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Do an Altered Gut Microbiota and an Associated Leaky Gut Affect COVID-19 Severity?

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Coronavirus disease 2019 (COVID-19), which has been declared a pandemic, has exhibited a wide range of severity worldwide. Although this global variation is largely affected by socio-medical situations in each country, there is also high individual-level variation attributable to elderliness and certain underlying medical conditions, including high blood pressure, diabetes, and obesity. As both elderliness and the aforementioned chronic conditions are often associated with an altered gut microbiota, resulting in disrupted gut barrier integrity, and gut symptoms have consistently been associated with more severe illness in COVID-19 patients, it is possible that dysfunction of the gut as a whole influences COVID-19 severity. This article summarizes the accumulating evidence that supports the hypothesis that an altered gut microbiota and its associated leaky gut may contribute to the onset of gastrointestinal symptoms and occasionally to additional multiorgan complications that may lead to severe illness by allowing leakage of the causative coronavirus into the circulatory system.
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Do an Altered Gut Microbiota and an Associated Leaky Gut
Affect COVID-19 Severity?
Heenam Stanley Kim
a
a
Division of Biosystems & Biomedical Sciences, College of Health Sciences, Korea University, Seoul, Republic of Korea
ABSTRACT Coronavirus disease 2019 (COVID-19), which has been declared a pan-
demic, has exhibited a wide range of severity worldwide. Although this global varia-
tion is largely affected by socio-medical situations in each country, there is also high
individual-level variation attributable to elderliness and certain underlying medical
conditions, including high blood pressure, diabetes, and obesity. As both elderliness
and the aforementioned chronic conditions are often associated with an altered gut
microbiota, resulting in disrupted gut barrier integrity, and gut symptoms have con-
sistently been associated with more severe illness in COVID-19 patients, it is possible
that dysfunction of the gut as a whole inuences COVID-19 severity. This article sum-
marizes the accumulating evidence that supports the hypothesis that an altered gut
microbiota and its associated leaky gut may contribute to the onset of gastrointesti-
nal symptoms and occasionally to additional multiorgan complications that may lead
to severe illness by allowing leakage of the causative coronavirus into the circulatory
system.
KEYWORDS COVID-19, SARS-CoV-2, coronavirus, gut microbiota, gut barrier integrity,
leaky gut
KEY MESSAGES
While the following remains to be empirically demonstrated, accumulating
evidence supports the hypothesis that an altered gut microbiota and an
associated leaky gut may contribute to the onset of coronavirus disease 2019
(COVID-19)-related gastrointestinal symptoms, such as diarrhea and, in severe
cases, multiorgan complications.
Testing for a leaky gut and fecal and plasma viral loads may be useful for
diagnosing the seriously ill or for preventing transmission by fecal shedding of the
virus.
Fecal microbiota transplantation (FMT), next-generation probiotics focusing on
butyrate-producing gut microbes, or simply increasing the daily intake of dietary
ber may be considered in improving the gut health of COVID-19 patients.
CORONAVIRUS AND THE CORONAVIRUS DISEASE (COVID-19) PANDEMIC
Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses with a ge-
nome size of ;30 kb (1, 2). They are classied into four genera,
a
,
b
,
g
, and
d
, based on
their genomes, and
a
- and
b
-coronaviruses infect mammals (1). In humans, mild upper
respiratory tract infections, such as the common cold, have been reported to be caused
by
a
-coronaviruses (3). However, in the last 2 decades, the world has witnessed three
serious outbreaks of more fatal coronavirus diseases in humans, including COVID-19,
which has become a pandemic of an unprecedented scale that is pushing health care
to its limits worldwide. As of December 2020, over 70 million cases have been reported
globally (https://coronavirus.jhu.edu/map.html). The rst cases of COVID-19 were reported
Citation Kim HS. 2021. Do an altered gut
microbiota and an associated leaky gut affect
COVID-19 severity? mBio 12:e03022-20. https://
doi.org/10.1128/mBio.03022-20.
Editor Maria Gloria Dominguez Bello, Rutgers,
The State University of New Jersey
Copyright © 2021 Kim. This is an open-access
article distributed under the terms of the
Creative Commons Attribution 4.0
International license.
Address correspondence to
hstanleykim@korea.ac.kr.
Published 12 January 2021
January/February 2021 Volume 12 Issue 1 e03022-20 ®mbio.asm.org 1
PERSPECTIVE
Clinical Science and Epidemiology
in 2019 (2).Thisdiseaseiscausedbysevereacuterespiratorysyndromecoronavirus2
(SARS-CoV-2), which is related to the bat origin
b
-coronavirus strain SARS-CoV-1, the
causative agent of the SARS outbreak of 2002. The SARS outbreak lasted for 2 years
and affected 29 countries, resulting in 8,096 cases and 774 deaths (4; https://www.who
.int/publications/m/item/summary-of-probable-sars-cases-with-onset-of-illness-from-1
-november-2002-to-31-july-2003). Another zoonotic coronavirus strain, SARS-CoV, was
the causative agent of the Middle East respiratory syndrome (MERS) outbreak in 2012,
which had spread to 27 countries, with 858 known deaths since then (https://www.who
.int/health-topics/middle-east-respiratory-syndrome-coronavirus-mers#tab=tab_1). Because
SARS-CoV-2 is closely related to these strains, it is also likely to have originated from
bats (5). COVID-19 has affected the world more negatively than either SARS or MERS
because of its high contagiousness, which is estimated to be 2- to 3-fold higher than
that of inuenza (6). The case-fatality rates of COVID-19 vary widely in different coun-
tries, ranging from 1% to 15%; however, the rate typically lies between 2% and 4%
(https://ourworldindata.org/coronavirus).
COVID-19 PATHOGENESIS
SARS-CoV-2 infects primarily the respiratory system and may cause various symp-
toms, ranging from mild illness to signicant hypoxia due to acute respiratory distress
syndrome (7). Common COVID-19 symptoms include fever, cough, myalgia, fatigue,
and pneumonia (2, 7). Diarrhea, nausea, and vomiting have also been reported, indicat-
ing that the gastrointestinal (GI) tract is also a site of infection (812). A substantial pro-
portion of patients appear to have detectable GI symptoms, though this proportion
varies depending on the different patient groups studied (9, 13). A recent modeling
study using large data sets of reported cases suggested that SARS-CoV-2-infected
patients rst develop a fever and then respiratory symptoms, followed by GI tract
symptoms, if they ever occur (14).
The virus uses its spike (S) protein to interact with angiotensin-converting enzyme 2
(ACE2), which is present on the surface of the epithelial cells lining the organs, includ-
ing the lungs and GI tract (10, 1517). Once the virus binds to ACE2, the type 2 trans-
membrane serine protease present in the host cell promotes viral uptake by cleaving
ACE2 and activating the viral S protein, which mediates the entry of the virus into host
cells (16). Next, the viral RNA genome enters the nucleus for replication. Viral reproduc-
tion kills the host cell, ultimately damaging the surrounding tissues as the cell destruc-
tion spreads.
Epithelial cells, alveolar macrophages, and dendritic cells are the main components
of innate immunity in the airway (18). Dendritic cells residing underneath the epithelial
cells and alveolar macrophages are the rst to respond to viruses. Additionally, cellular
damage in the lungs can lead to the release of the cytokines interleukin 8 (IL-8) and IL-
6 by epithelial cells (19). As IL-8 acts as a chemoattractant to recruit neutrophils and T
cells to the infection site, T cell responses are promptly initiated via antigen presenta-
tion by dendritic cells and macrophages. CD4
1
T cells activate B cells to produce virus-
specic antibodies, whereas CD8
1
T cells kill the cells infected by the virus (20). In
most cases, these local immune responses resolve viral infections. However, in some
cases, the immune system is overwhelmed by viral damage. Conversely, the immune
system may trigger a strong inammatory cascade. Thus, in severe COVID-19 patients,
the inltration of numerous immune cells has been observed in the lungs (21), apart
from the increased plasma concentrations of proinammatory cytokines, including IL-
6, IL-1
b
, and tumor necrosis factor alpha (7, 22). This phenomenon of abnormal cyto-
kine overproduction is known as a cytokine storm,and it has been suggested as a
cause of massive inammation and tissue damage in patients, often leading to a seri-
ous outcome (23). However, the existence of this phenomenon in COVID-19 is currently
controversial (24).
Apart from these direct effects, SARS-CoV-2 can indirectly damage the host by in-
hibiting the regular enzymatic function of ACE2 by binding to it. For example, altered
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January/February 2021 Volume 12 Issue 1 e03022-20 mbio.asm.org 2
ACE2 functionality in the lungs may contribute to the pathophysiological process of vi-
rus-induced acute lung injury (25). The expression of ACE2 in gut enterocytes is also an
important regulator of dietary amino acid homeostasis, innate immunity, gut microbial
ecology, and susceptibility to colitis; therefore, its inhibition can cause intestinal inam-
mation (26).
While postmortem examination is invaluable in dissecting details of COVID-19 pathol-
ogy, little has been reported to date. However, it is now clear that diffuse alveolar damage
with capillary congestion and necrosis of pneumocytes, along with various additional fea-
tures, is the major manifestation in the lung (27). Intriguingly, data also showed that
COVID-19 causes extrapulmonary manifestations in various organs, including the GI tract,
liver, kidney, heart, spleen, brain, and bone marrow, with occasional traces of viral infection
(Fig. 1) (2830). Moreover, in an autopsy series of 22 patients focusing on the bodily distri-
bution of SARS-CoV-2, the researchers were able to detect and quantify viral loads in multi-
ple organs, including the lungs, pharynx, heart, liver, brain, and kidneys in most dead
patients (31). The kidneys had the highest viral load among non-respiratory tract organs
examined, even in patients without a history of kidney disease (31). Although more exten-
sivestudiesareneeded,thesendings suggest that extrapulmonary multiorgan dysfunc-
tion may be associated with severe illness in patients with COVID-19, and it is likely caused
by direct exposure to SARS-CoV-2. Consistently, a recent study showed that a high plasma
load of SARS-CoV-2 is associated with increased disease severity and risk of mortality (32).
ALTERED GUT MICROBIOTA MAY LEAD TO SEVERE COVID-19 SYMPTOMS
A substantial proportion of hospitalized patients with respiratory symptoms also
have GI symptoms, such as diarrhea, nausea, and vomiting (812, 33). Furthermore,
seriously affected patients tend to present SARS-CoV-2 in the GI tissues or have GI
symptoms, suggesting that the involvement of this virus in the GI tract increases dis-
ease severity (Fig. 1) (9, 13, 33). Nevertheless, the presence of SARS-CoV-2 in the GI
tract may not always lead to GI symptoms (Fig. 1). For instance, in a study conducted
in Singapore, 50% of the examined COVID-19 patients had a detectable level of virus in
their feces, but only half of them showed GI symptoms, such as diarrhea (34). In a study
of 12 young COVID-19 patients under 18 years of age (3 asymptomatic and 9 with mild
FIG 1 Lines of evidence supporting the hypothesis that a leaky gut affects COVID-19 severity and
further studies that are needed. Current evidence supporting the emerging idea (in the green box)
and evidence directly supporting the hypothesis (in the yellow box) are shown in the blue boxes
with reference numbers. The ideas that are needed to be established through further research to
support the emerging idea and the hypothesis are highlighted in matching green and yellow boxes,
respectively.
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January/February 2021 Volume 12 Issue 1 e03022-20 mbio.asm.org 3
symptoms), the virus was detected in patient feces at higher and longer-lasting levels
than in nasopharyngeal samples (35). In fact, although SARS-CoV-2 is capable of infect-
ing human gut enterocytes when tested on human small intestinal organoids (Fig. 1)
(36), it may differ in an actual healthy gut. This stems from the multiple defense sys-
tems that protect it, including a thick mucus layer (;700
m
m) (37), colonization resist-
ance conferred by the gut microbiome (38), an epithelial layer with tight junctions, and
numerous host factors, such as immunoglobulin A, proteases, and peptides with pro-
tective and antimicrobial functions (37, 39).
Because SARS-CoV-2 can be prevalent in the GI tract regardless of the presence of
symptoms, gut health at the time of infection may be critical for symptom develop-
ment. Elderly patients or those with certain underlying medical conditions, such as
high blood pressure, diabetes, and obesity, are highly vulnerable to the disease (Fig. 1
and 2) (40, 41; https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/
people-at-increased-risk.html). Both elderliness and chronic conditions may be associ-
ated with an altered gut microbiota that affects gut barrier integrity, such that patho-
gens and pathobionts gain more access to the surface of the enterocytes (Fig. 1 and 2)
(38, 39, 4249). Even among younger individuals, who are typically less likely to de-
velop symptomatic COVID-19, patients with obesity or diabetes tend to manifest more
severe symptoms, suggesting that the presence of chronic conditions has a stronger
effect than younger age (Fig. 1) (50). As elderly people are generally patients with
chronic diseases, they can be highly vulnerable to COVID-19 (51).
In a recent study, Gu et al. showed a signicant reduction in bacterial diversity in
gut microbiota samples collected from COVID-19 patients compared with those
obtained from healthy controls (Fig. 1) (52). Additionally, they observed an enrichment
of opportunistic pathogens and depletion in the abundance of benecial bacteria,
including those belonging to the Ruminococcaceae and Lachnospiraceae families. Such
changes in the gut microbiota are generally considered typical signs of dysbiosis and
FIG 2 Model for COVID-19 pathogenesis leading to extrapulmonary complications. Localized infections by SARS-CoV-2
mostly begin in the respiratory system and then progress to the GI tract; they may later develop into a systemic disease,
resulting in multiorgan complications. Disrupted gut barrier integrity associated with elderliness or underlying chronic
conditions, such as hypertension, diabetes, and obesity, may be a crucial effector that allows the virus to gain access to ACE2
on the enterocytes and leak out of the GI tract to spread throughout the body. If SARS-CoV-2 penetrates the gut barrier, it
may cause inammation due to overly reactive immune responses that thereby further increase its leakage from the gut.
Contrastingly, in a healthy GI tract with a higher number of T
reg
cells due to their activation by butyrate, such as in young
healthy children, the virus may be contained in the GI tract and excreted in feces without posing a considerable threat to
the other organs of the body.
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January/February 2021 Volume 12 Issue 1 e03022-20 mbio.asm.org 4
an unhealthy gut (4446). Moreover, the researchers found that inuenza A (H1N1)
infection reduced gut microbiome diversity in patients but resulted in an overall micro-
bial composition different from that in COVID-19 patients (52). In another study, Zuo et
al. reported signicant gut microbiome alterations in COVID-19 patients (53), and they
found an inverse correlation between the abundance of the benecial gut species
Faecalibacterium prausnitzii and disease severity (Fig. 1). Notably, they found the abun-
dance of a few Bacteroides spp., which downregulate the expression of ACE2 in the
murine gut, to be inversely correlated with SARS-CoV-2 load in patient fecal samples
(53). This nding emphasizes the importance of the interrelationship between the gut
microbiome, ACE2 expression, and viral infection. In another study that reported a
strong correlation between COVID-19 risk and an altered gut microbiota (54), Gou et
al. argued that unhealthy gut microbiomes may be the underlying reason for the pre-
disposition of normal individuals to severe COVID-19 (54).
Notably, these studies demonstrating a close link between gut microbiota dysbiosis
and COVID-19 severity have reported a common nding (5254). Benecial bacteria,
whose abundance was reduced in COVID-19 patients, were reported to belong to the
families Ruminococcaceae or Lachnospiraceae (52), a single species F. prausnitzii (53),
and the class Clostridia (54). The class Clostridia includes the family Ruminococcaceae,
which includes the species F. prausnitzii, which is one of the major butyric acid-produc-
ing bacteria in the gut (55). While the benecial impact of F. prausnitzii on human
health is well established (56), a subspecies that causes a predisposition to atopic der-
matitis in infants and young children by competing with the benecial members of the
species has been identied (57). The intricate microbial interactions and the physiology
involving this important butyrate-producing species warrant future investigations to
understand its inuence on human health and disease (57, 58).
Butyric acid, produced by many benecial gut bacteria belonging to Clostridia,isa
short-chain fatty acid (SCFA), which, along with propionic and acetic acids, is a fermen-
tation product of dietary ber that plays a pivotal role in gut health (Fig. 2). It helps
maintain gut barrier integrity by serving as an important energy source for colono-
cytes, inhibiting the activation of NF-κB, activating the G protein-coupled receptor pair
of GPR41 and GPR43, inhibiting histone deacetylase activity, which causes anti-inam-
matory activities, and promoting regulatory T cells (T
reg
) cells (5964). T
reg
cells have a
central role in the suppression of inammatory and allergic responses (Fig. 2) (59).
Depletion of certain butyric acid producers in the gut microbiota has been identied in
a few chronic diseases, including allergies, inammatory diseases, colorectal cancer,
and Crohns disease (56, 57, 65).
DISRUPTED GUT BARRIER INTEGRITY MAY BE ATTRIBUTABLE TO EXTRAPULMONARY
COMPLICATIONS, INCLUDING HEART, LIVER, KIDNEY, AND BRAIN DYSFUNCTION
Along with having respiratory and GI symptoms, COVID-19 patients often manifest
other symptoms, such as headache and hepatic, pancreatic, and cardiac dysfunction
(66). This coincides with the fact that ACE2, the receptor for SARS-CoV-2, is expressed
not only in the lungs and the GI tract but also in various other organs, including the
liver, heart, kidneys, bladder, and brain (19, 25, 29). Since ACE2 regulates vital proc-
esses, such as normal cardiac function (e.g., blood pressure control), optimal beta-cell
function, and insulin sensitivity (25), if these organs are damaged or their essential
ACE2 functions are blocked by the virus, various complications may occur (67).
Histopathological evidence for viral infection and/or actual viral components has been
observed in various internal organs in biopsy samples from severely ill patients or from
autopsy specimens (2831).
Thus, it is important to determine how SARS-CoV-2 reaches internal organs other
than the lungs or GI tract. Altered gut microbiotas, which may be associated with eld-
erliness and certain underlying medical conditions that predispose COVID-19 patients
to severe symptoms, often lead to disrupted gut barrier integrity (Fig. 1 and 2) (4249).
While a link between patients with severe illness, gut symptoms (e.g., diarrhea), and a
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January/February 2021 Volume 12 Issue 1 e03022-20 mbio.asm.org 5
leaky gut still needs to be established (Fig. 1), it is highly likely to be the case because
patients with diarrhea present increased levels of systemic IL-6 and fecal calprotectin,
which are indicators of gut inammation and disrupted gut integrity, such as a thinned
mucus layer and reduced tight junctions between enterocytes (Fig. 2) (68). Drastically
elevated plasma IL-6 concentrations have been associated with the presence of SARS-
CoV-2 RNA in the plasma of critically ill patients (32, 69). It is therefore plausible that
critically ill COVID-19 patients may have a disrupted gut barrier, also known as a leaky
gut(4749, 70), which may allow SARS-CoV-2 to not only bind to ACE2 on the entero-
cytes but also exit the GI tract and enter the bloodstream, allowing it to access various
organs expressing ACE2 throughout the body (Fig. 2). If SARS-CoV-2 penetrates the gut
barrier, it may cause inammation due to overly reactive immune responses, thereby
further increasing gut leakage (Fig. 2) (59). Contrastingly, in a healthy GI tract with a
high number of T
reg
cells that are activated by butyrate, such a proinammatory
response may be blocked (59). However, a link between a leaky gut, plasma viral load,
and extrapulmonary multiorgan dysfunction remains to be established (Fig. 1).
CONCLUSIONS AND PERSPECTIVES
A strong pattern has emerged from patients with severe COVID-19, as many of
them are either elderly or have certain underlying medical conditions which may be
associated with an altered gut microbiota (38, 39, 4249). Such dysbiosis of the gut
microbiota may be associated with disrupted gut barrier integrity, which may allow
SARS-CoV-2 to gain access to the otherwise well-protected enterocytes and to circulate
and infect internal organs expressing ACE2 (Fig. 2). If this is what is happening in the
serious cases of this illness that present extrapulmonary multiorgan dysfunction, test-
ing for a leaky gut and fecal and plasma viral loads will be of high value for a more
accurate prognosis, particularly for those likely to have altered gut microbiotas (Fig. 3).
FIG 3 Exploiting the gut microbiota for better COVID-19 disease prevention and management. Testing for leaky gut and
fecal and plasma viral loads may be used to improve diagnoses for seriously ill patients and for establishing a basis for
transmission precautions from some patients who may have prolonged fecal shedding of the virus even after viral
clearance in the respiratory tract. This presents the intriguing, but presently unsubstantiated, possibility that an inamed
leaky gut, which may be associated with a higher risk of severe illness, may be improved or treated via a few
interventions. FMT, production of next-generation probiotics focusing on butyrate-producing gut microbes, or simply
increasing the daily intake of dietary ber may be considered in improving the gut health of COVID-19 patients.
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January/February 2021 Volume 12 Issue 1 e03022-20 mbio.asm.org 6
Furthermore, fecal viral load data can also be useful for informing transmission precau-
tions, because some patients may have prolonged fecal shedding of the virus even af-
ter viral clearance in the respiratory tract (Fig. 3) (33, 35).
While developing treatments and vaccines for COVID-19 is of prime signicance,
exploiting the gut microbiota to improve disease prevention and management may
also be important (Fig. 3). The rst treatment to be considered for the seriously ill may
be fecal microbiota transplantation (FMT). This practice enables stool infusion from a
healthy individual to a patient with presumed gut microbial dysbiosis (71). FMT has
been remarkably successful in the treatment of Clostridioides difcile infection (CDI)
(72). Although FMT has shown only marginal success in treating other conditions, such
as inammatory bowel disease and metabolic disorders, COVID-19 may not be the
same because, unlike these inammatory disorders, it is an infectious disease as CDI,
which has a clear and simpler therapeutic target. However, in any case, safety issues
associated with carrying over undetected additional potential pathogens need to be
seriously considered before FMT can be explored in the context of COVID-19 (72). The
development of next-generation probiotics focusing on butyrate-producing gut
microbes can also be pursued (73). However, these novel microbial therapeutics still
need to overcome the hurdles of the regulatory framework (73). Lastly, simply increas-
ing the daily intake of dietary ber may markedly help improve gut health (74), as ber
is directly utilized by benecial gut microbes to produce SCFAs, with butyrate being a
key substance (74). This dietary adaptation may be the most easy and effective method
that can be considered to be implemented immediately to prevent severe COVID-19 or
just for general health improvement.
ACKNOWLEDGMENTS
This work was supported by grants NRF-2018R1A2B2006456, 2018M3A9F3055923,
and 2015M3C9A4053393 from the National Research Foundation (NRF) of the Republic
of Korea.
I declare no competing interests.
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... 24,25 Also, poor outcome were reported in elderly or comorbid patients. 26,27 Recently, several studies discussed the factors associated with the dysbiosis in COVID-19 patients manifesting GI symptoms. According to some research, increased inflammation may lead to a "leaky gut," which permit the transfer of bacterial metabolites and toxins into the systemic circulation. ...
... According to some research, increased inflammation may lead to a "leaky gut," which permit the transfer of bacterial metabolites and toxins into the systemic circulation. 27 This might cause further complications to the severe COVID-19 patients. 24 Besides, interventions targeting to re-establish a correct microbiota composition are important for developing a more comprehensive approach to managing COVID-19. ...
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Background and aims: Alteration in humans' gut microbiota was reported in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The gut and upper respiratory tract (URT) microbiota harbor a dynamic and complex population of microorganisms and have strong interaction with host immune system homeostasis. However, our knowledge about microbiota and its association with SARS-CoV-2 is still limited. We aimed to systematically review the effects of gut microbiota on the SARS-CoV-2 infection and its severity and the impact that SARS-CoV-2 could have on the gut microbiota. Methods: We searched the keywords in the online databases of Web of Science, Scopus, PubMed, and Cochrane on December 31, 2021. After duplicate removal, we performed the screening process in two stages; title/abstract and then full-text screening. The data of the eligible studies were extracted into a pre-designed word table. This study adhered to the PRISMA checklist and Newcastle-Ottawa Scale Bias Assessment tool. Results: Sixty-three publications were included in this review. Our study shows that among COVID-19 patients, particularly moderate to severe cases, the gut and lung microbiota was different compared to healthy individuals. In addition, the severity, and viral load of COVID-19 disease would probably also be influenced by the gut, and lung microbiota's composition. Conclusion: Our study concludes that there was a significant difference in the composition of the URT, and gut microbiota in COVID-19 patients compared to the general healthy individuals, with an increase in opportunistic pathogens. Further, research is needed to investigate the probable bidirectional association of COVID-19 and human microbiome.
... La microbiota es el conjunto de microorganismos (bacterias, virus, hongos, arqueas, protistas) que habitan nuestro cuerpo y se encuentran en relación simbiótica con él. La ruptura de dicho equilibrio (disbiosis) se asocia con enfermedades y cambios en la composición taxonómica, diversidad y función de la microbiota intestinal causando malestares (diarrea, estreñimiento, obesidad, etc.) 26,27 . ...
... Dichas condiciones propician un medio inflamatorio disbiótico que induce la expresión de ECA-2, aumentando la replicación del SARS-CoV-2 en el TGI y la diseminación a otros sitios. La ECA-2 captura aminoácidos de la dieta, regula la expresión de péptidos antimicrobianos (inmunidad innata) y es un regulador Antiinflamación del microbioma intestinal y la inmunidad 26,27 . Se vio que existen interacciones bidireccionales de la mucosa respiratoria y la microbiota intestinal, conocidas como eje intestino-pulmón. ...
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Introducción: Un nuevo brote de coronavirus surgió en 2019 en Wuhan, China, causando conmoción en el sistema sanitario de todo el mundo; el Comité Internacional de Taxonomía de Virus lo denominó SARS-CoV-2, agente causante de la enfermedad COVID-19. El espectro de gravedad de la enfermedad es muy amplio: la mayoría de los pacientes no presentan gravedad, pero otros pueden desarrollar neumonías, y la insuficiencia respiratoria aguda es la causa más frecuente de mortalidad. Objetivo: analizar y desarrollar las distintas alternativas terapéuticas aportadas por la Biotecnología para tratar los síntomas de aquellos pacientes con COVID-19. Metodología: se realizó una revisión de la bibliografía disponible, a partir de enero de 2020 en PubMed, acerca de los tratamientos que se encuentran aún en ensayos clínicos y aquellos que cuentan con aprobación bajo uso de emergencia para la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a políticas de salud establecidas para la terapéutica durante dicha pandemia. Resultados: este trabajo aborda las nuevas alternativas terapéuticas para COVID-19 derivadas de la Biotecnología, que se encuentran tanto en uso como en etapas de ensayos clínicos comprendidos dentro del segmento de los biofármacos y las bioterapias. Se incluye un breve resumen del estatus regulatorio de entidades de salud, el mecanismo de acción de dichas terapias y características generales de cada uno. Se incluyen novedosas bioterapias que se empezaron a implementar para afrontar la pandemia. Conclusiones: la pandemia de coronavirus está poniendo a prueba el sistema sanitario internacional, para brindar soluciones tanto desde el diagnóstico y prevención como para el tratamiento de la población a fin de disminuir la mortalidad. Esto incluyó, obviamente también, al área de la Biotecnología aplicada a la salud, que ha aportado en los tres aspectos mencionados; el presente trabajo se centra en las respuestas de tipo terapéutico que ha brindado y que están comercializadas o en fases clínicas.
... Значний вклад у вивчення зазначеної проблеми зробили (Schweinburg F. B.etal., 1949;Deitch E. A.etal., 1985;Bäckhed F. etal., 2005;Devillard E. etal., 2009;Adler C. J.etal., 2013;Clarke S. F.etal., 2014;Conlon M. A.etal., 2014;Bermon S. etal., 2015) та інші. У дослідженнях та публікаціях за останні п'ять роківпроблему впливу фізичного навантаження на мікробіоту та деякі регуляторні механізми вивчали: через призму окислювального стресу, проникності кишківника, електролітного дисбалансу (Donati Zeppa etal., 2019); чутливості до інсуліну (Fjaere etal., 2019); прозапального профілю (Zhao etal., 2018); окисного стресу (Donati Zeppaetal., 2019); термального шоку (Kuibidaetal., 2022;Kuibidaetal., 2022); механізму впливу мікробіоти (Cataldi etal., 2022); особливостей використання лактату (Scheiman etal., 2019); утворення пропіонату грамнегативними мікроорганізмами (Scheiman etal., 2019); негерметичності кишківника (Kim, 2021); дисбактеріозу (Yeoh etal., 2021) та ін. ...
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Мікробіота людини ‒ важливий чинник для покращення стану здоров’я і спортивних результатів. На сьогодні механізм впливу фізичної активності та існуючих дієт на мікроорганізми людей і тварин не з’ясовано, що й стало метою цього оглядового дослідження. Застосовано метод дослідження, який ґрунтується на використанні ключових слів для пошуку наукових джерел в електронних базах даних PubMed та SPORTD iscus. Встановлено, що механізм впливу мікробіоти включає взаємопов’язані чинники та шляхи: 1) активацію гіпоталамічно-гіпофізарно-надниркової осі та біосинтез гормонів, ферментів, вітамінів, імуномодуляторів, факторів росту фібробластів, антибіотиків; 2) вплив на центральну та ентеральну нервові системи; 3) пригнічення сигнальних шляхів рецептора TLR4, який задіяний в імунній та запальній відповіді; 4) підвищення біосинтезу кишкового імуноглобуліну А та резистентності до колонізації специфічними коменсальними мікроорганізмами; 5) зміну профілю жовчних кислот, які мають антимікробну функцію і здійснюють селективний тиск на певні штами бактерій; 6) прискорення процесу утворення коротколанцюгових жирних кислот (ацетату, пропіонату, бутирату), виникнення ефекту знеболення та зниження рівня ліпополісахаридів крові; 7) інтенсифікацію життєдіяльності грамнегативних мікроорганізмів Veillonella, які перетворюють лактат в бутират, важливого для синтезу муцину, енергозабезпечення колоноцитів, захисту кишкового епітелію, енергозабезпечення та зростання витривалості; 8) підтримку глікемічного гомеостазу; 9) утилізацію кетокислот та активних форм кисню; 10) зміну бар’єрної функції та проникності кишківника; 11) посилення транслокації бактерій із товстої кишки в кровоносні та лімфатичні шляхи; 12) вивільнення міокінів з клітин м’язових волокон; 13) скорочення часу проходження харчових мас через кишківник; 14) поглинання поживних речовин; 15) стійкість до колонізації патогенів; 16) зміни стану гідратації тощо. Мікробіоту можна модифікувати короткочасними змінами дієти, але зміни зберігаються лише протягом кількох днів. Дієти з малою кількістю клітковини й багаті очищеними вуглеводами та жирами викликають зменшення різноманітності та активності спільноти мікроорганізмів. При ферментації не перетравних вуглеводів утворюються солі та ефіри органічних кислот: ацетат, пропіонат і бутират; гази H2 і CO2; аміак; аміни; феноли та енергія, яку бактерії використовують для росту та підтримки клітинної функції.
... Therefore, it is essential for clinicians to avoid prescribing antibiotics to patients seeking treatment for COVID-19 in the absence of an additional indication. Recent studies suggest that patients with altered gut microbiota might experience more severe COVID-19 symptoms [153]. Antibiotics may alter digestive microbial flora further, so empiric treatment for bacterial pneumonia in COVID-19 patients should only be initiated when clinical suspicion is high. ...
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Over the last few years, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) unleashed a global public health catastrophe that had a substantial influence on human physical and mental health, the global economy, and socio-political dynamics. SARS-CoV-2 is a respiratory pathogen and the cause of ongoing COVID-19 pandemic, which testified how unprepared humans are for pandemics. Scientists and policymakers continue to face challenges in developing ideal therapeutic agents and vaccines, while at the same time deciphering the pathology and immunology of SARS-CoV-2. Challenges in the early part of the pandemic included the rapid development of diagnostic assays, vaccines, and therapeutic agents. The ongoing transmission of COVID-19 is coupled with the emergence of viral variants that differ in their transmission efficiency, virulence, and vaccine susceptibility, thus complicating the spread of the pandemic. Our understanding of how the human immune system responds to these viruses as well as the patient groups (such as the elderly and immunocompromised individuals) who are often more susceptible to serious illness have both been aided by this epidemic. COVID-19 causes different symptoms to occur at different stages of infection, making it difficult to determine distinct treatment regimens employed for the various clinical phases of the disease. Unsurprisingly, determining the efficacy of currently available medications and developing novel therapeutic strategies have been a process of trial and error. The global scientific community collaborated to research and develop vaccines at a neck-breaking speed. This review summarises the overall picture of the COVID-19 pandemic, different mutations in SARS-CoV-2, immune response, and the treatment modalities against SARS-CoV-2.
... The human host ACE2 cell surface receptors in the cell membrane of epithelial tissue bind with the S2 domain after being cleaved by transmembrane serine protease 2 (TMPRSS2) in which proteolysis of S1 subunit from the S2 subunit occurs and initiates binding to the ACE2 receptor in which the pathogen enters inside the host cell [30]. The pathogen on intruding the host cell initiates the replication phase for reproduction and damages the epithelial tissue leading to cause severe infection [34]. As this predominant ACE2 receptor of the human epithelial tissue of the intestine and lungs has an affinity towards binding SARS-CoV-2, it is more likely to cause infection in the pulmonary and gastrointestinal systems [32]. ...
Article
The coronavirus pandemic hit the world with different variants of SARS-CoV-2; reliable therapeutics are needed every hour to control and minimize the infection. To date, the way to menace the chaos of post-Covid infection is not confined rationally. Researchers are still on their way to the progression of an efficient way to eradicate the disease. However, to prevent it from causing infection post-entry into the body, there have been a few strategies to maintain and boost the immune system. At the onset of infection when no antiviral therapeutics were available, convalescent plasma therapies as a proposed mechanism were adapted to treat the post-Covid infection. Researchers have formulated the administration of different types of vaccines based on attenuated or inactivated nucleic acids or subunits after approval from the FDA and still continue to find the best reliable vaccines for better enhancement in inducing immunogenicity of the immune system to fight against the disease. The covid-19 infection affects the gut and lung axis and there has been dysbiosis of microbiota which leads to cause secondary infections. To accomplish homeostasis of essential microbiota in the body, the administration of different strains of probiotic bacteria has been one way to induce immunogenicity and combat the disease.
... In COVID-19 patients, the numbers of Lactobacillus, Bifidobacterium, Eubacterium rectale, and Faecalibacterium prausnitzii in the intestines decrease, whereas the number of conditionally pathogenic bacteria such as Enterococcus increases. The degree of imbalance in intestinal flora is positively correlated with disease severity, suggesting that the gastrointestinal tract may be one of the target organs of SARS-CoV-2 [19] . A study by Tang et al. [20] reported an imbalance of gut flora is observed in COVID-19 patients, and the dynamic changes in the flora are related to the disease severity and hematological parameters. ...
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Respiratory symptoms are most commonly experienced by patients in the early stages of novel coronavirus disease 2019 (COVID-19). However, with a better understanding of COVID-19, gastrointestinal symptoms such as diarrhea, nausea, and vomiting have attracted increasing attention. The gastrointestinal tract may be a target organ of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The intestinal microecological balance is a crucial factor for homeostasis, including immunity and inflammation, which are closely related to COVID-19. Herbal medicine can restore intestinal function and regulate the gut flora structure. Herbal medicine has a long history of treating lung diseases from the perspective of the intestine, which is called the gut–lung axis. The physiological activities of guts and lungs influence each other through intestinal flora, microflora metabolites, and mucosal immunity. Microecological modulators are included in the diagnosis and treatment protocols for COVID-19. In this review, we demonstrate the relationship between COVID-19 and the gut, gut–lung axis, and the role of herbal medicine in treating respiratory diseases originating from the intestinal tract. It is expected that the significance of herbal medicine in treating respiratory diseases from the perspective of the intestinal tract could lead to new ideas and methods for treatment. http://links.lww.com/AHM/A33.
... From this collection, seven species transmitted to humans have been discovered so far, which cause diseases such as colds in humans [1]. Coronaviruses often attack the respiratory tract and sometimes show symptoms in the intestines and stomach [2,3]. Coronaviruses usually first infect the mucous membranes of the respiratory tract in the throat and nose, causing symptoms similar to the common cold [4]. ...
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Evaluated efficacy of Respiratory Physiotherapy and Remdesivir on patients with COVID-19 pneumonia. In current systematic review and meta-analysis study, articles published January 2019 to December 1, 2021 were reviewed in the databases of PubMed, Scopus, Web of Science, and EBSCO. Risk ratio and mean differences with 95% confidence interval (CI), fixed effect model and Mantel-Haenszel or Inverse-variance formula were calculated. The Meta analysis have been evaluated with the statistical software Stata/MP v.16 (The fastest version of Stata). Mean differences of PaO2/FiO2 ratio at 6h after chest Respiratory Physiotherapy was (MD, 66 mmHg 95 % CI 64.71 mmHg, 67.28 mmHg; p=0.0007). Risk ratio of recovery rate between experimental and control group was 0.20 (RR, 0.20 95 % CI 0.15, 0.25) with high heterogeneity (I2 =78.84%; p=0.00). Risk ratio of mortality rate between experimental and control group was-0.34 (RR,-0.34 95 % CI-0.65,-0.03) with low heterogeneity (I2<0%; p=0.51). Based on the findings of meta-analysis, Respiratory Physiotherapy can play an effective role in respiratory therapy and rehabilitation of patients admitted to the ICU with COVID-19. A meta-analysis showed that treatment with Remdesivir could increase the recovery rate, especially in the early days of COVID-19; also reduces the mortality rate.
... Ancak hastalığın seyri sırasında karaciğer ve bağırsak gibi organlarda işlev bozukluğu gelişimi veya çoklu organ yetmezliği bildirilmiştir (Chen ve ark., 2020;D'Amico ve ark., 2020;Feng ve ark., 2020;Pan ve ark., 2020;Wang ve ark., 2020). Artan kanıtlar, COVID-19'un yalnızca solunum sisteminde değil, aynı zamanda hastaların gastrointestinal sistem (GIS) yolunda (dışkı ve rektal sürüntüler) da tespit edildiğini göstermektedir (Gu ve ark., 2020;Kim, 2021). Singapur'da yapılan bir çalışmada, COVID-19 enfeksiyonu pozitif olan hastaların %50'sinin dışkılarında virüs tespit edilmiştir ve bu hasta kohortunda, solunum numunelerinin virüs RNA'sı için negatif olarak test edilmesinden sonra dışkı numunelerinin yaklaşık 5 hafta boyunca COVID-19 pozitif kaldığı gözlemlenmiştir (Wu ve ark., 2020). ...
... Our observation of elevated anti-gut microbial IgA antibodies supports the evidence for gut barrier dysfunction in severe COVID-19 25,26 that may necessitate containment of gut microbiota translocated to the circulation and CSF 27 . In that regard, underlying conditions for microbiota dysbiosis, such as increased age, hypertension and diabetes have been observed in our class III cohort (Table 1). ...
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Growing evidence suggests that coronavirus disease 2019 (COVID-19) is associated with acute and long-term neurological sequelae. However, the underlying pathophysiological mechanisms resulting in central nervous system (CNS) derogation remain unclear, posing both diagnostic and therapeutic challenges. Here, we performed a cross-sectional study (NCT04472013) and multidimensional characterization of cerebrospinal fluid (CSF) and plasma-targeted proteomics in different Neuro-COVID severity classes with corresponding clinical and imaging data. COVID-19 patients displayed a plasma cytokine storm but a non-inflammatory CSF profile. Severely affected patients displayed signs of blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self- and non-self antigens. Also, COVID-19 patients had decreased regional brain volumes associated with specific CSF and plasma parameters. We provide a multiparametric framework of Neuro-COVID severity classifiers. Collectively, this data identified several potentially actionable targets that may be addressed to prevent COVID-19-related neurological sequelae.
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In Dec. 2019‐January 2020, a pneumonia illness originating in Wuhan, China, designated as coronavirus disease 2019 (COVID‐19) was shown to be caused by a novel RNA coronavirus designated as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). People with advanced age, male sex, and/or underlying health conditions (obesity, type 2 diabetes, cardiovascular disease, hypertension, chronic kidney disease, and chronic lung disease) are especially vulnerable to severe COVID‐19 symptoms and death. These risk factors impact the immune system and are also associated with poor health, chronic illness, and shortened longevity. However, a large percent of patients without these known risk factors also develops severe COVID‐19 disease that can result in death. Thus, there must exist risk factors that promote exaggerated inflammatory and immune response to the SARS‐CoV‐2 virus leading to death. One such risk factor may be alcohol misuse and alcohol use disorder because these can exacerbate viral lung infections like SARS, influenza, and pneumonia. Thus, it is highly plausible that alcohol misuse is a risk factor for either increased infection rate when individuals are exposed to SARS‐CoV‐2 virus and/or more severe COVID‐19 in infected patients. Alcohol use is a well‐known risk factor for lung diseases and ARDS in SARS patients. We propose that alcohol has three key pathogenic elements in common with other COVID‐19 severity risk factors: namely, inflammatory microbiota dysbiosis, leaky gut, and systemic activation of the NLRP3 inflammasome. We also propose that these three elements represent targets for therapy for severe COVID‐19.
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Objective: To estimate the infection fatality risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on deaths with confirmed coronavirus disease 2019 (covid-19) and excess deaths from all causes. Design: Nationwide seroepidemiological study. Setting: First wave of covid-19 pandemic in Spain. Participants: Community dwelling individuals of all ages. Main outcome measures: The main outcome measure was overall, and age and sex specific, infection fatality risk for SARS-CoV-2 (the number of covid-19 deaths and excess deaths divided by the estimated number of SARS-CoV-2 infections) in the community dwelling Spanish population. Deaths with laboratory confirmed covid-19 were obtained from the National Epidemiological Surveillance Network (RENAVE) and excess all cause deaths from the Monitoring Mortality System (MoMo), up to 15 July 2020. SARS-CoV-2 infections in Spain were derived from the estimated seroprevalence by a chemiluminescent microparticle immunoassay for IgG antibodies in 61 098 participants in the ENE-COVID nationwide seroepidemiological survey between 27 April and 22 June 2020. Results: The overall infection fatality risk was 0.8% (19 228 of 2.3 million infected individuals, 95% confidence interval 0.8% to 0.9%) for confirmed covid-19 deaths and 1.1% (24 778 of 2.3 million infected individuals, 1.0% to 1.2%) for excess deaths. The infection fatality risk was 1.1% (95% confidence interval 1.0% to 1.2%) to 1.4% (1.3% to 1.5%) in men and 0.6% (0.5% to 0.6%) to 0.8% (0.7% to 0.8%) in women. The infection fatality risk increased sharply after age 50, ranging from 11.6% (8.1% to 16.5%) to 16.4% (11.4% to 23.2%) in men aged 80 or more and from 4.6% (3.4% to 6.3%) to 6.5% (4.7% to 8.8%) in women aged 80 or more. Conclusion: The increase in SARS-CoV-2 infection fatality risk after age 50 appeared to be more noticeable in men than in women. Based on the results of this study, fatality from covid-19 was greater than that reported for other common respiratory diseases, such as seasonal influenza.
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The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored. In this study, Massachusetts Consortium for Pathogen Readiness (MassCPR) investigators assess the relationship between SARS-CoV-2 viral load and COVID-19 disease severity and report that the levels of detectable viral RNA, especially in plasma, correlates with severity of respiratory disease, inflammatory markers and predicted risk of death.
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COVID-19 is a pandemic viral disease with catastrophic global impact. This disease is more contagious than influenza such that cluster outbreaks occur frequently. If patients with symptoms quickly underwent testing and contact tracing, these outbreaks could be contained. Unfortunately, COVID-19 patients have symptoms similar to other common illnesses. Here, we hypothesize the order of symptom occurrence could help patients and medical professionals more quickly distinguish COVID-19 from other respiratory diseases, yet such essential information is largely unavailable. To this end, we apply a Markov Process to a graded partially ordered set based on clinical observations of COVID-19 cases to ascertain the most likely order of discernible symptoms (i.e., fever, cough, nausea/vomiting, and diarrhea) in COVID-19 patients. We then compared the progression of these symptoms in COVID-19 to other respiratory diseases, such as influenza, SARS, and MERS, to observe if the diseases present differently. Our model predicts that influenza initiates with cough, whereas COVID-19 like other coronavirus-related diseases initiates with fever. However, COVID-19 differs from SARS and MERS in the order of gastrointestinal symptoms. Our results support the notion that fever should be used to screen for entry into facilities as regions begin to reopen after the outbreak of Spring 2020. Additionally, our findings suggest that good clinical practice should involve recording the order of symptom occurrence in COVID-19 and other diseases. If such a systemic clinical practice had been standard since ancient diseases, perhaps the transition from local outbreak to pandemic could have been avoided.
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Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.
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The outbreak of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has been recently declared a pandemic by the World Health Organization. In addition to its acute respiratory manifestations, SARS‐CoV‐2 may also adversely affect other organ systems. To date, however, there is very limited understanding of the extent and management of COVID‐19‐related conditions outside of the pulmonary system. This narrative review provides an overview of the current literature about the extra‐pulmonary manifestations of COVID‐19 that may affect the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. This review also describes current understanding of the extra‐pulmonary complications caused by COVID‐19 in order to improve the management and prognosis of patients with COVID‐19. This article is protected by copyright. All rights reserved.
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The novel coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), first appeared in December 2019, in Wuhan, China and evolved into a pandemic. As Angiotensin-Converting Enzyme 2 (ACE2) is one of the potential target receptors for SARS-CoV-2 in human body, which is expressed in different tissues, multiple organs might become affected. In the initial phase of the current pandemic, a handful of post-mortem case-series revealed COVID-19-related pathological changes in various organs. Although pathological examination is not a feasible method of diagnosis, it can elucidate pathological changes, pathogenesis of the disease, and the cause of death in COVID-19 cases. Herein, we thoroughly reviewed multiple organs including lung, gastrointestinal tract, liver, kidney, skin, heart, blood, spleen, lymph nodes, brain, blood vessels, and placenta in terms of COVID-19-related pathological alterations. Also, these findings were compared with SARS and MERS infection, wherever applicable. We found a diverse range of pathological changes, some of which resemble those found in SARS and MERS.
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The intestinal epithelium serves as a dynamic barrier to the environment and integrates a variety of signals, including those from metabolites, commensal microbiota, immune responses and stressors upon ageing. The intestine is constantly challenged and requires a high renewal rate to replace damaged cells in order to maintain its barrier function. Essential for its renewal capacity are intestinal stem cells, which constantly give rise to progenitor cells that differentiate into the multiple cell types present in the epithelium. Here, we review the current state of research of how metabolism and ageing control intestinal stem cell function and epithelial homeostasis. We focus on recent insights gained from model organisms that indicate how changes in metabolic signalling during ageing are a major driver for the loss of stem cell plasticity and epithelial homeostasis, ultimately affecting the resilience of an organism and limiting its lifespan. We compare findings made in mouse and Drosophila and discuss differences and commonalities in the underlying signalling pathways and mechanisms in the context of ageing.
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Background: Descriptions of the pathological features of COronaVIrus Disease-2019 (COVID-19) caused by the novel zoonotic pathogen Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) emanate from tissue biopsies, case reports and small post-mortem studies restricted to the lung and specific organs. Whole body autopsy studies of COVID-19 patients have been sparse. To further define the pathology caused by SARS-CoV-2 across all body organs in both individuals with and without co-morbidities Italian patients who died of COVID-19. Methods: We performed autopsies on 22 patients with COVID-19 (18 with co-morbidities and 4 without co-morbidities) who died at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy. Tissues from the lung, heart, liver, kidney, spleen and bone marrow (but not the brain) were examined. Only lung tissues were subject to transmission electron microscopy. Results: COVID-19 causes multisystem pathology. Pulmonary and cardiovascular involvement are dominant pathological features. Extra-pulmonary manifestations include hepatic, kidney, splenic and bone marrow involvement, and microvascular injury and thrombosis were also detected. These findings were similar in patients with or without pre-existing medical co-morbidities. Conclusions: SARS-CoV-2 infection causes multisystem disease and significant pathology in most organs in patients with and without co-morbidities.