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Reply: “Vitamin D Supplementation in Influenza and COVID-19 Infections. Comment on: Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Nutrients 2020, 12(4), 988”

MDPI
Nutrients
Authors:
  • Sunlight, Nutrition and Health Research Center
  • GrassrootsHealth
nutrients
Reply
Reply: “Vitamin D Supplementation in Influenza and
COVID-19 Infections. Comment on: Evidence That
Vitamin D Supplementation Could Reduce Risk of
Influenza and COVID-19 Infections and Deaths
Nutrients 2020, 12(4), 988”
William B. Grant 1,* , Carole A. Baggerly 2and Henry Lahore 3
1Sunlight, Nutrition, and Health Research Center, P.O. Box 641603, San Francisco, CA 94164-1603, USA
2GrassrootsHealth, Encinitas, CA 95101, USA; carole@grassrootshealth.org
32289 Highland Loop, Port Townsend, WA 98368, USA; hlahore@gmail.com
*Correspondence: wbgrant@infionline.net; Tel.: +1-415-409-1980
Received: 20 April 2020; Accepted: 8 May 2020; Published: 1 June 2020


Keywords:
African Americans; COVID-19; C-reactive protein; hemoglobin; influenza; randomized
controlled trials; respiratory tract infections; vitamin D; vitamin D2; vitamin D3
We thank Dr. Hasan for the comments [
1
] on our review [
2
] and for providing us the opportunity to
extend the discussion regarding the role of vitamin D in reducing the risk of respiratory tract infections.
Dr. Hasan’s first point: “However, we are rather concerned with authors’ recommendation that
people at risk of COVID-19 should consider ‘taking 10,000 IU/d of vitamin D
3
for a few weeks to
rapidly raise 25(OH)D concentrations, followed by 5000 IU/d to reduce the risk of infection’. We believe
that authors’ recommendation of using a high dose of vitamin D supplementation is inappropriate
as there is no robust clinical evidence to support such claims.” Our recommendation was based on
reaching a serum 25-hydroxyvitamin D [25(OH)D] concentration between 40 and 60 ng/mL in advance
of the winter viral respiratory tract infection (RTI) season. According to Figure 1 in an article by
Heaney [
3
], when starting at a level of around 20 ng/mL it takes about 35 days to reach 60 ng/mL
with 10,000 IU/d and 85 days with 4000 IU/d. A randomized controlled trial (RCT) published in 2015
showed that after a single dose of 250,000 IU of vitamin D
3
given to healthy volunteers between the
ages of 18 and 65 years with baseline serum levels of <17 ng/m, serum 25(OH)D concentrations at five
days increased to an average of 41 ng/mL [
4
]. There were no adverse eects. However, after 90 days,
25(OH)D concentrations were back to near baseline values. In the preprint of the first submitted
version of our review [
5
], we discussed the results of reported influenza-like illness (ILI) with respect to
serum 25(OH)D concentrations for GrassrootsHealth participants (this information was omitted from
the published review since it should go through the peer review process independent of its inclusion in
a review.) Table 1 reports that, compared to [25(OH)D] of <20 ng/mL, the adjusted odds ratio for ILI for
40–49 ng/mL, 50–59 ng/mL, and
60 ng/mL were 0.04, 0.02, and 0.03, respectively. While this finding
was not related to COVID-19, there are indications that viral RTIs have similar etiologies. Those who
are concerned about exposure to the COVID-19 virus or who have symptoms of COVID-19 infection
might benefit from a much larger dose, although clinical trials need to be performed.
Very recently, a preprint reported severity of COVID-19 infections with respect to 25(OH)D
concentration in three Asian countries [
6
]. Out of 49 patients with mild symptoms, 47 had serum
25(OH)D concentrations of >30 ng/mL compared with only four of 59 with ordinary symptoms, two of
56 severe patients, and two of 48 critical patients. The mean serum 25(OH)D concentrations for mild,
ordinary, severe, and critical patients were 31, 27, 21, and 17 ng/mL, respectively.
Nutrients 2020,12, 1620; doi:10.3390/nu12061620 www.mdpi.com/journal/nutrients
Nutrients 2020,12, 1620 2 of 5
Results of a study of seroprevalence for COVID-19 in Santa Clara County, California were reported
in a preprint [
7
], with A total of 3330 people included; 50 people were found to have antibodies for
COVID-19. After adjusting the data to correspond to the demographic characteristics of the county,
the seroprevalence to COVID-19 was estimated at between 2.49% and 4.16%, with uncertainty bounds
ranging from 1.80% up to 5.70%. This estimate translates to 48,000 to 81,000 people in the county,
which is 50 to 80 times the 956 people that were identified by April 1, 2020. It should be noted that this
study has not been peer reviewed and may have some methodological issues to address. We think
it likely that many have contracted COVID-19 with minimal or no symptoms. Supporting this idea,
several coronaviruses exist that result in minor colds in the January–February timeframe, as found
from a study of children crossing the Southern China–Hong Kong border [8].
These two studies support our suggestion of 40 to 60 ng/mL, since one study presented COVID-19
infection with 25(OH)D concentrations of >30 ng/mL and the other found that many people were
infected without symptoms. Elderly people with chronic diseases are very likely to have low 25(OH)D
concentrations, as discussed in our review [
2
]. However, further studies are required to better determine
the threshold for protection against COVID-19 infection with symptoms.
As is well known, COVID-19 patients in critical condition often require a ventilator to help supply
oxygen to their blood. A meta-analysis of laboratory findings of clinical characteristics for COVID-19
patients found that the pooled frequency of anemia from two studies was 44% (95% CI, 30%–58%),
while the pooled frequency for high C-reactive protein (CRP) from eight studies was 72% (95% CI,
54%–85%) [
9
]. A study conducted in Egypt found that serum 25(OH)D concentration was inversely
correlated with the degree of severity of acute lower RTIs (r=0.80) in hospitalized infants with a
mean age of 11
±
3 months [
10
]. In addition, hemoglobin level was also highly correlated with serum
25(OH)D concentration (r=0.71), with the mean concentration ranging from 9 ng/dL for 6 ng/mL
25(OH)D to 14 ng/dL for 50 ng/mL 25(OH)D.
While low-dose vitamin D supplementation was not found to increase hemoglobin concentration
in short-term studies [
11
], high-dose vitamin D supplementation was. A clinical trial involving
30 mechanically ventilated, critically ill adults were assigned to three groups to receive a placebo,
250,000 IU vitamin D
3
, or 500,000 IU vitamin D
3
total during a five-day periods [
12
]. Mean baseline
hemoglobin concentration was between 8.5 and 10.5 g/dL for the three groups. Hemoglobin concentration
increased significantly only for the 500,000 IU vitamin D
3
group, who experienced a 2 g/dL increase in four
weeks. However, a phase 3 RCT involving 1078 critically ill vitamin D-deficient patients, with those in the
treatment arm given 540,000 IU vitamin D
3
supplementation within 12 h of admission to an intensive care
unit, found no significant benefit in terms of 90-day mortality rate (P=0.26) or with respect to secondary
clinical, physiological, or safety end-points [13].
A cross-sectional study using data from the USA’s National Health and Nutrition Examination
Surveys data found that CRP varied from 222 (95% CI, 205–241) mcg/dL for a 25(OH)D concentration
of <12 ng/mL to 199 (179–201) mcg/dL for >30 ng/mL 25(OH)D [14].
Thus, by analogy, vitamin D deficiency appears to be a very important risk factor for severe
COVID-19 infection.
Dr. Hasan’s second point: “The authors have conveniently ignored the results of some key clinical
studies evaluating the eectiveness of vitamin D supplementation in reducing the risk of developing
respiratory tract infections (RTIs).” The meta-analysis of 15 RCTs on the eectiveness of vitamin D
supplementation on risk of RTIs by Gysin et al. [
15
] had a serious flaw: the evaluations were made
based on vitamin D dose vs. placebo, not serum 25(OH)D concentration. Vitamin D does not have a
direct bearing on disease risk; it is 25(OH)D concentration that was found to be associated with disease
risk. Inspection of the RCTs used in their analysis in Figure 3 presented some with very low baselines
with significantly reduced risk of RTIs and very low vitamin D doses, while others with high baseline
25(OH)D concentrations and high vitamin D doses exhibited no eect. Heaney’s guidelines for RCTs
for nutrients such as vitamin D were discussed in our review [
16
], the most important factor being that
Nutrients 2020,12, 1620 3 of 5
they be based on 25(OH)D concentration, both baseline and achieved, and that sucient vitamin D
3
be given.
Regarding the individual participant data meta-analysis of RTI in vitamin D RCTs [
17
], there were
few participants who achieved a 25(OH)D concentration of >40 ng/mL, so they could not adequately
assess the impact of high 25(OH)D concentration. We noted that a study in Connecticut found 38 ng/mL
as the threshold for a significantly lower risk of community-based pneumonia [18].
Dr. Hasan’s third point: “Although high dose vitamin D3 was not found to increase the risk
of kidney stone or hypercalcemia, it is not devoid of side eects as a randomized clinical trial only
observed significant lower radial bone and tibial bone mineral density with 3-year-treatment of
vitamin D at a dose of 10,000 IU/d”. Regarding the possible adverse eects of high-dose vitamin D
supplementation, we read the article by Burt et al. [
19
]. As mentioned in the comment, the only adverse
finding was a reduction (3.5%) in bone mass density. However, bone mass density does not equate to
bone strength, and the reductions in strength measured as failure load were not significant. That was a
three-year study, whereas we are suggesting a strategy for the winter RTI season. We also note that all
pharmaceutical drugs have adverse side eects. If high-dose vitamin D is considered a drug, it diers
from pharmaceutical drugs in that it has many side benefits [20].
Dr. Hasan’s fourth point: “Given the possible negative impact on bone mineral density with
high dose vitamin D3, it is probably wise to wait for the results of ongoing clinical trials that are
registered to explore the relationship between vitamin D and COVID-19.” We agree that RCTs should be
conducted to evaluate the role of vitamin D in preventing and treating COVID-19 infection. However,
we strongly disagree that vitamin D supplementation should be held in abeyance for prevention until
such RCTs are completed and reported. Those at highest risk of infection due to having chronic disease,
low 25(OH)D status, and/or being in frequent contact with others likely to be infected should be taking
vitamin D. As noted, there is mounting evidence that vitamin D can reduce the risk and severity
of RTIs, including that the mechanisms are known, that there are many health benefits of higher
25(OH)D concentrations, and that there are very few adverse eects of vitamin D
3
supplementation.
Vitamin D has demonstrated eectiveness in reducing the risk of overall cancer incidence and death,
as well as the risk of progressing from pre-diabetes to diabetes in secondary results of major vitamin
D RCTs [
21
]. Thus, there is much to gain and little to lose by taking vitamin D supplements now for
COVID-19 prevention. RCTs should be conducted for treatment to explore at which stages of infection
what baseline 25(OH)D concentrations, vitamin D doses, and achieved 25(OH)D concentrations are
associated with benefits and adverse eects, if any.
Dr. Hasan’s fifth point questioned our statement: “A clinical trial involving postmenopausal
women living on Long Island, NY with mean baseline 25(OH)D concentration 19
±
8 ng/mL found
that supplementation with 2000 IU/d resulted in significantly fewer upper respiratory tract infections,
including influenza, than a placebo or supplementation with 800 IU/d [
22
].” In this trial, 104 participants
took a placebo for three years and suered from 29 RTIs in total, 104 took 800 IU/d vitamin D
3
for two
years and suered 8 RTIs, and 104 took 2000 IU/d vitamin D
3
and one RTI was recorded. The odds
ratio for 800 IU/d vs. placebo was 0.39 (95% confidence interval, 0.17–0.87, P=0.02), while that for
2000 IU/d vs. placebo was 0.09 (0.01–0.50, P=0.02).
We use this opportunity to respond to two important comments by other readers of our review.
One questioned why we did not indicate that vitamin D
3
(cholecalciferol) be used rather than
vitamin D
2
(ergocalciferol), the answer being that, in some countries, the only high-dose vitamin D
is ergocalciferol. However, cholecalciferol is a better choice, in part since it is the type of vitamin D
produced in the skin through ultraviolet B irradiation of 7-dehydrocholesterol followed by a thermal
reaction. After publication of our review, an article was published reporting the eects of vitamin D on
gene expression of rat oligodendrocyte precursor cells. The study found that vitamin D
3
influenced
1272 genes in 24 h compared to only 574 for vitamin D [
23
]. Most of the eects of vitamin D are through
the hormonal metabolite 1,25-dihydroxyvitamin D, which activates vitamin D receptors bound to
chromosomes, thereby aecting the expression of many genes.
Nutrients 2020,12, 1620 4 of 5
The second question was why we did not point out that African Americans (AAs) have a much
higher risk of COVID-19 infection and death than white Americans. At the time we submitted our
manuscript, the data comparing AA COVID-19 infection and mortality rates were not available.
In addition, there are a number of other reasons why AAs have higher COVID-19 rates, including that
they have higher chronic disease rates than white Americans [24].
People with chronic diseases generally have low 25(OH)D concentrations (see Table 2 in [
2
]).
Now, however, it is well-known that AAs have much higher COVID-19 infection and mortality
rates [
25
]. Based on the National Health and Nutrition Examination Survey (NHANES) 2001–2010,
the prevalence of serum 25(OH)D concentrations <20 ng/mL was 72% for non-Hispanic blacks (NHBs),
43% for Hispanics, and 19% for non-Hispanic whites, with the prevalence of <10 ng/mL being 17%
in NHBs [
26
]. Of all the risk factors AAs have for becoming infected with COVID-19, raising serum
25(OH)D concentrations is the easiest one to counter.
Funding: No funding was received for this study.
Conflicts of Interest:
W.B.G. receives funding from Bio-Tech Pharmacal, Inc. (Fayetteville, AR). GrassrootsHealth
works with various supplement suppliers to test the ecacy of their products in various custom projects.
These suppliers may be listed as ’Sponsors’ of GrassrootsHealth. H.L. has no conflicts of interest to declare.
VitaminDWiki.com receives funding from Bio-Tech Pharmacal, Inc.
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©
2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
... Many epidemiological studies found an inversely proportional connection between vitamin D deficiency and COVID-19 severity and outcomes. Lower level of vitamin D is believed to be associated with greater risk of developing complications like ARDS, heart failure, and sepsis which are main cause of deaths in COVID-19 [25]. Many researchers like H.K. Biesalski [26] and E. Laird et al. [27] also advocated strong relationship between vitamin D deficiency and the severity of COVID-19 disease. ...
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... 13,14 Recent studies have explored the potential association between vitamin D status and the risk of COVID-19 infection and its outcomes. [15][16][17][18] It has been proposed that vitamin D deficiency may be linked to an increased risk of COVID-19 infection and poorer outcomes in infected individuals. [19][20][21] Given the high prevalence of vitamin D deficiency in hemodialysis patients and the potential role of vitamin D in modulating immune responses, it is critical to investigate the association between vitamin D levels and COVID-19 infection risk and outcomes in this vulnerable population. ...
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... Zhang and Liu (2020) suggested that vitamin D can protect from diseases relevant to immune deficiency and is also involved in regulating immune cells. Likewise, Grant and Baggerly (2020) proposed that higher doses of vitamin D help treat viral diseases. Ilie et al. (2020) observed a negative correlation between levels of mean vitamin D and the number of cases of COVID-19related mortality. ...
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The COVID-19 pandemic has sparked a paradigm change in pandemic preparedness measures, motivating an investigation of non-pharmaceutical therapies. This research dives into the lessons learned from COVID-19 to strengthen our strategy to prevent future pandemics. The study aimed to extract valuable insights from the COVID-19 experience, extrapolating lessons learned to develop strong strategies that include diet, lifestyle, risk factors and non-pharmaceutical treatments. Nutrition and lifestyle influences on illness susceptibility were studied using a comprehensive examination of scholarly literature, reports and epidemiological studies. Role of essential risk variables was investigated in magnifying pandemic outcomes and the efficiency of non-pharmaceutical treatments in reducing infectious agent transmission. The analysis demonstrates the long-term utility of COVID-19 findings. This review emphasizes the importance of nutrition and lifestyle variables in determining susceptibility to infectious illnesses. Furthermore, a detailed examination of risk variables shows critical predictors of pandemic severity. Most significantly, the findings highlight the effectiveness of non-pharmaceutical measures, emphasizing their vital role in pandemic containment. This study has far-reaching ramifications that advocate for a paradigm change towards comprehensive pandemic preparation using the lessons learned during COVID-19. Research findings highlight the need for a multifaceted strategy, including diet, lifestyle changes, targeted risk reduction and non-pharmaceutical therapies. This study provides a road map for improving global resilience to potential future pandemics, calling for preventative strategies beyond pharmacological remedies.
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Background Electronic health records (EHRs) facilitate the accessibility and sharing of patient data among various health care providers, contributing to more coordinated and efficient care. Objective This study aimed to summarize the evolution of secondary use of EHRs and their interoperability in medical research over the past 25 years. Methods We conducted an extensive literature search in the PubMed, Scopus, and Web of Science databases using the keywords Electronic health record and Electronic medical record in the title or abstract and Medical research in all fields from 2000 to 2024. Specific terms were applied to different time periods. Results The review yielded 2212 studies, all of which were then screened and processed in a structured manner. Of these 2212 studies, 2102 (93.03%) were included in the review analysis, of which 1079 (51.33%) studies were from 2000 to 2009, 582 (27.69%) were from 2010 to 2019, 251 (11.94%) were from 2020 to 2023, and 190 (9.04%) were from 2024. Conclusions The evolution of EHRs marks an important milestone in health care’s journey toward integrating technology and medicine. From early documentation practices to the sophisticated use of artificial intelligence and big data analytics today, EHRs have become central to improving patient care, enhancing public health surveillance, and advancing medical research.
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Background Our study aimed to describe the group of severe COVID-19 patients at an institutional level, and determine factors associated with different outcomes. Methods A retrospective chart review of patients admitted with severe acute hypoxic respiratory failure due to COVID-19 infection. Based on outcomes, we categorized 3 groups of severe COVID-19: (1) Favorable outcome: progressive care unit admission and discharge (2) Intermediate outcome: ICU care (3) Poor outcome: in-hospital mortality. Results Eighty-nine patients met our inclusion criteria; 42.7% were female. The average age was 59.7 (standard deviation (SD):13.7). Most of the population were Caucasian (95.5%) and non-Hispanic (91.0%). Age, sex, race, and ethnicity were similar between outcome groups. Medicare and Medicaid patients accounted for 62.9%. The average BMI was 33.5 (SD:8.2). Moderate comorbidity was observed, with an average Charlson Comorbidity index (CCI) of 3.8 (SD:2.6). There were no differences in the average CCI between groups(p = 0.291). Many patients (67.4%) had hypertension, diabetes (42.7%) and chronic lung disease (32.6%). A statistical difference was found when chronic lung disease was evaluated; p = 0.002. The prevalence of chronic lung disease was 19.6%, 27.8%, and 40% in the favorable, intermediate, and poor outcome groups, respectively. Smoking history was associated with poor outcomes (p = 0.04). Only 7.9% were fully vaccinated. Almost half (46.1%) were intubated and mechanically ventilated. Patients spent an average of 12.1 days ventilated (SD:8.5), with an average of 6.0 days from admission to ventilation (SD:5.1). The intermediate group had a shorter average interval from admission to ventilator (77.2 hours, SD:67.6), than the poor group (212.8 hours, SD:126.8); (p = 0.001). The presence of bacterial pneumonia was greatest in the intermediate group (72.2%), compared to the favorable group (17.4%), and the poor group (56%); this was significant (p<0.0001). In-hospital mortality was seen in 28.1%. Conclusion Most patients were male, obese, had moderate-level comorbidity, a history of tobacco abuse, and government-funded insurance. Nearly 50% required mechanical ventilation, and about 28% died during hospitalization. Bacterial pneumonia was most prevalent in intubated groups. Patients who were intubated with a good outcome were intubated earlier during their hospital course, with an average difference of 135.6 hours. A history of cigarette smoking and chronic lung disease were associated with poor outcomes.
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The associations of vitamin D receptor (VDR)- single nucleotide polymorphisms (SNPs) with the symptoms of COVID-19 may vary between patients with different severities of COVID-19. Therefore, in the present study, we aim to compare VDR polymorphisms in severe and mild COVID-19 patients. In this study, a total number of 85 hospitalized patients and 91 mild/moderate patients with COVID-19 were recruited. SNPs in VDR genes were determined using ARMS and then confirmed by sanger sequencing. The mean (SD) age of participants in hospitalized and non-hospitalized group was 59.0 (12.4) and 47.8 (14.8) years, respectively. Almost 46% of participants in hospitalized and 48% of participant in non-hospitalized group were male. The frequency of TT genotype of SNP rs11568820 was significantly lower in hospitalized than non-hospitalized group (3.5% vs. 17.6%; P = 0.018). However, there was no significant differences between genotypes of SNPs rs7970314 and rs4334089 and also alleles frequencies in all SNPs of two groups. The genotype of rs11568820 SNP had an inverse association with hospitalization of patients with COVID-19 after adjustment for comorbidities [OR 0.18, 95% CI 0.04, 0.88; P = 0.034]. While, there was no relationship between genotypes of SNPs rs7970314 and rs4334089 and hospitalization. The TT genotype of rs11568820 plays protective role in sever COVID-19 and hospitalization. Further studies with a large sample size which consider various confounding factors are warranted to confirm our results.
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SARS‐CoV‐2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus–host protein–protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia (‘cytokine storm’), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25–70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new ‘onset’ clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.
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Background This review analyzed the magnitude of the COVID-19 pandemic globally and in India and the measures to counter its effect using natural and innate immune booster molecules. The study focuses on two phases: the first focuses on the magnitude, and the second on the effect of antioxidants (natural compounds) on SARS-CoV-2. Methods The magnitude of the prevalence, mortality, and comorbidities was acquired from the World Health Organization (WHO) report, media, a report from the Ministry of Health and Family Welfare (MoHFW), newspapers, and the National Centre of Disease Control (NCDC). Research articles from PubMed as well as other sites/journals and databases were accessed to gather literature on the effect of antioxidants. Results In the elderly and any chronic diseases, the declined level of antioxidant molecules enhanced the reactive oxygen species, which in turn deprived the immune system. Conclusion Innate antioxidant proteins like sirtuin and sestrin play a vital role in enhancing immunity. Herbal products and holistic approaches can also be alternative solutions for everyday life to boost the immune system by improving the redox balance in COVID-19 attack. This review analyzed the counteractive effect of alternative therapy to boost the immune system against the magnitude of the COVID-19 pandemic.
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Objective: In this study, we examined changes in purchase behavior of alcoholic beverages (ie, soju, beer, wine, traditional Korean liquor, and liquor) and non-alcoholic beverages (ie, fruit and vegetable juices, coffee, tea, bottled water, milk, yogurt, and plant-based milk) before and after the COVID-19 pandemic. Methods: Monthly beverage expenditure data, based on Korean household demographic information, was used for 3 years and 6 months. The 2-part model was used for analysis. To examine the effect of COVID-19, beverage expenditure was analyzed after dividing it into short-term and long-term effects. Results: Our results show that the probability of purchasing alcoholic beverages increased owing to the long-term effect of the COVID-19 pandemic. The amounts of beer, wine, and traditional Korean liquor purchased increased in the long-term. The purchase of sweet drinks decreased (ie, fruit and vegetable juices and yogurt) in the long-term because of the effect of the pandemic. On the other hand, tea, water, and plant-based milk expenditures increased. Conclusion: This beverage consumption pattern reflects both unhealthy (ie, an increase in alcoholic beverage purchases) and healthy drinking behaviors (ie, a decrease in sweet beverage purchases and an increase in tea, water, and plant-based milk purchases).
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Host genetic polymorphisms are recognized as a critical determinant of diversity in clinical symptoms of Coronavirus disease 2019 (COVID-19). Accordingly, this study aimed to determine possible associations between single nucleotide polymorphisms (SNPs) in 37 candidate genes and clinical consequences of COVID-19 - especially long-term symptoms, Long COVID. A total of 260 COVID-19 patients, divided into mild (n=239) and severe (n=21) and further categorized based on the presence of Long COVID (no, n=211; yes, n=49), were recruited. Genotyping of selected polymorphisms in 37 genes responsible for viral entry, immune response, and inflammation was performed using MassARRAY system. Out of 37 SNPs, 9 including leucine zipper transcription factor like-1 (LZTFL1) rs10490770 C allele, LZTFL1 rs11385942 dupA allele, nicotinamide adenine dinucleotide synthetase-1 (NADSYN1) rs12785878 TT genotype, plexin A-4 (PLXNA4) rs1424597 AA genotype, LZTFL1 rs17713054 A allele, interleukin-10 (IL10) rs1800896 TC genotype and C allele, angiotensin converting enzyme-2 (ACE2) rs2285666 T allele, and plasmanylethanolamine desaturase-1 (PEDS1) rs6020298 GG genotype and G allele were significantly associated with an increased risk of developing Long COVID, whereas interleukin-10 receptor subunit beta (IL10RB) rs8178562 GG genotype was significantly associated with a reduced risk of Long COVID. Kaplan-Meier curve displayed that polymorphisms in the above genes were significantly associated with cumulative rate of Long COVID occurrence. Polymorphisms in LZTFL1 rs10490770, LZTFL1 rs11385942, LZTFL1 rs17713054, NADSYN1 rs12785878, PLXNA4 rs1424597, IL10 rs1800896, ACE2 rs2285666, PEDS1 rs6020298, and IL10RB rs8178562 appear to be genetic factors involved in development of Long COVID.
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There is an ongoing debate on the use of vitamin D supplementation in reducing the risk of influenza and COVID-19 infections and deaths. A recently published article highlights a relationship between vitamin D supplementation and reduced risk of COVID-19 and influenza. This comment aims to discuss the evidence on the use of Vitamin D in people who are at risk of developing COVID-19, focusing on safety issues of the Vitamin D supplementation.
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Background Addressing COVID-19 is a pressing health and social concern. To date, many epidemic projections and policies addressing COVID-19 have been designed without seroprevalence data to inform epidemic parameters. We measured the seroprevalence of antibodies to SARS-CoV-2 in Santa Clara County. Methods On 4/3-4/4, 2020, we tested county residents for antibodies to SARS-CoV-2 using a lateral flow immunoassay. Participants were recruited using Facebook ads targeting a representative sample of the county by demographic and geographic characteristics. We report the prevalence of antibodies to SARS-CoV-2 in a sample of 3,330 people, adjusting for zip code, sex, and race/ethnicity. We also adjust for test performance characteristics using 3 different estimates: (i) the test manufacturer's data, (ii) a sample of 37 positive and 30 negative controls tested at Stanford, and (iii) a combination of both. Results The unadjusted prevalence of antibodies to SARS-CoV-2 in Santa Clara County was 1.5% (exact binomial 95CI 1.11-1.97%), and the population-weighted prevalence was 2.81% (95CI 2.24-3.37%). Under the three scenarios for test performance characteristics, the population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%). These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April, 50-85-fold more than the number of confirmed cases. Conclusions The population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection is much more widespread than indicated by the number of confirmed cases. Population prevalence estimates can now be used to calibrate epidemic and mortality projections.
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Background: Vitamin D deficiency increases the risk of developing multiple sclerosis (MS) but it is unclear whether vitamin D supplementation improves the clinical course of MS, and there is uncertainty about the dose and form of vitamin D (D2 or D3) to be used. The mechanisms underlying the effects of vitamin D in MS are not clear. Vitamin D3 increases the rate of differentiation of primary oligodendrocyte precursor cells (OPCs), suggesting that it might help remyelination in addition to modulating the immune response. Here we analyzed the transcriptome of differentiating rat CG4 OPCs treated with vitamin D2 or with vitamin D3 at 24 h and 72 h following onset of differentiation. Methods: Gene expression in differentiating CG4 cells in response to vitamin D2 or D3 was quantified using Agilent DNA microarrays (n = 4 replicates), and the transcriptome data were processed and analysed using the R software environment. Differential expression between the experimental conditions was determined using LIMMA, applying the Benjamini and Hochberg multiple testing correction to p-values, and significant genes were grouped into co-expression clusters by hierarchical clustering. The functional significance of gene groups was explored by pathway enrichment analysis using the clusterProfiler package. Results: Differentiation alone changed the expression of about 10% of the genes at 72 h compared to 24 h. Vitamin D2 and D3 exerted different effects on gene expression, with D3 influencing 1272 genes and D2 574 at 24 h. The expression of the vast majority of these genes was either not changed in differentiating cells not exposed to vitamin D or followed the same trajectory as the latter. D3-repressed genes were enriched for Gene Ontology (GO) categories including transcription factors and the Notch pathway, while D3-induced genes were enriched for the Ras pathway. Conclusions: This study shows that vitamin D3, compared with D2, changes the expression of a larger number of genes in OLs. Identification of genes affected by D3 in OLs should help to identify mechanisms mediating its action in MS.
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Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)† to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources.
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The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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Objectives: The rapidly evolving coronavirus disease 2019 (COVID-19), was declared a pandemic by the World Health Organization on March 11, 2020. It was first detected in the city of Wuhan in China and has spread globally resulting in substantial health and economic crisis in many countries. Observational studies have partially identified the different aspects of this disease. Up to this date, no comprehensive systematic review for the clinical, laboratory, epidemiologic and mortality findings has been published. We conducted this systematic review and meta-analysis for a better understanding of COVID-19. Methods: We reviewed the scientific literature published from January 1, 2019 to March 3, 2020. Statistical analyses were performed with STATA (version 14, IC; Stata Corporation, College Station, TX, USA). The pooled frequency with 95% confidence intervals (CI) was assessed using random effect model. Publication bias was assessed and p <0.05 was considered a statistically significant publication bias. Results: Out of 1102 studies, 32 satisfied the inclusion criteria. A total of 4789 patients with a mean age of 49 years were evaluated. Fever (83.0%, CI 77.5 to 87.6), cough (65.2%, CI 58.6 to 71.2) and myalgia/fatigue (34.7, CI 26.0 to 44.4) were the most common symptoms. The most prevalent comorbidities were hypertension (18.5 %, CI 12.7 to 24.4) and Cardiovascular disease (14.9 %, CI 6.0 to 23.8). Among the laboratory abnormalities, elevated C-Reactive Protein (CRP) (72.0% (CI 54.3 to 84.6) and lymphopenia (50.1%, CI 38.0 to 62.4) were the most common findings. Bilateral ground-glass opacities (66.0%, CI 51.1 to 78.0) was the most common CT-Scan presentation. Pooled mortality rate was 6.6%, with males having significantly higher mortality compared to females (OR 3.4; 95% CI 1.2 to 9.1, P = 0.01). Conclusion: COVID-19 commonly presented with a progressive course of cough and fever with more than half of hospitalized patients showing leukopenia or a high CRP on their laboratory findings. Mortality associated with COVID19 was higher than that reported in studies in China with Males having a 3-fold higher risk of mortality in COVID19 compared to females.
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A serum vitamin D [25-hydroxyvitamin D, 25(OH)D] concentration of ≥75 nmol/L is recommended for optimal health. We investigated the relationship between serum 25(OH)D and metabolic syndrome (MetS), diabetes, cardiometabolic biomarkers, and cardiorespiratory fitness (CRF) in US adults using clinical cut points recommended by health organizations. Data from USA’s National Health and Nutrition Examination Surveys were used. Prevalences and likelihood of having MetS and diabetes according to clinical cut points for serum 25(OH)D (<30 nmol/L, 30-<50 nmol/L, 50-<75 nmo/L, and ≥75 nmol/L) were determined with multivariate logistic regression. Relations between serum 25(OH)D and various cardiometabolic biomarkers, CRF, MetS, and diabetes were tested using multivariable adjusted regression. Prevalence of MetS and diabetes were significantly lower in individuals with serum 25(OH)D ≥75 nmol/L (MetS, 21.6%; diabetes, 4.1%) compared to those with 25(OH)D <30 nmol/L (MetS, 45.5%; diabetes, 11.6%) (p < 0.0001). Individuals with serum 25(OH)D ≥75 nmol/L had significantly lower waist circumference (p < 0.0001), C-reactive protein (p = 0.003), glycated hemoglobin (p < 0.0002), fasting triglycerides (p < 0.0001), total homocysteine (p < 0.0001), and insulin resistance (p = 0.0001) and had significantly higher HDL-cholesterol (p < 0.0001) and maximal oxygen uptake (marker for CRF) (p< 0.0009) compared to those with 25(OH)D <30 nmol/L. In conclusion, serum 25(OH)D ≥75 nmol/L is associated with positive indicators related to cardiometabolic diseases in US adults.
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Aims: The purpose of this review was to investigate the effect of vitamin D supplements on hemoglobin concentration in subjects aged 17.5-68 years old; using randomized controlled trials (RCTs). Methods: Relevant RCT studies were identified from January 2000 to January 2019 by using MeSH terms in PubMed, Embase, Cochrane Library, Clinical trials, Scopus databases and gray literature. The studies were reviewed systematically, and quality assessments were evaluated by the guidelines of the Cochrane risk of bias. The effect of vitamin D supplements (n = 14) on hemoglobin concentration was considered as primary outcome, while its effects on the levels of ferritin, transferrin saturation and iron status were derived as secondary outcomes. In total, 1385 subjects with age range of 17.5 to 68 years old were examined for 3 h to 6 months; Mean (standard deviation) or median interquartile changes in the hemoglobin concentration in each treatment group was recorded for meta-analysis. Results: Fourteen RCTs met the inclusion criteria. Current study findings propose that vitamin D supplementation leads to a non-significant reduction in hemoglobin levels in subjects (17.5-68 years old) [std. mean difference (SMD): 0.01; 95% CI: - 0.28, 0.29; P = 0.95], also it has no significant effect on ferritin concentrations [std. mean difference (SMD): -0.01; 95% CI: [- 0.20, 0.18; P = 0.91]. However, vitamin D supplementation demonstrated positive effects on transferrin saturation [mean difference (MD): 1.54; 95% CI: 0.31, 2.76; P = 0.01] and iron status [std. mean difference (SMD): 0.24; 95% CI: - 0.09, 0.39; P = 0.002]. Conclusion: Current review concluded that supplementation with vitamin D had no significant effect on hemoglobin and ferritin levels while positive effects on transferrin saturation and iron status were observed. Further clinical studies are required to determine the actual effect of this intervention on hemoglobin levels.