REVISIÓN DE LA LITERATURA
SINTOMATOLOGÍA PERSISTENTE POSTERIOR A INFECCIÓN
POR SARS-COV-2. REVISIÓN DE LA LITERATURA.
Introducción: una proporción de pacientes que ha sido infectada con SARS-
CoV-2 continúa teniendo síntomas a corto y largo plazo, después de su
recuperación de la fase aguda de Covid-19.
Objetivo: describir la sintomatología persistente posterior a la infección por
SARS-CoV-2.
Métodos: artículo de revisión cientíca, tomando como fuente de información
la literatura actual publicada en bases de datos como: Biomed Central
(BMC), PubMed, Google Scholar, ScienceDirect, y Lilacs. Se hace énfasis en
publicaciones con diseño observacional, revisiones sistemáticas, metaanálisis
y estudios de revisión, en relación a los síntomas persistentes después de la
infección por SARS-CoV-2. Se considera cualquier gravedad, en pacientes
adultos, que estuvieron o no hospitalizados, con o sin comorbilidades.
Resultados: se analizaron 32 artículos, con una población de pacientes
adultos que superaron la fase aguda de la infección por SARS-CoV-2. Los
síntomas persistentes postcovid-19 descritos con más frecuencia fueron:
fatiga crónica (55.2%), cefalea (52%), disnea (39.5%), trastornos del sueño
(35.5%), depresión/ansiedad (31.2%), mialgias (30.1%), dolor torácico (26.9%),
palpitaciones (21.5%), tos (20.5%), artralgias (20.2%), ageusia/anosmia (12.4%),
alteraciones de memoria y concentración (3.6%).
Conclusión: la sintomatología postcovid-19 es diversa, con prolongación
de síntomas físicos y neuropsiquiátricos, que persisten durante 12 semanas
o más, sin una explicación alternativa. Entre un 10 a 65% de pacientes que
sobrevivieron a la etapa aguda de la infección presentan este cuadro clínico.
Por lo tanto, las afectaciones del SARS-CoV-2 en la sociedad van más allá de
la fase aguda.
Revista Médica Vozandes
Volumen 33, Número 2, 2022 77
Resumen
Palabras clave: Covid-19, SARS-CoV-2, coronavirus, post, viral.
Forma de citar este artículo: Saráuz
Rivadeneira E. PERSISTENT SYMPTOMS
AFTER SARS-COV-2 INFECTION.
LITERATURE REVIEW. Rev Med Vozandes.
2022; 33 (2): 77 - 82
1 Universidad Central del Ecuador. Facultad de
Ciencias Médicas. Posgrado de Medicina Familiar y
Comunitaria. Quito – Ecuador.
ORCID ID:
Saráuz Rivadeneira Evelyn
orcid.org/0000-0002-7403-7450
Este artículo está bajo una
licencia de Creative Com-
mons de tipo Reconocimien-
to – No comercial – Sin obras
derivadas 4.0 International.
DOI: 10.48018/rmv.v33.i2.9
*Corresponding author: Saráuz Rivadeneira
Evelyn
E-mail: essarauz@uce.edu.ec
Received: 28 – Mar – 2022
Accepted: 08 – Aug – 2022
Publish: 01 – Jan – 2023
Article history
Conflict of interest: The author has full freedom
of manuscript preparation, and there were no potential
conicts of interest.
Financial disclosure: The author has no nancial
relationships relevant to this article to disclose.
Saráuz Rivadeneira Evelyn is an Ecuadorian Social Securi-
ty Institute (IESS) scholarship recipient.
CRediT – Contributor Roles Taxonomy: Con-
ceptualización: ES, Curación (o curado) de contenidos y
datos: ES, Análisis formal de los datos: ES, Investigación:
ES, Metodología: ES, Administración del proyecto: ES,
Recursos materiales: ES, Supervisión: ES, Validación: ES,
Redacción borrador original: ES, Redacción y revisión
edición: ES.
Saráuz Rivadeneira Evelyn1*
78 Revista Médica Vozandes
Volumen 33, Número 2, 2022
INTRODUCTION
On March 11, 2020, the World Health Organization (WHO)
declared the global pandemic by Covid-19, caused by a new
coronavirus, called SARS-CoV-2. From inception to October
23, 2020, more than 50 million cases have been reported
worldwide. And until October 1, 2021, in Ecuador there are
512,000 conrmed cases and 32,836 deaths (1) .
Despite the signicant proportion of people who have been
infected with Covid-19, the clinical course of the associated
respiratory pathology, including the prevalence and
persistence of symptoms, has not been fully described. There
are patients who recover enough to be discharged from the
hospital within seven to ten days, but may not yet be free of
symptoms. Others progress to a hyperinammatory state and
Adult Respiratory Distress Syndrome (ARDS), which is associated
with high mortality, attributed to respiratory or cardiac failure (2).
The long-term effects of COVID-19 have been called “long-
term COVID-19”, “long-term COVID-19” or Long -COVID,
determined as the symptoms present after the acute stage of
the disease has been overcome. pathology, after four and even
twelve weeks, this was observed in a proportion
of patients surviving the SARS-CoV-2 infection (3) .
In the context of patients recovered from Covid-19,
the persistence of symptoms, radiological
abnormalities and compromised respiratory
function are evident. It is estimated that there are
more than fty signs and symptoms that may occur,
among which are: chronic fatigue, dyspnea,
cough, chest pain, myalgia and arthralgia. Older
adults and those patients with comorbidities are
the ones who, to a greater extent, present this
problem, without neglecting the report of cases in
young and healthy people (4).
The follow-up of patients who have overcome
the Covid-19 infection and persist with symptoms
is a new healthcare need, which requires a
multidisciplinary, protocolized and equitable
approach. For this reason, it is considered
opportune to carry out a scientic consensus
SINTOMATOLOGÍA PERSISTENTE POSTERIOR A
INFECCIÓN POR SARS-COV-2 (...) Saráuz Rivadeneira E
Introduction: a proportion of patients who have been infected with SARS-
CoV2 continue having short- and long-term symptoms after recovery from the
acute phase of Covid-19. Objective: to describe persistent symptomatology
following SARSCoV-2 infection.
Methods: scientic review article, taking as a source of information the current
literature published in databases such as: Biomed Central (BMC), PubMed,
Google Scholar, ScienceDirect, and Lilacs. It emphasizes on publishing with
observational design, systematic reviews, meta-analysis and review studies,
in relation to persistent symptoms after SARS- 2 CoV-2 infection. Any severity
is considered, in adult patients, who were or were not hospitalized, with or
without comorbidities.
Results: 32 articles were analyzed, with adult patients who overcame
the acute phase of SARS-CoV-2 infection. The most frequently described
persistent postcovid-19 symptoms were: chronic fatigue (55.2%), headache
(52%), dyspnea (39.5%), sleep disorders (35.5%), depression/anxiety (31. 2%),
myalgias (30.1%), chest pain (26.9%), palpitations (21.5%), cough (20.5%),
arthralgias (20.2%), ageusia/anosmia (12.4%), memory and concentration
disorders (3.6%).
Conclusion: postcovid-19 symptomatology is diverse, with prolongation of
physical and neuropsychiatric symptoms, persisting for 12 weeks or more,
without an alternative explanation. Between 10 to 65% of patients who
survived the acute stage of infection present this clinical picture. Therefore,
the impact of SARS-CoV-2 on society goes beyond the acute phase.
Abstract
PERSISTENT SYMPTOMS AFTER SARS-COV-2
INFECTION. LITERATURE REVIEW.
Keywords: Covid-19, SARS-CoV-2, coronavirus, post, viral.
79
REVISIÓN DE LA LITERATURA
Revista Médica Vozandes
Volumen 33, Número 2, 2022
reection, establishing how adequate clinical management
should be organized and managed (5). Despite the vast
availability of data on the clinical picture of acute Covid-19,
there is little information on the persistence of signs and
symptoms in patients who have overcome the acute stage
of this infection.
Consequently, the present work aims to describe the
persistent symptoms after SARS-CoV-2 infection. This,
regardless of having required hospitalization or not, with or
without previous comorbidities. In addition, it seeks to analyze
the duration and evolution of these symptoms. In this way,
it is oriented towards the implementation of therapeutic,
rehabilitative and individual care plans that contribute
to improving the quality of life of these patients. Its clinical
relevance is that the new knowledge acquired may be the
scientic evidence that supports more appropriate care.
METHODS
A scientic review article was carried out, taking
as a source of information the current literature
published in databases such as: Biomed Central
(BMC), PubMed , Google Scholar , ScienceDirect
, and Lilacs. The search strategy was to use MeSH
terms and Boolean operators such as: “Covid-19”
OR “SARS-CoV-2” OR “coronavirus” AND “post” AND
“viral”, in Spanish or English.
were identied (BMC: 929, PubMed: 593, Google
Scholar: 200, ScienceDirect: 186 and Lilacs: 50).
Through selection criteria, 1,856 of them were
eliminated (1,313 articles that did not refer to the
subject of study according to the title, 2 duplicate
articles, 541 editorials, letters to the editor, brief
communications and conference proceedings).
Ultimately, of the remaining 102 articles, 70 were
Records identied by database search (n = 1.958)
IDENTIFICATION
ELIGIBILITY REVISION
INCLUDED
• Biomed Central (929)
• PubMed (593)
• Google Scholar (200)
• ScienceDirect (186)
• Lilacs (50)
Excluded articles
• Qualitative design (56)
• Unclear methodology (9)
• Published in mandarin language (3)
• No ethical statements (2)
Duplicate articles. (n = 2)
Articles submitted to full reading. (n =102)
Articles included in the nal manuscript. (n =32)
Articles that did not refer0020 to the subject of
study according to the title. (n = 1.313)
Editorials, letters to the editor, short communica-
tions and conference proceedings. (n = 541)
Figure 1. Flowchart for the search and selection of literature included.
Source: Made by the authors. Year 2021.
80 Revista Médica Vozandes
Volumen 33, Número 2, 2022
eliminated (56 for having a qualitative design, 9 for not clearly
describing the methodology or instruments used, 3 for being
published in Mandarin, and 2 for not having ethical statements).
At the end of the selection process, 32 articles were included in
this research, with an emphasis on scientic publications with an
observational design, clinical studies, systematic reviews, meta
-analyses, and review studies. These are related to persistent
symptoms, after SARS-CoV-2 infection, of any degree of
severity. The characteristics correspond to adult patients, who
were hospitalized or not, with or without comorbidities and in
whose structure evolution, analysis and discussions related to
their behavior, in the short and long term, as well as the impact
on quality of life, were expressed. The posts were from January
2020 to October 2021.
Letters to the editor, unpublished research, clinical study in
the acute phase of Covid-19 or with conicts of interest were
excluded. A review of the titles and the abstract was carried
out. Those publications that passed the described lters were
considered for further reading and exhaustive analysis. With the
information collected, systematized and analyzed, the present
review work was carried out, answering the following research
question: what is the persistent symptomatology after SARS-
CoV-2 infection?
RESULTS
Persistent symptomatology after SARS-CoV-2 infection
The evidence of persistent symptoms, after the acute phase of
the SARS-CoV-2 infection has been overcome, has led to the
description of the postcovid or Long covid syndrome, which
occurs in between 10% and 65% of patients who survived
the infection. disease. It is characterized by diverse clinical
manifestations for 12 weeks or more, without an alternative
explanation. This could be attributed to the hyperinammatory
state , immunological deregulation, the sequelae of organ
damage, the variable extent of the injury, the immune response
with the generation of autoantibodies, the permanence of the
virus, the post-intensive care syndrome or adverse effects of the
medications administered (6,7) .
Sykes et al described three groups of patients who presented
post-Covid-19 symptoms: group A included myalgia and
fatigue; group B presented asthenia, anxiety and sleep
disorders; while in group C memory impairment, attention decit
and cognitive impairment were identied (8). On the other hand,
it was determined that the fact of experiencing more than ve
symptoms during the rst week of illness was associated with
prolonged Covid-19, characterized by diverse symptoms such
as: anosmia, ageusia, chronic fatigue, headache, severe
dyspnea, asthenia, weight loss, chest pain, palpitations, skin
signs, arthralgia, myalgia, digestive disorders and fever (9).
General symptoms and signs
Among the most frequent symptoms in the post-Covid-19
stage are chronic fatigue, headache, dyspnea and cough. In
addition, alterations in chest X-ray images, elevation in D- dimer
and concentration of C-reactive protein (CRP) (10). In reports
made to evaluate long-term manifestations, after
SARS-CoV-2 virus infection, it is indicated that
patients also perceived palpitations, myalgia,
depression and, less frequently, anosmia and/
or ageusia , around thirty and forty days post-
infection (11,12).
In follow-up studies, the most prevalent clinical
manifestations have been determined to be
chronic fatigue, headache and dyspnea, with
a partial recovery in around three months, after
the acute stage of the infection. Furthermore,
it is considered that when fatigue persists for six
months or more, it is chronic fatigue syndrome or
postviral fatigue (13). This is attributed to the fact
that the SARS-CoV-2 virus functions as a major
stressor, targeting the paraventricular nucleus
- hypothalamic axis, in genetically susceptible
people. Thus, dysfunction at this level acts as
the epicenter of neuroinammation , which is
driven through localized activation induced by
microglia (14).
Neurological and psychiatric symptoms
The presence of SARS-CoV-2 in the cerebrospinal
uid (CSF) shows its neuroinvasive capacity,
which induces a possible alteration of the
microstructural and functional brain integrity
in patients recovered from the acute phase of
the infection (15–17). Consequently, post-Covid-19
neurological symptoms are heterogeneous and
manifestations such as: headache, chronic
fatigue, attention decit, difculty concentrating
(brain fog), insomnia, anxiety and depression
are described (17).
In addition, focal or multifocal peripheral nerve
injury, acquired in those patients who received
prone ventilation for ARDS, can cause myopathies,
peripheral neuropathy, and delirium (18). As
additional data, the reports on Guillain -Barré
(GBS) and axonal or demyelinating variants
associated with Covid-19, in general, are
presented as a post- infectious pattern , with a
period of ve to ten days after the infection is
overcome (19 ).
Together, the hypothesis about neurodegeneration
has been raised, since coronaviruses have
been found in people with pathologies such
as: multiple sclerosis and acute disseminated
encephalomyelitis, as well as in Alzheimer’s and
Parkinson’s diseases. Previous studies raise the
probability that SARS-CoV-2 chronically affects
the Central Nervous System and that this triggers
or accelerates neurodegenerative disorders (20,21).
Cardio -respiratory symptoms
Due to cardiac symptoms in the acute phase
of the infection, postcovid-19 cardiovascular
SINTOMATOLOGÍA PERSISTENTE POSTERIOR A
INFECCIÓN POR SARS-COV-2 (...) Saráuz Rivadeneira E
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REVISIÓN DE LA LITERATURA
Revista Médica Vozandes
Volumen 33, Número 2, 2022
manifestations may occur. Among them are dyspnea, in
45%, especially in patients who required an Intensive Care
Unit (ICU); pulmonary embolism, heart failure, orthostatism,
fatal arrhythmias, and sudden cardiac death. A possible
interstitial lung injury was also evidenced, with total or partial
return to normal lung function within six to twelve months,
and the diffusing capacity for carbon monoxide (DLCO)
remained abnormal for more than a year, after recovery (22).
Other symptoms
Other symptoms that occur less frequently are: odynophagia,
nausea, vomiting, anorexia, generalized tremor and
inammatory arthralgia. The latter must be differentiated
from other similar conditions such as rheumatoid arthritis
and systemic lupus erythematosus (SLE). Severe SARS-CoV-2
infection can cause autoreactivity against a variety of
autoantigens (5,7,13,17,23).
Table 1 shows a summary of persistent post-Covid-19
symptoms.
Literature review
The purpose of this scientic review was to describe persistent
post-Covid-19 symptoms, emphasizing that sequelae can
be multiple and of variable severity. The analyzed literature
agrees that the clinical manifestations are diverse, however,
chronic fatigue predominates in most of the ndings,
followed by headache and dyspnea (4,5,8–14).
Afrin and collaborators propose that the postcovid-19 or
Long - covid syndrome is due to the hyperinammatory
state, caused by a storm of cytokines that give an
atypical response to SARS-CoV-2 infection, with which
activation acquires an important role. of mast cells (24). This
is consistent with Huang ‘s theory , for whom this syndrome
is attributed to immune, autonomic and metabolic
deregulation in postviral chronic fatigue , which would
also explain other symptoms described (25). Thus, the results
of Verstrepen et al. determine that if fatigue persists for six
months or more, it is called chronic fatigue syndrome or
postviral fatigue (26).
Regarding anosmia, it is believed that it may be related to
a lesion of the pseudostratied olfactory epithelium. This is
supported by the reports by Butowt et al., who suggest that
damage to support cells in the olfactory epithelium could
be an acceptable mechanism to explain this symptom (27).
On the other hand, Wostyn relates the damage of the
olfactory sensory neurons with a reduction in the outow
of cerebrospinal uid (CSF), through the cribriform plate
and the congestion of the glymphatic system, with the
consequent toxic accumulation within the Nervous System.
Central (CNS) (28).
According to the ndings of Paterson and collaborators,
postcovid-19 neurological symptoms appear due to the
cytokine storm and chronic viral invasion of the CNS. The
role of factors such as hydroelectrolytic alterations, acid-
base, hypo or hyperglycemia can be added, which favor
the appearance of a wide spectrum of neurological
symptoms such as: headache, anxiety, attention
decit depression, brain fog, insomnia and
neurodegenerative disorders (29).
In relation to cardio -respiratory symptoms, dyspnea
was the most frequent clinical manifestation. This is
consistent with reports by Halpin and collaborators,
which indicate that 45% of patients recovered from
Covid-19 have dyspnea, essentially those who were
in the Intensive Care Unit (ICU), in which evidence
of pulmonary brosis was found in the chest x-ray (30).
Several of these manifestations have been explained
by Dani et al as an expression of the dysfunction
of the autonomic system. The Covid-19 cytokine
response storm results from sympathetic activation
that induces the release of proinammatory
cytokines. On the contrary, vagal stimulation results in
anti-inammatory responses, which explains different
symptoms such as: orthostatism, tachycardia, or
respiratory distress (31).
Regarding pulmonary manifestations, Ahmed and
colleagues agree with studies that analyze long-term
health problems in survivors of infections by other
types of coronavirus. Reduced lung function and
abnormal diffusing capacity for carbon monoxide
(DLCO) were reported in these up to six to twelve
months after hospital discharge (32).
The main limitation of this research was that the
literature analyzed describes a great heterogeneity
of symptoms, as well as in the criteria to dene them
and in the designs used in each study. However, it is
considered that it has been possible to include the
most relevant and current knowledge in relation to
the current problems on this topic.
CONCLUSIONS
Postcovid-19 symptomatology is diverse, with
prolonged physical and neuropsychiatric symptoms,
which can persist for 12 weeks or more, without an
alternative explanation. Between 10% and 65%
of patients who survived the acute stage of the
infection present this clinical picture. Therefore, the
effects of SARS-CoV-2 on society go beyond the
acute phase.
Covid -19 symptomatology is chronic fatigue, followed
by headache and dyspnea, which persist in the short
or long term, regardless of whether or not there was
hospitalization during the acute phase of the infection.
Therefore, the heterogeneity of the clinic leads to the
need to continue the study of this health problem,
with a view to unifying the criteria to establish and
implement management and rehabilitation protocols
that are continuously updated, according to the
need for this group of patients.
82 Revista Médica Vozandes
Volumen 33, Número 2, 2022
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INFECCIÓN POR SARS-COV-2 (...) Saráuz Rivadeneira E