Invest Clin 62(Suppl. 2): 58 - 68, 2021 https://doi.org/10.22209/IC.v62s2a05
Corresponding author: Leonor Chacín-Bonilla. Instituto de Investigaciones Clínicas “Dr. Américo Negrette”, Fa-
cultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela. E-mail: leonorbonilla42@yahoo.com
SARS-CoV-2: Potential feco-oral transmission
and implications on the spread and severity
of COVID-19 in Venezuela. Mini-review.
Leonor Chacín-Bonilla
1
and Nathalie Chacón
2
1
Instituto de Investigaciones Clínicas “Dr. Américo Negrette”, Facultad de Medicina,
Universidad del Zulia, Maracaibo, Venezuela.
2
Department of Public Health, School of Medicine, University of Texas Rio Grande Valley,
Edinburg, TX, USA.
Key words: SARS-CoV-2; COVID-19; transmission; Venezuela.
Abstract. The recognized human-to-human transmission of SARS-CoV-2 is
through respiratory droplets and contact with contaminated surfaces. However,
the high transmissibility of the virus and the pattern of symptoms of COVID-19
suggest the likelihood of other forms of spread. Increasing evidence suggests
that SARS‐CoV‐2 could be transmitted by the feco‐oral route. SARS-CoV-2 is
known to infect gastrointestinal epithelial cells and a significant number of
infected people have gastrointestinal symptoms. Viable viruses, viral RNA, and
prolonged shedding of viral RNA have been detected in the feces of COVID-19
patients. The virus has been found in sewage and surface waters of several coun-
tries. The possible feco-oral transmission of SARS-CoV-2 could be significant in
low-income countries. High poverty levels and the collapse of health and other
public services might increase the risk of Venezuelans to suffer a more devastat-
ing impact from COVID-19 than other populations. In conclusion, the feco-oral
transmission of SARS-CoV-2 has not been demonstrated. However, it is conceiv-
able and the impact of COVID-19 could be high in low-income countries, espe-
cially in Venezuela due to its humanitarian crisis. The lack of information on
the viability and infectivity of the virus in wastewaters and surface waters and
the risk of transmission of the infection are important gaps in knowledge that
deserve further investigation.
Potential feco-oral spread of SARS-CoV-2 and implications for Venezuela 59
Vol. 62(Suppl. 2): 58 - 68, 2021
SARS-CoV-2: Potencial transmisión feco-oral e implicaciones
en la propagación y gravedad del COVID-19 en Venezuela.
Mini-revisión.
Invest Clin 2021; 62 (Suppl. 2): 58-68
Palabras clave: SARS-CoV-2; COVID-19; transmisión; Venezuela.
Resumen. La transmisión reconocida del SARS-CoV-2 de persona a perso-
na es a través de gotitas respiratorias y contacto con superficies contaminadas.
Sin embargo, la gran transmisibilidad del virus y el modelo de síntomas del
COVID-19 hacen pensar en la probabilidad de otras formas de propagación. Evi-
dencias crecientes sugieren que SARS-CoV-2 podría transmitirse por vía feco-
oral. Se sabe que SARS-CoV-2 infecta las células epiteliales gastrointestinales y
un número significativo de personas infectadas tienen síntomas gastrointesti-
nales. En las heces de pacientes con COVID-19, se han detectado virus viables,
ARN viral y la eliminación prolongada de ARN viral. Se ha detectado el virus
en las aguas residuales y superficiales de varios países. La posible transmisión
feco-oral del SARS-CoV-2 podría ser significativa en países de bajos ingresos.
Los altos niveles de pobreza y el colapso del sistema de salud y de otros servi-
cios públicos podrían aumentar el riesgo de los venezolanos de sufrir un im-
pacto más devastador de la COVID-19 que otras poblaciones. En conclusión,
la transmisión feco-oral de SARS-CoV-2 no se ha demostrado. Sin embargo,
es concebible y el impacto de la COVID-19 podría ser alto en países de bajos
ingresos, especialmente en Venezuela debido a su crisis humanitaria. La falta
de información sobre la viabilidad e infectividad del virus en aguas residuales y
superficiales y el riesgo de transmisión de la infección son brechas importantes
en el conocimiento que necesitan una mayor investigación.
Received: 21-03-2021 Accepted: 01-07-2021
INTRODUCTION
The novel Severe Acute Respiratory Syn-
drome Coronavirus 2 (SARS-CoV-2) leading
to Coronavirus Disease 2019 (COVID-19),
first appeared in Wuhan, China (1) and hea-
ded to a pandemic, with meaningful world-
wide effect: ~149,6 million cases and ~3,1
million deaths as of April 29, 2021 (2). The
recognized human-to-human transmission of
SARS-CoV-2 is through respiratory droplets
from infected individuals, mainly during close
contact (3) and to a lesser extent by touching
contaminated surfaces before contacting mu-
cous membranes (4). However, the sources
and transmission routes of the virus remain
unclear; its strong infectivity, transmissibility,
and the symptomatic features of Covid-19 su-
ggest the likelihood of other forms of spread.
SARS-CoV-2 might be transmitted through
the feco-oral route since there are proofs of
fecal contamination of SAR-CoV and MERS-
CoV and their capacities to survive in stools
(5). Currently, feco-oral transmission has not
been demonstrated. However, increasing evi-
dence suggests this mode of spread (6-14).
The aim of this paper is to highlight the most
important evidences that support the poten-
tial feco-oral transmission of SARS-CoV-2 and
the implications on COVID-19 in Venezuela.
60 Chacín-Bonilla and Chacón
Investigación Clínica 62(Suppl. 2): 2021
SARS-CoV-2 characterization
Coronaviruses belong to the Corona-
viridae family. Like other coronaviruses,
SARS-CoV-2 is a membrane-enveloped, sin-
gle-stranded, positive-sense RNA virus with
nucleocapsid, and a crown-like appearance
under an electron microscope. due to the
presence of spike glycoproteins anchored
to the envelope. SARS-CoV-2 belongs to the
genus Betacoronavirus, and its RNA ge-
nome is 29,891 nucleotides in size, encod-
ing 9,860 amino acids (15). The virus uses
the envelope-anchored spike glycoproteins
to mediate angiotensin-converting enzyme 2
(ACE2) receptor binding and entry into host
cells. It’s these receptors that act as docking
sites for the spike proteins of SARS-CoV-2 to
bind to, allowing the viral and cellular mem-
branes to fuse. Then, the virus integrates its
RNA into the cell’s own replication machin-
ery, facilitating its propagation. SARS-CoV-2
is then able to proliferate throughout the
body, creating immune responses, and caus-
ing the person to become infected (16).
ACE2s are membrane glycoproteins,
highly expressed in organs like lungs, arter-
ies, kidneys, and heart, but in the human
body their highest expression is observed
in enterocytes, being the intestine the or-
gan most affected by SARS-CoV-2 infections.
ACE2 receptors expression patterns in these
organs dictate the virus tissue tropism and
correlated with manifestations of illness in
humans (17).
Coronaviruses are common in nature
and may infect a wide range of animals and
humans, producing respiratory, gastrointes-
tinal, and neurological diseases (18). Gener-
ally, they are responsible of a wide range of
common flu and infections of the upper re-
spiratory tract. Most human emerging infec-
tious diseases are of animal origin and result
from interspecies transmission. SARS-CoV-2
is initiated by a zoonotic transmission, likely
from bats, and spreads rapidly among hu-
mans. The pangolin was suggested as a po-
tential intermediate host for the virus (19).
Evidences suggesting potential feco-oral
transmission of SARS-CoV-2
Gastrointestinal manifestations
A significant number of persons in-
fected with SARS-CoV-2 have gastrointesti-
nal symptoms. In a group of 1,099 hospital
patients with COVID-19 in China, 3.8% had
diarrhea and 5% were affected by nausea or
vomiting (6). Similarly, 103/204 (50.5%)
hospital patients with the disease had di-
gestive manifestations as their main com-
plaint (7).
Both viable SARS-CoV-2 and viral RNA,
and extended fecal shedding of viral RNA
have been found in the feces of patients
with COVID-19. SARS-CoV-2 RNA was iden-
tified in the stools of 81.8% cases, even with
a negative throat swab result (8), and in as-
ymptomatic individuals (9). In a systematic
review with meta-analysis, 934/2149 (43%)
patients tested positive for SARS-CoV-2 in
stool samples or anal swabs, with positive
test results up to 70 days after symptoms
onset. The analyses revealed a pooled posi-
tive proportion of 51.8%. From 73 hospital-
ized patients with SARS-CoV-2 infection,
39 (53.4%) tested positive for viral RNA in
stool specimens and 17(43.6%) remained
positive after becoming negative in respi-
ratory samples. Positive fecal samples for
SARS-CoV-2 of 282/443 (64%) patients re-
mained positive for a mean of 12.5 days, up
to 33 days after respiratory samples became
negative. Viable SARS-CoV-2 was found in
6/17 (35%) patients (10). In a study from
China, the median duration of the virus in
stool was 22 days, as compared to 18 days
in respiratory airways and 16 days in serum
samples (11). Patients with COVID-19 were
tested by RT-PCR: 32% (126/398) of pha-
ryngeal swabs and 29% (44/153) of fecal
samples tested positive. Live viruses were
detected, by electron microscopy, in four
SARS-CoV-2 positive fecal specimens from
two patients without diarrhea (12). SARS-
CoV-2 RNA loads could be as high as 10
8
copies per gram of feces (13).
Potential feco-oral spread of SARS-CoV-2 and implications for Venezuela 61
Vol. 62(Suppl. 2): 58 - 68, 2021
Presence of ACE2 receptor of SARS-CoV-2
in enterocytes
ACE2 receptor of SARS-CoV-2 is pres-
ent in the gastrointestinal mucosa. Indeed
ACE2 mRNA is highly expressed. In clinical
specimens, ACE2 stained positive mostly
in gastrointestinal epithelial cells (14). Re-
cently, ACE2 expression was mainly observed
in enterocytes and other types of cells. How-
ever, in the respiratory system, the expres-
sion was limited, with none or only low levels
of ACE2 protein. The virus can productively
infect human gut enterocytes, highlighting
the need to further study virus shedding in
the gastrointestinal tract, and the possibility
of feco-oral transmission (20).
Presence of SARS-CoV-2 in sewage
and surface water
SARS-CoV-2 has also been detected in
wastewaters and concern regarding the po-
tential for transmission through water have
been raised. Molecular detection of the virus
has been reported in untreated wastewaters
in USA (21), France (22), Spain (23), Italy,
England, The Netherlands, Slovenia, Czech
Republic, Canada, the United Arab Emir-
ates, India, Australia, Chile (24), Brazil (25),
and Ecuador (26). The virus was also found
in treated wastewater in France (22), Spain
(27) Italy (28), Germany (29), China (30)
and Japan (31).
So far, there are only three available in-
vestigations addressing the presence of SARS-
CoV-2 in surface waters. In Japan, the virus
was not detected in river water samples (32).
In Italy, viral RNA was found in three rivers
(33). In Ecuador, high SARS-CoV-2 RNA loads
were detected, during the peak case of CO-
VID-19, in rivers from urban streams where
sewage is discharged directly (26).
Inactivation and infectivity of SARS-CoV-2
from sewage and natural water
The inactivation of coronavirus in wa-
ter strongly depends on the temperature,
the levels of organic matter and the pres-
ence of competitors germs. Coronavirus
surrogates can survive longer in presence of
organic matter. However, the subsistence is
greatly decreased with temperatures > 20
o
C. At low temperatures, the virus presents
a higher perseverance (34). No studies on
the inactivation or removal of SARS-CoV-2 in
water are available, probably because of the
reported very low survival of the virus in sur-
face water, wastewater, sludge and biosolids
at temperatures higher than 20° C, and the
higher inactivation rate of coronavirus when
compared with others such as enteric viruses
(35). However, the virus poses high risks due
to its highly infectious nature and resistance
to conventional water and wastewater treat-
ment technologies (36).
The survival of SARS-CoV-2 in surface
water and wastewater in the warm seasons
and in tropical areas might be highly re-
duced. One study conducted in five nations
suggests a relationship between tempera-
ture and the distribution of SARS-CoV-2
(37). However, when comparing the global
climate and COVID-19 distribution charts, it
was concluded that there was no significant
association between temperature, humidity,
and the virus distribution (38).
The occurrence of SARS-CoV-2 RNA in
raw wastewaters has been demonstrated in
several countries affected by the pandemic.
Nevertheless, the presence and infectivity of
the virus in treated wastewaters and surface
waters are still very rare. There appear to be
only two studies assessing the infectivity of
SARS-CoV-2 from sewage and natural water.
In one study, raw and treated samples from
three wastewater treatment plants (WWTP)
and three river samples from Milano, Italy,
were tested for SARS-CoV-2 RNA by means
of real time RT-PCR and infectivity test on
culture cells. Viral RNA was detected in
raw, but not in treated wastewaters and riv-
ers. The results were negative for infectivity
(33). The presence of the virus in raw and
treated sewage and the infectivity in raw
sewage from nine WWTP were studied in sev-
eral cities of Germany. SARS-CoV-2 RNA was
detected in the inflow of all WWTP but infec-
62 Chacín-Bonilla and Chacón
Investigación Clínica 62(Suppl. 2): 2021
tivity was not found in any (29). The authors
suggested that sewage does not appear to be
an important route of spread. However, they
highlight the importance of carrying out fur-
ther studies given the preliminary nature of
the data (29,33).
SARS-CoV-2 presence and infectivity in
treated wastewaters and surface waters are
still poorly studied. The ability of these en-
veloped viruses to infect is associated with
the preservation of their capsid (39). It has
to be determined if the integrity and infec-
tivity of the virus is lost during the process
of the infectivity analyses. To ensure the
absence of infectivity in sewage and other
aqueous matrices, complementary analyses
have been suggested to show whether virus-
es are intact or there are only RNA strands in
the tested samples (24). Nonetheless, stud-
ies have proposed that the SARS-CoV-2 RNA
might be infectious and that the transmis-
sion of these RNAs could be a possible trans-
mission pathway of the COVID- 19 (40).
The lack of information on the ability
of SARS-CoV-2 to remain viable in wastewa-
ters and in surface waters, and the absence
of data about infectivity of detected viruses
from environmental samples, are significant
gaps in knowledge. Currently, it is not clear
whether the potential presence in wastewa-
ter effluent and pathways into freshwater el-
evates the risk of infection and the spread
of COVID-19 (41). Contact with sewage or
contaminated water cannot be ruled out. It
is interesting to note that high SARS-CoV-2
RNA loads were detected during the peak
cases of COVID-19 in Ecuador (26) and vi-
rus load rose, coinciding with the onset of
pandemic cases in Brazil (25). On the other
hand, other more resistant and infectious
mutations of SARS-CoV-2 may appear (24).
Although the feco-oral transmission of
the virus has not been shown, there are rea-
sons to believe in the existence of this route
of spread. This potential mode of transmis-
sion could be significant, especially in low-
income countries where access to clean
water, deficient sanitary facilities, and open
defecation are frequent. Discharge of raw
sewage directly into water bodies is a com-
mon practice in the vast majority of these
nations. Sewage systems are nonfunctional,
incompletely functional, or nonexistent
and the performance of WWTP is subopti-
mal (42). Under these circumstances, wa-
terborne diseases are of great concern for
public health. Pathogens can be dispersed
via wastewater and they form the basis for
environmental contamination and disease
transmission. These factors explain why the
burden from feco-oral pathogens is so high
in these areas. Although water treatment
appears to inactivate CoVs (17), a large
quantity of the world’s wastewater is re-
leased into surface waters and a prolonged
exposure to contaminated environmental
sources may potentially lead to an increase
transmission risk (21). Many researchers
warn about the possibility of SARS-CoV-2
infection through contact with sewage or
contaminated water or with the aerosols
generated in the pumping and treatment
systems, in toilets flushing and also in
faulty connections of floor drains with the
building’s main sewer pipe (35).
Potential impact of the Venezuelan crisis
on Covid-19 pandemic
In the last two decades, the serious po-
litical, economic, and social situation in Ven-
ezuela has caused an unprecedented increas-
ing humanitarian crisis. The ongoing trend
of hyperinflation and food shortages have
enhanced poverty and malnutrition rates;
96% of households are in poverty and 79%
in extreme indigence (43). The World Food
Program reported that 2,3 million (7.9%)
of Venezuelans were severely food insecure
(44). The malnutrition rate, according to
weight and age, in children under 5 years
of age, is 8%, much higher than that of Co-
lombia (3.4%), Peru (3.2%) or Chile (0.5%).
According to the height-age indicator, 30%
of these children suffer from malnutrition
(43). Childhood mortality has increased 63%
only in 6 years from 2012-2018 (45).
Potential feco-oral spread of SARS-CoV-2 and implications for Venezuela 63
Vol. 62(Suppl. 2): 58 - 68, 2021
In Venezuela, at least 82% of the popu-
lation has very occasional water access and
the quality is far below WHO standards, and
about 70% of the wastewater amount pro-
duced is not collected or treated (46). The
lack of a basic level of drinking water, en-
vironmental sanitation, and an appropriate
sanitary infrastructure, as well as the sus-
tained increase in poverty, foster the preva-
lence, spread, and dynamic epidemiology of
infectious agents. According to the World
Health Organization, environmental factors
can play a role in more than 80% of the main
diseases in the world. By 2012, 12,6 million
(23%) of deaths worldwide were attributable
to the environment (47). The illnesses with
the highest environmental contribution in-
clude diarrheal diseases (22%), parasitic
diseases, and those transmitted by vectors
(48). In fact, in the country where the in-
frastructure and health systems and public
services have collapsed, resurgence of con-
trolled diseases such as measles, diphtheria,
malaria, yellow fever, tuberculosis, cholera,
and multiple outbreaks have been observed
in the last two decades (49).
Vaccine-preventable childhood infec-
tions have reemerged in Venezuela. The
country contributed 68% (5,525/8,091) of
the cases of the measles cases and most of
the deaths (73/85) reported in the Ameri-
cas in 2018 (50). The outbreak of diphtheria
began in 2016 and up until 2019, 2,726 sus-
pected cases were registered of which 1,612
were confirmed with 280 deaths (51).
Venezuela has become the epicenter
of an increasing malaria outbreak. Between
2000 and 2015, a 359% increase in malaria
cases was observed. Between 2016 and 2017,
there was a rise of 71% of cases (52). For
Chagas disease, 16 outbreaks of oral trans-
mission were recorded nationwide between
2007 and 2018 (53).
Dengue frequency has increased more
than five-fold between 2010 and 2016; the
average incidence was 211 cases per 100,000
inhabitants (54). Six large outbreaks were
documented between 2007 and 2016 (55).
The epidemics of chikungunya of 2014 and
Zika virus of 2015 in Latin America, reached
Venezuela. The attack rate of chikungunya
at a national level was 7-14%. However, the
rate reached 40–50% in populated urban ar-
eas. During the outbreak peak, 6,975 cases
per 100,000 inhabitants were registered
(56). The incidence of Zika virus during its
epidemic peak was 2,057 cases per 100,000
persons and a total of 67,294 cases occurred
between 2015 and early 2019 (57). The re-
emergence of vector-borne diseases in the
country have represented a great public
health problem.
Feco-orally transmitted protists are en-
demic in Venezuela, and intestinal parasites
constitute a serious public health problem
that has been perpetuated over time (58,
59). For decades, we have observed rates of
parasitic infections with one or more species
of 54-92%, and rates of Ascaris lumbricoides
and Trichuris trichiura of 19.8-74.6% and
26.6-82.8%, respectively, in poor communi-
ties (60-63). Prevalence rates of over 65% in
rural communities have been reported (64).
Permanency of the high burden from feco-
oral pathogens in these areas is explained
by the relationship between social marginal-
ity and these agents, especially by the lack
of maintenance of the sewer network or its
absence in some areas (58,59). Emerging
pathogens like Cryptosporidium and Cy-
clospora cayetanensis are endemic in the
country (65, 66) and an association between
these pathogens and low socioeconomic
conditions in the area has been observed
(63,67).
Intestinal parasitoses are primarily a
cause of morbidity rather than mortality,
but they decrease resistance to other no-
sological agents and are potential factors
of diarrhea, anemia, and malnutrition that
are important causes of mortality. On the
other hand, a potential threat to patients
with COVID-19 in helminths endemic areas
is the systemic immunomodulatory effects
of these parasites through protein secretion
and by alteration of the intestinal microbi-
64 Chacín-Bonilla and Chacón
Investigación Clínica 62(Suppl. 2): 2021
ome, that may influence the severity of other
infectious diseases. In long term helminth-
infected individuals, the immunomodulation
of the innate and adaptive immune response
is characterized by a deviation to a Th2 pat-
tern cytokines. Helminth infections, that
are among the most common infectious dis-
eases in the area, may suppress the essen-
tial immune response against intracellular
pathogens (68).
Studies from Venezuelan
Warao natives showed Th2 skewed cytokine
profiles that facilitated Mycobacterium tu-
berculosis infection in patients with Ascaris
lumbricoides (69). Schistosoma infection
is correlated with increase transmission of
HIV and deworming with decrease of viral
load and improve of CD4+ counts among
HIV-infected individuals were noted (70).
Lower levels of INF-γ and higher levels of
IL-10 and TGF-β in individuals co-infected
with Plasmodium, Ascaris lumbricoides and
hookworms, as compared to those infected
only by Plasmodium, were observed (71). In
long term helminth-infected individuals co-
infected with SARS-CoV-2, the Th2 pattern
cytokines could enhance viral replication of
SARS-CoV-2 and severity of COVID-19 (72).
The possible implications of the immune-
regulatory role of helminths in humans co-
infected by SARS-CoV-2 and its effect on the
viral disease outcome must be considered.
The situation of extreme poverty, mal-
nutrition, collapse of the health and other
public services, and complex epidemiologi-
cal situation indicate the great risk of the
Venezuelan population to suffer a more dev-
astating impact of COVID-19 than in other
regions since this country is the poorest in
Latin America and is ranked second in terms
of extreme poverty worldwide, only surpassed
by Nigeria (43).
In the current scenario of the country,
and the increase in the number of SARS-Co-2
infected cases, a significant spread of CO-
VID-19 could be possible in the region and
in other countries due to the great diaspora
of Venezuelan citizens. This panorama is not
consistent with the official low number of
SARS-CoV-2 infections and deaths from CO-
VID 19 in the country (194,959 cases and
2,099 deaths as of April 29, 2021) (73) and
contrasts with the much higher figures ob-
served in other South American regions with
obvious better socioeconomic conditions.
Brazil, Argentina, Colombia, Peru, and Chile
are the nations with the most cases and
deaths in this region (2). In the Venezuelan-
Colombian border there is a great deal of
population exchange. The Ministry of Health
and Social Protection from Colombia report-
ed ~
2,8 million cases and 72,725 deaths as
of April 29, 2021 (74). This suggest that the
official figures from Venezuela appear to un-
derestimate the evidence. The situation in
Venezuela is dramatic. The country urgently
needs international humanitarian aid to alle-
viate starvation, and morbidity and mortality
from Covid-19 and several other diseases.
In conclusion, feco-oral transmission
of SARS-CoV-2 has not been shown. Howev-
er, it is conceivable and COVID-19 impact
might be high in low-income countries, es-
pecially in Venezuela due to its humanitar-
ian crisis. The lack of information about the
viability and infectivity of SARS-CoV-2 in
wastewaters and surface waters and the risk
of transmission of the infection are impor-
tant gaps in knowledge that deserve further
investigation.
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