbate for 1 mo, either in their drinking water or as a kiwifruit gel. Tissue vitamin C content was measured and compared with concentrations in wild-type mice.
Ascorbate concentrations in serum, liver, kidney, heart, and white blood cells were extremely labile and were well below concentrations observed in the wild-type mice when serum concentrations were below saturation. All tissues except for brain were rapidly depleted when intake was stopped. Consumption of a preparation of fresh kiwifruit (either green or gold varieties) resulted in up to 5 times more effective delivery to tissues than when ascorbate was administered via the drinking water.
Subsaturation concentrations of plasma ascorbate resulted in severe deficiency in many tissues, and saturating amounts were required to achieve tissue concentrations similar to those found in wild-type animals. It is possible that the bioavailability of ascorbate is superior from some foods, such as kiwifruit. These results have important implications for human nutrition.