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How to boost the immune defence prior to respiratory virus infections with the special focus on coronavirus infections



The emergence of the novel coronavirus SARS-CoV-2, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. One of the most worrying features of COVID-19 is a phenomenon known as the "cytokine storm", which is a rapid overreaction of the immune system. Additionally, coagulation abnormalities, thrombocytopenia and digestive symptoms, including anorexia, vomiting, and diarrhea, are often observed in critically ill patients with COVID-19. Baker's yeast β-glucan, a natural immunomodulatory component derived from Saccharomyces cerevisiae, primes the immune system to respond better to any microbial infection. Our previous studies have shown that oral administration of yeast β-glucans decreased the diarrhoea, modulated cytokine expression, and reduced the intestinal inflammation. Additionally, we showed that β-glucan fractions decreased coagulation in plasma and reduced the activation of platelets. During the period of home confinement facing individuals during the COVID-19 pandemic, our immune defence could be weakened by different factors, including stress, anxiety and poor nutrition, while a healthy diet rich in vitamins C and D can reinforce the immune defence and reduce the risk of microbial infections. Additionally, β-glucan can be used to strengthen the immune defence in healthy individuals prior to any possible viral infections. This short review focuses on the role of baker's yeast β-glucan, with a healthy diet rich in natural vitamins C and D, in addition to a healthy gut microbiota can provide synergistic immune system support, helping the body to naturally defend prior to respiratory virus infections, until stronger options such as vaccines are available.
Jawhara Gut Pathog (2020) 12:47
How toboost theimmune defence prior
torespiratory virus infections withthespecial
focus oncoronavirus infections
Samir Jawhara1,2*
The emergence of the novel coronavirus SARS-CoV-2, which causes severe respiratory tract infections in humans
(COVID-19), has become a global health concern. One of the most worrying features of COVID-19 is a phenomenon
known as the “cytokine storm”, which is a rapid overreaction of the immune system. Additionally, coagulation abnor-
malities, thrombocytopenia and digestive symptoms, including anorexia, vomiting, and diarrhea, are often observed
in critically ill patients with COVID-19. Baker’s yeast β-glucan, a natural immunomodulatory component derived from
Saccharomyces cerevisiae, primes the immune system to respond better to any microbial infection. Our previous stud-
ies have shown that oral administration of yeast β-glucans decreased the diarrhoea, modulated cytokine expression,
and reduced the intestinal inflammation. Additionally, we showed that β-glucan fractions decreased coagulation in
plasma and reduced the activation of platelets. During the period of home confinement facing individuals during
the COVID-19 pandemic, our immune defence could be weakened by different factors, including stress, anxiety and
poor nutrition, while a healthy diet rich in vitamins C and D can reinforce the immune defence and reduce the risk
of microbial infections. Additionally, β-glucan can be used to strengthen the immune defence in healthy individuals
prior to any possible viral infections. This short review focuses on the role of baker’s yeast β-glucan, with a healthy diet
rich in natural vitamins C and D, in addition to a healthy gut microbiota can provide synergistic immune system sup-
port, helping the body to naturally defend prior to respiratory virus infections, until stronger options such as vaccines
are available.
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e emergence of the novel coronavirus SARS-CoV-2,
which causes severe respiratory tract infections in
humans (COVID-19), has become a global health con-
cern [13]. Most coronaviruses cause animal infection
but can evolve into strains that are able to infect humans.
Coronaviruses, belonging to the family Coronaviridae, are
enveloped viruses with positive-stranded RNA [4]. Coro-
navirus entry into host cells is mediated by an envelope-
anchored spike (S) glycoprotein, which is responsible
for binding to a host receptor and then fusing viral and
host membranes [4]. e analysis of SARS-CoV-2 whole-
genome sequence causing COVID-19 is phylogeneti-
cally close to two bat-derived SARS-like coronaviruses,
bat-SL-CoVZC45 and bat-SL-CoVZXC2, first isolated in
Chinese horseshoe bats in 2015–2017 [5, 6]. Tang etal.
demonstrated that SARS-CoV-2 genome has evolved
into two major prevalent evolvement types, ‘L’ and ‘S’
types. e ‘L-type’, which emerged later from ‘S type’,
spreads quickly and is evolutionary more contagious and
aggressive than the S-type [7]. In terms of the interaction
between SARS-CoV-2 and its host, it has been reported
that angiotensin converting enzyme 2 (ACE 2) and ser-
ine protease TMPRSS2 are used by the spike protein of
SARS-CoV-2 to infect the lung cells as receptors similar
Open Access
Gut Pathogens
1 CNRS, UMR 8576, UGSF - Unité de Glycobiologie Structurale et
Fonctionnelle, INSERM U1285, Université Lille, 1 Place Verdun, 59000 Lille,
Full list of author information is available at the end of the article
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 2 of 6
Jawhara Gut Pathog (2020) 12:47
to those of SARS-CoV-1 [8, 9]. Additionally, other studies
showed that a high coexpression of ACE2 and TMPRSS2
was also detected in enterocytes, indicating that corona-
viruses may infect the gastrointestinal tract and the virus
activity may cause enzyme modifications, increasing the
susceptibility to intestinal inflammation and diarrhea [10,
11]. Of note, diarrhoea is a frequent symptom in corona-
virus infections, it was detected in up to 30% of patients
with MERS-CoV and 10.6% of patients with SARS-CoV
[12, 13]. Han etal. showed that COVID-19 patients with
mild disease severity marked by the presence of digestive
symptoms, in particular diarrhoea [14]. ese patients
showed a longer delay before viral clearance when com-
pared with those with only respiratory symptoms [14].
Viral RNAs, as pathogen-associated molecular patterns
(PAMPs), can be recognized by toll-like receptor (TLR)3,
TLR7, TLR8 and TLR9, cytosolic receptor melanoma
differentiation-associated gene 5, nucleotidyl-transferase
cyclic GMP-AMP synthase, and retinoic-acid inducible
gene I [1518]. Sensing of viral RNA by host receptors
activates downstream signalling pathways that lead to
the induction of immune responses by producing inflam-
matory cytokines including type I interferon (IFN) and
other mediators [19]. Plasma cytokines and chemokines
have been observed in COVID-19 patients infected with
SARS-CoV-2 [20, 21]. Of note, the SARS-CoV-2 parti-
cles first invade the respiratory mucosa and infect other
cell types, causing a series of immune responses and the
overproduction of cytokines ‘cytokine storm’, which may
be related to the critical condition of COVID-19 patients
Priming the immune system with immunomodulatory
components such as β-glucans can help to prevent the
production of a cytokine storm in the body. β-glucans are
major polymers of the Saccharomyces cerevisiae cell wall
structure [22]. ey play an important role in the struc-
ture and function of the yeast cell wall [22]. e cell wall
of S. cerevisiae contains two types of β-glucans. Branched
β-(1, 3)-glucan accounts for 50–55%, whereas β-(1,
6)-glucan represents 10–15% of total yeast cell wall poly-
saccharides [22]. Extraction of β-glucans from S. cerevi-
siae generally consists of two major steps including yeast
cell lysis (separation of the cell wall from the cytoplasm
and nucleic acids) and then alkaline hydrolysis with
spray-drying (extraction from insoluble cell wall) [23].
β-glucans derived from S. cerevisiae can initiate the
innate immune response and then trigger an effective
immune response including phagocytosis and cytokine
production that leads to fungal elimination [24, 25]. Dif-
ferent studies showed that β-glucans can act as a training
agent which results in amplified immune responses when
these trained immune cells are exposed to a secondary
stimulus [26, 27]. Netea etal. reported that training of
human monocytes with β-glucan promotes to enhanced
capacity of the immune response to eliminate not only
fungi, but also bacteria, viruses and even parasites [27].
e phenomenon of trained innate immunity follow-
ing exposure to β-glucan is accompanied by epigenetic
mechanisms involving histone modifications, reconfigu-
ration of chromatin and changes in metabolic function
that include increased aerobic glycolysis [28, 29]. ese
epigenetic modifications allow the innate immune cells
to acquire a memory phenotype of enhanced immune
responses when exposed to a secondary stimulus [28].
It has been reported that soluble β-glucans are recog-
nized by dendritic cells (DCs) and macrophages pre-
sent in Peyer’s patches and contributed to maturation of
DC through the dectin1 pathway [30]. In addition, we
showed that administration of β-glucans derived from
yeasts to mice diminished the overgrowth of Enterococcus
faecalis and Escherichia coli populations, and modulated
the production of inflammatory mediators [31]. β-glucan
administration increased the production of IL-10 via
activation of PPARγ, favouring the clearance of Candida
glabrata from the gut and the reduction of diarrhoea and
colitis [31]. In line with this observation, we showed that
in contrast to mannoprotein extracts, oral administration
of β-glucan derived from S. cerevisiae reduced intestinal
inflammation and promoted the reduction of C. albicans
overgrowth in the gut [23].
In terms of the effect of βglucans on viral infections,
administration of S. cerevisiae βglucan decreased pul-
monary lesion score and viral replication, and increased
IFNγ and NO levels in pigs infected with swine influ-
enza virus, indicating the role of βglucan as a prophy-
lactic option in decreasing of influenza virus infection
[32]. In line with this observation, young piglets were
exposed to porcine reproductive and respiratory syn-
drome virus and peripheral blood monocytes were then
isolated and exposed to varying concentrations of βglu-
can [33]. βglucan induced the production of IFNγ in a
dose-dependent manner, suggesting that soluble βglucan
may improve the innate immune response against this
virus [33]. Additionally, the administration of β-glucans
contained in the culture fluid of the yeast Aureobasidium
pullulans significantly increased the survival of mice
after sub-lethal infection with the PR8-H1N1 strain of
influenza virus [34]. Horst etal. showed that daily dietary
supplementation with β-1,3-glucan improved the vac-
cination response to Newcastle disease virus in chickens
With regard to the comparison of intense versus mod-
erate exercise, in contrast to moderate exercise that may
improve immune function, the high-intensity exercise
such as a marathon, can temporarily suppress mucosal
immunity, and increase the risk of developing upper
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Page 3 of 6
Jawhara Gut Pathog (2020) 12:47
respiratory tract infections [36]. Administration of β
glucan-derived from yeast induced the production of
salivary immunoglobulin A and reduced cold/flu symp-
tomatic days after intense exercise stress in a cohort of
182 individuals [36]. Further investigations showed that
βglucan supplementation decreased upper respiratory
tract infections and improved mood state in stressed
individuals, suggesting that it may be a useful approach
for reinforcing immune response against daily stressors
Multiple lines of evidence showed that β-glucans
derived from yeasts can block or activate many immune
receptors such as dectin-1, CD11b/CD18, or TLRs
[38, 39]. ese studies are consistent with our previous
reports showing that soluble β-glucans derived from
yeasts are able to modulate the activation of platelets
mediated by TLR4 expression [40]. In this study, we
showed that β-glucans at a low concentration in plasma
decreases thrombin production and the progressive
increase in β-glucan concentration in plasma reduces
coagulation until these β-glucan fractions no longer
affect thrombin production indicating that β-glucan frac-
tions have activity that is similar to that of low molecu-
lar weight heparin [40]. Additionally, β-glucan fractions
decreased the platelet aggregation and the expression
of receptors such as P-selectin and activation of integ-
rin αIIbβ3. It also reduced platelet activation mediated
by TLR4 by increasing the production of TGF-β1 and
release of ATP [40]. Of note, platelets play an impor-
tant role in haemostasis, inflammation and pathogen
clearance [24]. Recently, a decrease in platelet count has
been observed in patients with SARS-CoV-2 [41]. ese
patients with COVID-19 are at high risk of developing
disseminated intravascular coagulation (DIC) and both
thrombocytopenia and elevated D-dimer are induced in
these patients by the excessive activation of the coagu-
lation cascade and platelets [42]. Multiple pathogenetic
mechanisms are involved, including endothelial dysfunc-
tion, von Willebrand factor elevation, and TLR activa-
tion. ese data suggest that the use of prophylactic dose
low molecular weight heparin (LMWH) as prophylaxis
and monitoring the coagulation status by measuring pro-
thrombin time, platelet count, and D-dimer concentra-
tions in critically ill patients with COVID-19 [42, 43]. In
line with these clinical observations, severe COVID-19
is also associated with increased concentrations of pro-
inflammatory cytokines including IL-6 which can induce
tissue factor expression on mononuclear cells that initi-
ates coagulation, platelet activation and thrombin gener-
ation [20]. Recently, a monoclonal antibody against IL-6
(tocilizumab) emerged as an alternative treatment for
COVID19 patients with a risk of cytokine storms. Guo
etal. showed that anti-IL-6 antibody treatment reduced
the overreaction of the inflammatory immune responses
and boosted immune responses mediated by B cells and
CD8 + T cells [44].
Currently, lifestyle changes and psychosocial stress
caused by home confinement during the COVID-19 pan-
demic could disturb our immune defences. Shimamiya
etal. showed that the percentage of CD69+ lymphocy tes
decreased during the confinement period [45]. is was
mostly caused by changes in the ratio of natural killer
(NK) to non-NK lymphocytes suggesting that the stress
caused by confinement plays a role in the immune changes
observed [45]. Different studies have shown that βglucan
has a significant role in stress reduction via the inhibition
of corticosterone levels and modulation of cytokine pro-
duction [46, 47]. Baker’s yeast βglucan combined with a
healthy diet rich in vitamins C and D can be used to boost
the immune defence in healthy individuals prior to any
possible viral infection. Závorková etal. showed that sup-
plementation with βglucan and vitamin D in patients with
diabetic retinopathy resulted in significant improvements
in high-density lipoprotein levels and a large decrease in
total level of cholesterol, supporting the view that βglu-
can and vitamin D supplementation has a positive effect
on human health [48]. In line with this observation, βglu-
can can also increase the effects of vitamin D with positive
changes in apolipoprotein A1 metabolism in patients with
diabetic retinopathy [49]. Additionally, several studies have
demonstrated beneficial effects when βglucan was given
in combination with vitamin C [47, 50, 51]. An experimen-
tal study revealed that combination of glucan-vitamin C
showed notable healing abilities in the treatment of infec-
tion by Mesocestoides corti [50]. Konno etal. pointed out
that synergistic potentiation of βglucan with vitamin C
may improve the efficacy of current treatments for various
human cancers [52].
Vitamins C and D are well-known to boost the immune
response against viral infections [5357] (Fig.1). ese
vitamins have both been implicated in the immune
response to several types of respiratory infections,
including influenza, respiratory syncytial virus and tuber-
culosis [5357]. Hansdottir etal. showed that vitamin D
reduces the inflammatory response to respiratory syncy-
tial virus via decreasing the production of cytokines and
chemokines in the airways epithelium while maintaining
the antiviral state [55]. In addition to vitamins C and D,
vitamins B, E, omega-3 fatty acids, carotenoids, polyphe-
nols (flavonoids, phenolic acids), and some minerals (Zn,
Mn, Cu, Se) can provide health benefits by a synergistic
effect, maintaining a proper redox homeostasis [5860].
In terms of SARS-CoV-2, vitamin D was employed in
the early nutritional supplementation of non-critically ill
patients hospitalized for COVID-19 disease [61]. Addi-
tionally, vitamin D can modulate the immune response
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Page 4 of 6
Jawhara Gut Pathog (2020) 12:47
by reducing the cytokine storm induced by the innate
immune system, such as tumour-necrosis factor (TNF)-α
and IFN-γ [62].
Further investigations demonstrated that elevated vita-
min D levels in healthy individuals are associated with
down-regulation of pro-inflammatory cytokine production
through decreased expression of TLR4 [63]. Grant et al.
showed that vitamin D supplementation could reduce the
incidence, severity and risk of death from COVID-19 [64].
Recently, Munshi etal. showed an association of vitamin D
serum levels with COVID-19 severity and prognosis [65].
Patients with poor prognosis had significantly lower serum
levels of vitamin D compared to those with good progno-
sis supporting that serum vitamin D levels could be impli-
cated in the COVID-19 prognosis and diagnosis of vitamin
D deficiency could be a helpful adjunct in assessing patients’
potential of developing severe COVID-19 [65].
In addition to vitamin D, vitamin C has been proposed to
prevent and treat COVID-19 [66]. A new clinical trial has
begun in Wuhan, China, to investigate the role of vitamin C
infusion in the treatment of severe SARS-CoV-2 pneumonia
Vitamin D also plays an important role in the gut by
reinforcing the integrity of the intestinal barrier and
enhancing the tight junctions that control mucosal per-
meability [67]. e gut microbiota can also be disrupted
by stress and poor nutrition during the COVID-19 lock-
down. Microbiota diversity is crucial to maintain bar-
rier defences, gut homeostasis and to resist stress, gut
infections or metabolic changes. It has been shown that
changing the diet to one rich in refined carbohydrates
including processing of simple sugars and animal fat leads
to an important disruption of the gut microbiota diversity
[68]. e gut-lung axis is well-known through cell wall
components of the gut microbiota and their metabolites
such as short-chain fatty acids that can interact with host
PRRs and modulate the immune response [6971]. With
regard to the role of the gut microbiota in the immu-
nomodulation of virus infection, it has been shown that
influenza infection can alter the intestinal microbial
community by reducing commensal anaerobic bacteria
and increasing the Proteobacteria gut population. is
occurs via a mechanism that is dependent on type I inter-
ferons induced in the pulmonary tract suggesting that
Fig. 1 Schematic overview of how to boost the immune defence prior to respiratory virus infections with a healthy diet including baker’s yeast
βglucan as a prophylactic option, with a healthy diet rich in natural vitamins (A, B, C, D, and E), minerals (Zn, Mn, Cu, Se), omega-3 fatty acids,
polyphenols, and healthy microbiota
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Page 5 of 6
Jawhara Gut Pathog (2020) 12:47
influenza-induced type I interferons may facilitate sec-
ondary Salmonella infection [72]. Recently, Zhejiang etal.
observed that some patients with COVID-19 have a dis-
rupted gut microbiota with decreased Lactobacillus and
Bifidobacterium populations [73]. Nutritional support
and administration of prebiotics or probiotics were pro-
posed to these COVID-19 patients to regulate the balance
of the intestinal microbiota and reduce the risk of second-
ary infections [73]. It therefore appears that it would be
better to have a healthy gut microbiota with a high biodi-
versity prior to any viral infection including coronavirus.
Overall, a combination of baker’s yeast βglucan as a
prophylactic option, with a healthy diet rich in natural
vitamins C and D, can provide synergistic immune sys-
tem support, helping the body to naturally defend against
viruses. Finally, although all these strategies developed
in this short review can help to naturally improve our
immune response against any viral infection, still the vac-
cine, such as the SARS-CoV-2 vaccine when it will be
widely available, is the best option to efficiently stop fur-
ther spread of this virus causing the deadly COVID-19.
Not applicable.
Authors’ contributions
SJ drafted this review. The author read and approved the final manuscript.
This work was partially funded by the Agence Nationale de la Recherche
(ANR) in the setting of project “InnateFun”, promotional reference ANR-16-
IFEC-0003-05, in the “Infect-ERA” program.
Availability of data and materials
Not applicable.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The author declares no conflict of interest.
Author details
1 CNRS, UMR 8576, UGSF - Unité de Glycobiologie Structurale et Fonctionnelle,
INSERM U1285, Université Lille, 1 Place Verdun, 59000 Lille, France. 2 University
of Lille, 59000 Lille, France.
Received: 17 April 2020 Accepted: 3 October 2020
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... By increasing circulating monocytes and neutrophils and increasing neutrophil oxidative microbicidal activity without generating harmful inflammatory responses, b-glucans enhanced the clearance of antibiotic-resistant S. aureus in a rat intra-abdominal infection model (30,34). Daily dietary supplementation with b-glucan improved the vaccination response to Newcastle disease virus in chickens (35). A combination of b-glucan and vitamin C also improved healing in the treatment of infection by M. corti (35). ...
... Daily dietary supplementation with b-glucan improved the vaccination response to Newcastle disease virus in chickens (35). A combination of b-glucan and vitamin C also improved healing in the treatment of infection by M. corti (35). Yeast-based glucans have been applied in clinical studies of bacterial and viral infections. ...
... Another yeast-derived b-glucan was able to protect mice infected with a lethal titer of the A/Puerto Rico/8/34 (PR8; H1N1) strain of influenza virus (38). In pigs infected with swine influenza virus, administration of S. cerevisiae yeast b-glucan decreased pulmonary lesion score and viral replication along with an increase in IFN-g and NO levels (35). ...
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Sepsis is a life-threatening condition caused by an abnormal immune response induced by infection with no approved or specific therapeutic options. We present our perspectives for the therapeutic management of sepsis through a four-way approach: (1) infection control through immune enhancement; (2) immune suppression during the initial hyper-inflammatory phase; (3) balanced immune-modulation to counter the later immune-paralysis phase; and (4) advantageous effects on metabolic and coagulation parameters throughout. COVID-19 is a virus-triggered, accelerated sepsis-like reaction that is associated with the rapid progress of an inflammatory cascade involving a cytokine storm and multiorgan failure. Here, we discuss the potential of the biological response modifiers, β-glucans (BRMGs), in the management of sepsis based on their beneficial effects on inflammatory-immune events in COVID-19 clinical studies. In COVID-19 patients, apart from metabolic regulation, BRMGs, derived from a black yeast, Aureobasidium pullulans strain AFO-202, have been reported to stimulate immune responses. BRMGs, produced by another strain (N-163) of A. pullulans, have been implicated in the beneficial regulation of inflammatory markers and immunity, namely IL-6, C-reactive protein (CRP), D-Dimer, ferritin, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein ratio (LCR), leucocyte-to-C-reactive protein ratio (LeCR), and leukocyte-to-IL-6 ratio (LeIR). Agents such as these β-glucans, which are safe as they have been widely consumed by humans for decades, have potential as adjuncts for the prevention and management of sepsis as they exert their beneficial effects across the spectrum of processes and factors involved in sepsis pathology, including, but not limited to, metabolism, infection, inflammation, immune modulation, immune enhancement, and gut microbiota.
... The 1,3-1,6-beta-glucans are considered to be the best biological response modifiers and have immunogenic properties [176]. Most glucans with this chain structure are derived from macrofungi (mushrooms) or yeast [172,177]. The hypothesis posed by Galler and Yan [172] was corroborated by other authors, who found that β-glucans from mushrooms demonstrated the potential for the treatment of lung injury [178]. ...
... [ 169,177,191] The promising results of studies on mushroom β-glucan from Agaricus bisporus and Lentinula edodes [14,175] allow us to assume a beneficial effect of these compounds in the prevention, course, and counteracting complications of COVID-19 in the era of the pandemic caused by SARS-CoV-2. Still, there are only a few studies on the promising function of mushroom β-glucans in the context of COVID-19; such research needs to be continued due to the easy availability and significant amounts of beta-glucans in mushrooms [35], as well as the safety and ease of administration without significant side effects, even in the case of insufficient purification [14,186,187]. ...
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Beta-glucans comprise a group of polysaccharides of natural origin found in bacteria, algae, and plants, e.g., cereal seeds, as well as microfungi and macrofungi (mushrooms), which are characterized by diverse structures and functions. They are known for their metabolic and im-munomodulatory properties, including anticancer, antibacterial, and antiviral. Recent reports suggest a potential of beta-glucans in the prevention and treatment of COVID-19. In contrast to β-glucans from other sources, β-glucans from mushrooms are characterized by β-1,3-glucans with short β-1,6-side chains. This structure is recognized by receptors located on the surface of immune cells; thus, mushroom β-glucans have specific immunomodulatory properties and gained BRM (biological response modifier) status. Moreover, mushroom beta-glucans also owe their properties to the formation of triple helix conformation, which is one of the key factors influencing the bioac-tivity of mushroom beta-glucans. This review summarizes the latest findings on biological and health-promoting potential of mushroom beta-glucans for the treatment of civilization and viral diseases, with particular emphasis on COVID-19.
... BCG vaccination (178,179) or the administration of mucosal immunotherapies such as Trained Immunity-based Vaccines (TIbV) (180) have been shown to confer protection against SARS-CoV-2 infection. Along this line, prophylactic treatments based on b-glucans (181) or their incorporation through the diet (182) have been proposed to serve as a defense against COVID-19, but experimental data are still scarce in this topic. ...
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The C-type lectin receptor Dectin-1 was originally described as the β-glucan receptor expressed in myeloid cells, with crucial functions in antifungal responses. However, over time, different ligands both of microbial-derived and endogenous origin have been shown to be recognized by Dectin-1. The outcomes of this recognition are diverse, including pro-inflammatory responses such as cytokine production, reactive oxygen species generation and phagocytosis. Nonetheless, tolerant responses have been also attributed to Dectin-1, depending on the specific ligand engaged. Dectin-1 recognition of their ligands triggers a plethora of downstream signaling pathways, with complex interrelationships. These signaling routes can be modulated by diverse factors such as phosphatases or tetraspanins, resulting either in pro-inflammatory or regulatory responses. Since its first depiction, Dectin-1 has recently gained a renewed attention due to its role in the induction of trained immunity. This process of long-term memory of innate immune cells can be triggered by β-glucans, and Dectin-1 is crucial for its initiation. The main signaling pathways involved in this process have been described, although the understanding of the above-mentioned complexity in the β-glucan-induced trained immunity is still scarce. In here, we have reviewed and updated all these factors related to the biology of Dectin-1, highlighting the gaps that deserve further research. We believe on the relevance to fully understand how this receptor works, and therefore, how we could harness it in different pathological conditions as diverse as fungal infections, autoimmunity, or cancer.
... Gram staining of Clostridium will show large gram-positive rods, with a paucity of leukocytes (as is typical of anaerobic infections) [2], while Escherichia coli shows gram-negative rods, and Enterococcus faecium shows gram-positive cocci [20,21]. In this case, the medical group did not perform Gram staining due to the clinical laboratory chaos caused by the coronavirus disease 2019 (COVID-19) outbreak at the beginning of last year [22,23]. However, because cellular morphology and arrangement are insufficient for differentiating the species directly, Gram strains, although efficient and compensatory, are sometimes the only distinguishing characteristic while cultures and subsequent drug sensitivity experiments are still the conventional critical tests for early and accurate pathogen diagnosis. ...
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Background Gas-producing perianal abscess raises the possibility of clostridial infection, with Clostridium perfringens being the most common causative agent, which is highly lethal if untreated timely. As the treatment of clostridial infections often differs from that of non-clostridial infections, which they may closely resemble, the importance of accurate pathogenic organism identification cannot be overemphasized. The 16S rDNA of bacteria is highly conserved within a species and among species of the same genus but demonstrates substantial variation between different species, thus making it a suitable genomic candidate for bacterial detection and identification. Case presentation Here, we report the case of a 53-year-old patient who was admitted to the hospital for a gas-producing perianal abscess. The patient was managed with ceftizoxime and ornidazole and then received debridement and drainage at the lesion on the second day after admission. The bacterial cultures of the patient isolates from the debridement showed a coinfection of Escherichia coli and Enterococcus faecium. Although perianal redness and swelling subsided obviously after the surgery, the patient was febrile to 38.3℃ with his left upper thigh red and swollen, aggravated with tenderness and crepitus. Considering insufficient debridement and the risk of incorrect identification of pathogens, a second debridement and drainage were performed 4 days after the primary operation, and 16S rDNA sequencing of the isolates implicated Clostridium perfringens infection. Given the discrepancies in diagnostic results and the treatment outcomes, Enterococcus faecium was identified as sample contamination, and a diagnosis of coinfection of Clostridium perfringens and Escherichia coli in gas-producing perianal abscess was confirmed. The patient was then successfully treated with meropenem and vancomycin and was discharged at 27 days of admission. Conclusions This case represents the first report of coinfection of both clostridial and non-clostridial organisms in gas-producing perianal abscess and the first case reporting the use of 16S rDNA sequencing in the diagnosis of perianal abscess. Timely pathogen identification is critical for treating gas-producing perianal abscess and an antibiotic regimen covering both aerobic and anaerobic organisms is recommended before true pathogens are identified.
... COVID-19 tedavi ve önlenmesinde beta-glukanın kullanıldığı randomize kontrollü herhangi bir çalışma verisi yoktur. Önceki çalışmalara dayanarak oral beta-glukan kullanımının bağışıklık yanıtını destekleyebileceği, intestinal inflamasyonu ve tromboz riskini azaltabileceği, COVID-19 profilaksi ve tedavisinde için etkili, düşük maliyetli ve güvenli bir yol olabileceği varsayılabilir ancak bu tedavinin güvenliğini ve etkinliğini doğrulamak için klinik araştırmalar gerekmektedir [61] . ...
... Therefore, without a cure or well-proven vaccine until now against SARS-COV-2 and the problems associated with other respiratory infections, a healthy eating pattern is essential to strengthen our body's defenses and improve response to these respiratory disease-causing agents (BourBour et al., 2020;Lin et al., 2016). Faced with the restrictions that we are currently experiencing, it is crucial to take care of our diet to maintain our health and ensure the strengthening of our immune system, that is, our body's natural defense against respiratory infections (Jawhara, 2020;Junaid et al., 2020;Roy et al., 2020). Therefore, it is easy comprehensible that a well-balanced diet is key to body homeostasis and in to preventing respiratory infections. ...
Background Korean traditional food (KTF), originated from ancestral agriculture and the nomadic traditions of the Korean peninsula and southern Manchuria, is based on healthy food that balances disease prevention and treatment. Fermented foods that include grains, herbs, fruits, and mushrooms are also an important practice in KTF, providing high levels of Lactobacilli, which confer relevant health benefits, including antiviral properties. Some of these probiotics may also protect against the Influenza virus through the modulation of innate immunity. Scope and approach The emerging of the COVID-19 pandemic, in addition to other diseases of viral origin, and the problems associated with other respiratory disorders, highlight how essential is a healthy eating pattern to strengthen our immune system. Key Findings and Conclusions: The present review covers the information available on edible plants, herbs, mushrooms, and preparations used in KTF to outline their multiple medicinal effects (e.g., antidiabetic, chemopreventive, antioxidative, anti-inflammatory, antibacterial), emphasizing their role and effects on the immune system with an emphasis on modulating properties of the gut microbiota that further support strong respiratory immunity. Potential functional foods commonly used in Korean cuisine such as Kimchi (a mixture of fermented vegetables), Meju, Doenjang, Jeotgal, and Mekgeolli and fermented sauces, among others, are highlighted for their great potential to improve gut-lung immunity. The traditional Korean diet and dietary mechanisms that may target viruses ACE-2 receptors or affect any step of a virus infection pathway that can determine a patient's prognosis are also highlighted. The regular oral intake of bioactive ingredients used in Korean foods can offer protection for some viral diseases, through protective and immunomodulatory effects, as evidenced in pre-clinical and clinical studies.
Background and study aim: Anti-Saccharomyces cerevisiae antibodies (ASCA) have been described in many autoimmune diseases (AIDs). Coronavirus disease 2019 (COVID-19) could trigger AIDs. This study aimed to determine the frequency of ASCA in patients with COVID-19. Patients and methods This study included 88 adult patients with severe COVID-19, 51 mild COVID-19, and 160 healthy blood donors. ASCA of isotype immunoglobulin (Ig)G and IgA were detected by enzyme-linked immunosorbent assay. Results The frequency of ASCA (IgG or IgA) was significantly higher in patients with severe COVID-19 (21.6% vs. 3.7%, p < 10⁻⁻³) and in patients with mild COVID-19 than in the healthy controls (13.7% vs. 3.7%, p = 0.03). ASCA-IgA was significantly more frequent in patients with severe COVID-19 than in healthy controls (15.9% vs. 0.6%, p < 10⁻³). ASCA-IgG was significantly more frequent in patients with mild COVID-19 than in healthy controls (13.7% vs. 3.1%, p = 0.02). ASCA (IgG or IgA) were more frequent in severe than in mild COVID-19, but the difference was not statistically significant (21.6% vs. 13.7%). ASCA-IgA was significantly more frequent in patients with severe than those with mild COVID-19 (15.9% vs. 0%, p = 0.003). The mean ASCA-IgG and ASCA-IgA levels were significantly higher in patients with severe COVID-19 than in healthy controls (5.8 U/mL ± 11.8 vs. 2.3 U/mL ± 2.8, p < 10⁻³ and 9.2 U/mL ± 21.5 vs. 3.4 U/mL ± 1.7, respectively, p < 10⁻³). The mean ASCA-IgG levels were significantly higher in patients with mild COVID-19 than in healthy controls (6.2 U/mL ± 12.9 vs. 2.3 U/mL ± 2.8, p < 10⁻³). The mean ASCA-IgA levels were significantly higher in patients with severe than in those with mild COVID-19 (9.2 U/mL ± 21.5 vs. 2.6 U/mL ± 1.2, p = 0.03). Conclusion ASCA was more frequent in patients with COVID-19 than in healthy controls.
Numerous guidelines on how to write a scientific article have been published. Many books and articles giving detailed instructions on how to develop a research question, perform a literature search, or design a study protocol are widely available. However, there are few guidelines on how to create logical flow when writing a scientific article. Logical flow is the key to achieving a smooth and orderly progression of ideas, sentences, paragraphs, and content towards a convincing conclusion. This article provides guidelines for creating logical flow when writing the text and main sections of a scientific article. The first step is creating a draft outline of the whole article. Once completed, the draft outline is developed into a single, coherent article that logically explains the study. Logical flow in the text is created by using precise and concise words, composing clear sentences, and connecting well-structured paragraphs. The use of transitions connects sentences and paragraphs, ensuring clarity and coherence when presenting academic arguments and conclusions. Logical flow in the main sections of a scientific article is achieved by presenting the whole story of the article sequentially in the introduction, methods, results, and discussion, focusing attention on the most important points in each section, and connecting all of these to the main purpose of the study.
General purpose: To present a scoping review of preclinical and clinical trial evidence supporting the efficacy and/or safety of major alternative wound care agents to summarize their effects on validated elements of wound bed preparation and wound management paradigms. Target audience: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. Learning objectives/outcomes: After participating in this educational activity, the participant will:1. Differentiate the effectiveness of the topical wound care agents included in this review.2. Compare the preventive efficacy of intravenous agents administered to trauma and surgical patients.3. Select the effectiveness of products in this review that are left in place after surgical procedures.4. Identify an oral agent that can be helpful in mitigating the effects of COVID-19.
We propose that hyper-inflammation (HYPi) is a ''runaway'' consequence of acute inflammation (ACUi) that arises more easily (and also abates less easily) in those who host a pre-existing chronic inflammation (CHRi), because (i) most factors involved in generating an ACUi to limit viral proliferation are already present when there is an underlying CHRi, and also because (ii) anti-inflammatory (AI) mechanisms for the abatement of ACUi (following containment of viral proliferation) are suppressed and desensitized where there is an underlying CHRi, with this causing the ACUi to spiral into a HYPi. Stress, pollution, diet, and gut microbiomes (alterable in weeks through dietary changes) have an intimate and bidirectional cause-effect relationship with CHRi. We propose that avoidance of CHRi-promoting foods and adoption of CHRi-suppressing foods could reduce susceptibility to HYPi, in Covid-19 and in other viral diseases, such as influenza, which are characterized by episodic and unpredictable HYPi.
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The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses had two major lineages (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. We found that L lineage was more prevalent than the S lineage within the limited patient samples we examined. The implication of these evolutionary changes on disease etiology remains unclear. These findings strongly underscores the urgent need for further comprehensive studies that combine viral genomic data, with epidemiological studies of coronavirus disease 2019 (COVID-19).
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Several studies show that the immunosuppressive drugs targeting the interleukin-6 (IL-6) receptor, including tocilizumab, ameliorate lethal inflammatory responses in COVID-19 patients infected with SARS-CoV-2. Here, by employing single-cell analysis of the immune cell composition of two severe-stage COVID-19 patients prior to and following tocilizumab-induced remission, we identify a monocyte subpopulation that contributes to the inflammatory cytokine storms. Furthermore, although tocilizumab treatment attenuates the inflammation, immune cells, including plasma B cells and CD8⁺ T cells, still exhibit robust humoral and cellular antiviral immune responses. Thus, in addition to providing a high-dimensional dataset on the immune cell distribution at multiple stages of the COVID-19, our work also provides insights into the therapeutic effects of tocilizumab, and identifies potential target cell populations for treating COVID-19-related cytokine storms.
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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Currently, several vaccine candidates against SARS-CoV-2 are in clinical trials but approval of these vaccines is likely to take a long time before they are available for public use. In a previous report, the importance of passive immunity and how immunoglobulin (Ig)G collected from recovered coronavirus patients could help in the protection against COVID-19 and boost the immune system of new patients was reported. Passive immunity by immunoglobulin transfer is a concept employed by most mammals and bovine IgG has a role to play in human therapy. IgG is one of the major components of the immunological activity found in cow's milk and colostrum. Heterologous transfer of passive immunity associated with the consumption of bovine immune milk by humans has been investigated for decades for its immunological activity against infections. This short review focuses on passive immunity and how microfiltered raw immune milk or colostrum collected from cows vaccinated against SARS-CoV-2 could provide short-term protection against SARS-CoV-2 infection in humans and could be used as an option until a vaccine becomes commercially available.
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Background As an immune modulator, vitamin D has been implicated in the Coronavirus disease‐2019 (COVID‐19) outcome. We aim to systematically explore the association of vitamin D serum levels with COVID‐19 severity and prognosis. Methods The standardized mean difference (SMD) or odds ratio and 95% confidence interval (CI) were applied to estimate pooled results from seven studies. The prognostic performance of vitamin D serum levels for predicting adverse outcomes with detection of the best cutoff threshold was determined by ROC curve analysis. Decision tree analysis by combining vitamin D levels and clinical features was applied to predict severity in COVID‐19 patients. Results Mean vitamin D serum level of 1,368 patients, was 22.9 nmol/L (21.9‐23.8). Significant heterogeneity was found (I² = 99.9%, P< 0.001). Patients with poor prognosis (N=634) had significantly lower serum levels of vitamin D compared to those with good prognosis (N=669), representing an adjusted standardized mean difference of ‐5.12 (95% Cl= ‐9.14 to ‐1.10, P = 0.012). Conclusion Serum vitamin D levels could be implicated in the COVID‐19 prognosis. Diagnosis of vitamin D deficiency could be a helpful adjunct in assessing patients' potential of developing severe COVID‐19. Appropriate preventative and/or therapeutic intervention may improve COVID‐19 outcomes. This article is protected by copyright. All rights reserved.
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Platelets are essential for vascular repair and for the maintenance of blood homeostasis. They contribute to the immune defence of the host against many infections caused by bacteria, viruses and fungi. Following infection, platelet function is modified, and these cells form aggregates with microorganisms leading, to a decrease in the level of circulating platelets. During candidaemia, mannans, β-glucans and chitin, exposed on the cell wall of Candida albicans, an opportunistic pathogenic yeast of humans, play an important role in modulation of the host response. These fungal polysaccharides are released into the circulation during infection and their detection allows the early diagnosis of invasive fungal infections. However, their role in the modulation of the immune response and, in particular, that of platelets, is not well understood. The structure and solubility of glycans play an important role in the orientation of the immune response of the host. This short review focuses on the effect of fungal β-glucans and chitin on platelet activation and how these glycans modulate platelet activity via Toll-like receptors, contributing to the escape of C. albicans from the immune response.
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Objectives: Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. Methods: We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected ≥24 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. Results: There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 ± 3.1 days and a frequency of 4.3 ± 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 ± 7.7 vs 11.6 ± 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P = 0.033) than those with respiratory symptoms. Discussion: We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.
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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.
In terms of public health, the 21st century has been characterized by coronavirus pandemics: in 2002-03 the virus SARS-CoV caused SARS; in 2012 MERS-CoV emerged and in 2019 a new human betacoronavirus strain, called SARS-CoV-2, caused the unprecedented COVID-19 outbreak. During the course of the current epidemic, medical challenges to save lives and scientific research aimed to reveal the genetic evolution and the biochemistry of the vital cycle of the new pathogen could lead to new preventive and therapeutic strategies against SARS-CoV-2. Up to now, there is no cure for COVID-19 and waiting for an efficacious vaccine, the development of “savage” protocols, based on “old” anti-inflammatory and anti-viral drugs represents a valid and alternative therapeutic approach. As an alternative or additional therapeutic/preventive option, different in silico and in vitro studies demonstrated that small natural molecules, belonging to polyphenols family, can interfere with various stages of coronavirus entry and replication cycle. Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PLpro, 3CLpro, NTPase/helicase. Due to their pleiotropic activities and lack of systemic toxicity, flavonoids and their derivative may represent target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.
Objectives Beginning in December 2019, the 2019 novel coronavirus disease (COVID-19) has caused a pneumonia epidemic that began in Wuhan, China, and is rapidly spreading throughout the whole world. Italy is the hardest hit country after China. Considering the deleterious consequences of malnutrition, which certainly can affect patients with COVID-19, the aim of this study is to present a pragmatic protocol for early nutritional supplementation of non-critically ill patients hospitalized for COVID-19 disease. It is based on the observation that most patients present at admission with severe inflammation and anorexia leading to a drastic reduction of food intake, and that a substantial percentage develops respiratory failure requiring non-invasive ventilation or even continuous positive airway pressure. Methods High-calorie dense diets in a variety of different consistencies with highly digestible foods and snacks are available for all patients. Oral supplementation of whey proteins as well as intravenous infusion of multivitamin, multimineral trace elements solutions are implemented at admission. In the presence of 25-hydroxyvitamin D deficit, cholecalciferol is promptly supplied. If nutritional risk is detected, two to three bottles of protein-calorie oral nutritional supplements (ONS) are provided. If <2 bottles/d of ONS are consumed for 2 consecutive days and/or respiratory conditions are worsening, supplemental/total parenteral nutrition is prescribed. Conclusion We are aware that our straight approach may be debatable. However, to cope with the current emergency crisis, its aim is to promptly and pragmatically implement nutritional care in patients with COVID-19, which might be overlooked despite being potentially beneficial to clinical outcomes and effective in preventing the consequences of malnutrition in this patient population.