Stress, anxiety, depression and long COVID symptoms

Abstract

Background
The development of depression and anxiety symptoms during long COVID may partly result from the biopsychosocial effects of COVID-19 that impact mental health, rather than from the infection alone.

Aim
The present study examined the association of anxiety, depression, stress, and psychological distress levels with sociodemographic factors and symptom severity during and three months after the acute phase of COVID-19.

Methods
This cross-sectional study included 119 participants with a positive SARS-CoV-2 qPCR test. Three months after the acute phase of infection, participants completed an online survey to collect clinical information and sociodemographic data, followed by completion of the Impact of Event Scale-Revised, Depression, Anxiety, and Stress scales.

Results
During and after infection, fatigue was the most frequently reported symptom. After the acute phase of COVID-19, substantial numbers of participants presented moderate to severe psychological distress (28.5%), severe to extremely severe depression (26.05%), and severe to extremely severe stress (31.09%). Female patients presented higher stress scores than males, while individuals who reported having lost a loved one presented high psychological distress, anxiety, and depression. The presence of physical symptoms after COVID-19 and other factors such as being a woman, being married, having children, or living with someone who suffers from a disease increased vulnerability to depression, stress, and anxiety.

Conclusions
There are psychological consequences for survivors of COVID-19 associated with sociodemographic factors. Clinical strategies are needed to provide mental health care for individuals with long COVID symptoms.

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Fatigue: Biomedicine, Health & Behavior
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/rftg20
Stress, anxiety, depression and long COVID
symptoms
Elizabeth Bautista-Rodriguez, Nadia Yanet Cortés-Álvarez, César Rubén
Vuelvas-Olmos, Verónica Reyes-Meza, Thelma González-López, César Flores-
delosÁngeles, Nancy Bibiana Pérez-Silva, Héctor Alberto Aguirre-Alarcón,
Jose Luis Cortez-Sanchez, Valeria Magali Rocha-Rocha, Jorge Escobedo-
Straffon, Laura Contreras-Mioni & Maria-Lourdes Reyes-Vergara
To cite this article: Elizabeth Bautista-Rodriguez, Nadia Yanet Cortés-Álvarez, César Rubén
Vuelvas-Olmos, Verónica Reyes-Meza, Thelma González-López, César Flores-delosÁngeles,
Nancy Bibiana Pérez-Silva, Héctor Alberto Aguirre-Alarcón, Jose Luis Cortez-Sanchez, Valeria
Magali Rocha-Rocha, Jorge Escobedo-Straffon, Laura Contreras-Mioni & Maria-Lourdes Reyes-
Vergara (2022): Stress, anxiety, depression and long COVID symptoms, Fatigue: Biomedicine,
Health & Behavior, DOI: 10.1080/21641846.2022.2154500
To link to this article: https://doi.org/10.1080/21641846.2022.2154500
Published online: 19 Dec 2022.
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Stress, anxiety, depression and long COVID symptoms
Elizabeth Bautista-Rodriguez
a
, Nadia Yanet Cortés-Álvarez
b
, César
Rubén Vuelvas-Olmos
c
, Verónica Reyes-Meza
d
, Thelma González-López
e
,
César Flores-delosÁngeles
f
, Nancy Bibiana Pérez-Silva
f
, Héctor Alberto Aguirre-
Alarcón
a
, Jose Luis Cortez-Sanchez
a
, Valeria Magali Rocha-Rocha
g
,
Jorge Escobedo-Straffon
f
, Laura Contreras-Mioni
h
and Maria-Lourdes Reyes-Vergara
i
a
Laboratory of Medical & Pharmaceutical Biotechnology, Faculty of Biotechnology, Universidad Popular
Autónoma del Estado de Puebla (UPAEP), Puebla, Mexico;
b
Department of Nursing and Obstetrics, Division
of Natural and Exact Sciences, Universidad de Guanajuato, Guanajuato, Mexico;
c
Faculty of Medicine,
Universidad de Colima, Colima, Mexico;
d
Centro Tlaxcala de Biología de la Conducta, Universidad Autonóma
de Tlaxcala, Tlaxcala, Mexico;
e
Center for Psychological, Educational, and Family Development,
Comprehensive Health Clinic, UPAEP, Puebla, Mexico;
f
Molecular Diagnostic Laboratory, UPAEP, Puebla,
México;
g
School of Healthcare Science, UPAEP, Puebla, Mexico;
h
Dean of Biological Sciences, UPAEP, Puebla,
Mexico;
i
Educational innovation and academic development, UPAEP, Puebla, Mexico
ABSTRACT
Background: The development of depression and anxiety
symptoms during long COVID may partly result from the
biopsychosocial effects of COVID-19 that impact mental health,
rather than from the infection alone.
Aim: The present study examined the association of anxiety,
depression, stress, and psychological distress levels with
sociodemographic factors and symptom severity during and
three months after the acute phase of COVID-19.
Methods: This cross-sectional study included 119 participants with
a positive SARS-CoV-2 qPCR test. Three months after the acute
phase of infection, participants completed an online survey to
collect clinical information and sociodemographic data, followed
by completion of the Impact of Event Scale-Revised, Depression,
Anxiety, and Stress scales.
Results: During and after infection, fatigue was the most frequently
reported symptom. After the acute phase of COVID-19, substantial
numbers of participants presented moderate to severe
psychological distress (28.5%), severe to extremely severe
depression (26.05%), and severe to extremely severe stress
(31.09%). Female patients presented higher stress scores than
males, while individuals who reported having lost a loved one
presented high psychological distress, anxiety, and depression.
The presence of physical symptoms after COVID-19 and other
factors such as being a woman, being married, having children,
or living with someone who suffers from a disease increased
vulnerability to depression, stress, and anxiety.
Conclusions: There are psychological consequences for survivors
of COVID-19 associated with sociodemographic factors. Clinical
ARTICLE HISTORY
Received 2 June 2022
Accepted 30 November 2022
KEYWORDS
COVID-19; stress; anxiety;
depression; SARS-CoV-2
© 2022 IACFS/ME
CONTACT Elizabeth Bautista-Rodriguez elizabeth.bautista@upaep.mx Laboratory of Medical & Pharmaceutical
Biotechnology, Faculty of Biotechnology, Universidad Popular Autónoma del Estado de Puebla (UPAEP), 21 sur 1103,
Barrio de Santiago, Puebla 72410, Mexico
Supplemental data for this article can be accessed online at https://doi.org/10.1080/21641846.2022.2154500.
FATIGUE: BIOMEDICINE, HEALTH & BEHAVIOR
https://doi.org/10.1080/21641846.2022.2154500

strategies are needed to provide mental health care for individuals
with long COVID symptoms.
Introduction
The infection produced by the virus designated as severe acute respiratory syndrome cor-
onavirus type 2 (SARS-CoV-2) has dramatically affected people’s health worldwide.
Although the lungs are the primary target organs of the infection, extrapulmonary com-
plications are also frequent [1,2]. The most severely affected individuals are those older
than 60 years with comorbidities such as hypertension, diabetes, and obesity, which typi-
cally lead to the onset of more severe illness with a higher likelihood of fatal outcomes.
During the acute phase of COVID-19 (the stage when symptoms develop and are gener-
ally confirmed by laboratory tests such as PCR), patients experience potentially stressful
and traumatic symptoms that induce anxiety and, in some cases, posttraumatic stress dis-
order; the latter is more frequent in people with vulnerable comorbid conditions [3].
While COVID-19 is not considered a chronic illness, its consequences can become per-
sistent and long-term. After the acute phase, a significant proportion of patients do not
fully recover and manifest psychological and physical sequelae. The term ‘long COVID’
is defined as the presence of one or more recurrent, intermittent, or persistent symptoms
for a minimum of 12 weeks after a positive COVID-19 test that cannot be explained by an
alternative diagnosis [4–8]. Reported symptoms include fatigue, breathlessness, cough,
chest pain, palpitations, headache, joint pain, myalgia and weakness, diarrhea, rash or
hair loss, impaired balance, post-exertional malaise, and cognitive dysfunction such as
difficulties with memory and concentration [9–11]. ‘Brain fog’has been frequently
reported after the acute phase of SARS-CoV-2 infection and is characterized by mental
fatigue, lack of concentration, forgetfulness, slow thinking, difficulty concentrating, and
confusion in the process of thought [12]. These neurological effects have been attributed
to the cytokine storm that occurs during the acute phase of COVID-19; however, these
symptoms could also be confused with other neuropsychiatric disorders such as
depression or attention deficit hyperactivity disorder [13,14].
A study of patient outcomes after hospitalization with COVID-19 reported that 59% of
patients who had mild COVID-19 (i.e. did not require ventilatory support) presented long
COVID symptoms [15]. The question is whether the symptoms of long COVID are due
exclusively to the infectious process itself or could be related to other factors as well.
Sykes et al. suggested that long COVID could also be attributed to biopsychosocial
effects since the occurrence of long COVID does not always depend on the severity of
the acute phase [16]. In this context, sociodemographic factors, or the presence of dis-
orders such as depression, anxiety or posttraumatic stress may be related to some of
the persistent symptoms of long COVID.
Symptoms in patients with chronic illness may overlap with somatic symptoms of
depression [17]. Similarly, after acute COVID, patients can experience psychological conse-
quences such as an increased risk of depression, anxiety, posttraumatic stress disorder, sub-
stance abuse, fatigue, anxiety, and myalgia, in addition to common residual symptoms [5,18].
A chronic illness impairs the patient’s quality of life due in part to a loss of psychological and
2E. BAUTISTA-RODRIGUEZ ET AL.

social well-being, although these effects could also be related to sociodemographic factors
[19,20]. In this context, it has been reported that women with chronic diseases suffer higher
levels of stress and anxiety than men [21,22]. Also, feelings of isolation and loneliness after
social distancing can lead to emotional disturbances, along with emotional and behavioral
disorders, as reported by Hoffart et al [23]. who found that loneliness was associated with
both depression and anxiety. Another aspect impacting mental health is the quality of
relationships. For example, it has been reported that stable relationships contribute to
mental and physical well-being [24]. Related to educational level, Khamoushi et al. [25]
found that individuals with higher education and knowledge cope better with problems.
Additionally, age [26], household size [27], having children [28], educational level, employ-
ment status [29], and even pet ownership can affect mental health [30].
Therefore, how acute and long-term symptoms of COVID associate with factors beyond
the infection itself is essential to inform appropriate health and psychoeducation proto-
cols to improve the quality of life of patients suffering from long COVID. This study aims to
examine, in light of sociodemographic variables, the associations between the psycho-
logical factors of anxiety, depression, stress, and traumatic distress, and the symptoms
of acute phase and post-acute phase SARS-COV-2 three months after infection.
Methods
Setting and sample
Participants were recruited for this cross-sectional study through an online invitation on
the website of the Consejo de Ciencia y Tecnología del Estado de Puebla (https://www.
concytep.gob.mx/) and the UPAEP Molecular Diagnostic Laboratory. Individuals were
selected based on the following eligibility criteria: (1) age between 18 and 75 years of
age from the states of Puebla and Tlaxcala, Mexico; (2) a positive SARS-CoV-2 real-time
PCR test performed during the acute phase of the disease from a laboratory approved
by the Secretary of Health; (3) no hospitalization or ventilatory assistance during the
acute phase; (4) agreement to participate in the study by filling in and signing the
online informed consent form. Once the diagnosis for SARS-CoV-2 was confirmed, an
online questionnaire (in Spanish through the Google Forms platform: Google Inc., Califor-
nia, U.S.A.) was provided to prospective participants for eligibility screening. Participants
who met inclusion criteria were provided with the questionnaire link. All participants com-
pleted questionnaires 3 months after the acute phase (none during the active infection
phase). Participants with high stress, anxiety and depression scores were eligible to
receive 10 free sessions of psychological care, and those who required it were referred
to receive psychiatric care. Participants who reported previous psychological or psychia-
tric care or had related illnesses (of any kind such as anxiety, depression etc.) prior to pan-
demic related care were excluded from the analysis.
Measurements and instruments
Sociodemographic information
All participants were required to upload a photograph of a positive SARS-CoV-2 real-time
PCR test to ensure that they met the inclusion criteria and prevent duplicate respondents.
FATIGUE: BIOMEDICINE, HEALTH & BEHAVIOR 3

Data collected included age, sex, education level, marital status, parental marital status,
household size, employment status, and pet ownership. In addition, participants were
asked if they lived with someone with a chronic illness, if they lived with or cared for a
dependent person requiring medical care, if their job involved leaving home, and if
they had lost a loved one due to COVID-19.
COVID symptomatology
Based on the available literature [1,2,31–33], thirteen symptoms reported during the
acute phase and three months after SARS-COv-2 infection were assessed. According to
the results of Sudre et al. [34], people who experienced more than five symptoms
during the first week of illness had increased risk of developing long COVID. Given this
finding, participants in the current study with less than 5 symptoms and those with
more than 5 symptoms were divided into two groups. Supplementary Table 1 shows
the list of response options regarding symptoms during and three months after the
acute phase of COVID.
Psychological distress
The Impact of Event Scale –Revised (IES-R) was used to assess subjective distress caused
by traumatic events. IES-R is a 22-item scale that measures psychological distress resulting
from an acute psychologically traumatic event. Each item is rated on a scale ranging from
0 (not at all) to 4 (completely agree) reflecting the degree of distress during the past week
related to the traumatic event (11); in this case, having been infected with COVID-19.
Higher scores reflect higher levels of distress. Total scores were classified as normal (0–
23), mild (24–32), moderate (33–36), and severe psychological distress (>37). Cronbach’s
αfor the IES-R was 0.88 in this study. This self-administered questionnaire was previously
applied to a Mexican sample to gauge the extent of psychological distress after traumatic
and stressful experiences [35].
Depression, anxiety, and stress
The Depression, Anxiety, and Stress Scale (DASS-21) is a reliable and valid tool to assess
mental health in the Mexican population [36]. This 21-item questionnaire measures nega-
tive emotional states of depression (items 3, 5, 10, 13, 16, 17, and 21), anxiety (items 2, 4, 7,
9, 15, 19, and 20), and stress (items 1, 6, 8, 11, 12, 14, and 18). The items in each subscale
are evaluated using a 4-point Likert scale, which includes the responses: not at all (score
0), slightly (score 1), highly (score 2), and extremely (score 3). Since DASS-21 is a shorter
version of DASS (42 items), the score for each subscale is multiplied by two to calculate
final scores. Higher scores on the subscales indicate greater severity or frequency of nega-
tive emotional symptoms [36]. According to severity, depression subscale scores are
classified as normal (0–9), mild (10–12), moderate (13–20), severe (21–27), and extremely
severe (28–42) depression. Anxiety subscale scores are classified as normal (0–6), mild (7–
9), moderate (10–14), severe (15–19), and extremely severe (20–42) anxiety. Finally, stress
subscale scores are classified as normal (0–10), mild (11–18), moderate (19–26), severe
(27–34), and extremely severe stress (35–42) [37]. Cronbach’sαvalues indicated strong
internal consistency for the subscales of anxiety (0.84); depression (0.80); and stress
(0.87) and for the full scale (0.89).
4E. BAUTISTA-RODRIGUEZ ET AL.

Data analysis
Descriptive analyses were conducted to assess sociodemographic variables, psychological
outcomes, and long COVID symptoms using frequencies and percentages for categorical
variables and means and standard deviations for continuous variables. A univariate
general linear model (GLM) with main effects (linear regression) was used to measure
associations of sociodemographic characteristics and somatic long COVID symptoms
with respect to total IES-R and DASS-21 subscale scores. The Bonferroni correction was
applied to post hoc tests for the GLM. Assumptions for linear regression were verified
using residual plot analyses. Pearson’s product-moment correlation coefficients (r) were
calculated to examine the linear relationship between the number of COVID-19 symp-
toms and IES-R and DASS-21 subscale scores. The hypothesis tests were two-tailed, and
the level of significance was set at 0.05. Statistical calculations were performed with
IBM SPSS v.25 Windows software (IBM Corp., Armonk, N.Y., U.S.A.).
Sociodemographic information
The 119 recruited participants (Table 1) were largely female (66.39%), between 29 and 39
years (43.7%), of single marital status (51.3%), lived in a household size with more than 3
people (48.7%), and did not have children (55.5%). Nearly half of respondents held a
bachelor’s degree (48.7%); 62.2% were employed; 43.7% had a job that did not involve
leaving home; and 83% owned pets. Three quarters (75.6%) of participants reported
living with another person with a chronic disease; 70.6% did not live with or care for a
dependent person who required medical care, and 94% had not lost a loved one due
to COVID-19.
COVID symptomatology
The symptoms reported by participants during the acute phase and three months after
SARS-COv-2 infection are summarized in Table 2. During acute COVID-19, the most
common symptoms were fatigue (84.87%), impaired smell (68.07%), and impaired taste
(65.55%). After recovery from acute COVID-19, the predominant symptoms were
fatigue (64.71%), impaired smell (38.66%), and headache (36.97%).
Psychological distress, depression, anxiety, and stress
The overall prevalence of psychological distress, depression, anxiety, and stress among
participants three months after the acute phase of COVID-19 are shown in Table 3.On
the IES-R, 25.57% of participants reported moderate or severe psychological distress
(mean score = 23.37 ± 8.43). On the DASS-21, severe or extremely severe depression,
anxiety, and stress scores were reported by 26.05% (mean score = 13.61 ± 3.01), 45.82%
(mean score = 15.39 ± 4.90), and 31.09% of participants (mean score = 20.92 ± 8.31),
respectively. In addition, supplementary Table 2 shows that the percentages of individuals
presenting anxiety, depression and stress on the DASS-21 were significantly higher in the
group reporting less than 5 symptoms during the acute phase as compared to those who
presented more than 5 symptoms.
FATIGUE: BIOMEDICINE, HEALTH & BEHAVIOR 5

Table 1. Characteristics of participants included in the sample.
Variable n%
Sex Female 79 66.39
Male 40 33.61
Age (years) 18–28 41 34.5
29–39 52 43.7
40–50 18 15.1
>50 8 6.7
Education level Elementary school 2 1.7
Middle school 4 3.4
High school 20 16.8
Technical school 7 5.9
Bachelor’s degree 58 48.7
Postgraduate degree 28 23.5
Marital status Single 61 51.3
Married 44 37.0
Common law marriage 12 10.1
Divorced 2 1.7
Parental status No children 66 55.5
With children 53 44.5
Household size 1 10 8.4
2 20 16.8
3 31 26.1
>3 58 48.7
Employment status Unemployed 8 6.7
Student 27 22.7
Housework 9 7.6
Employed 74 62.2
Retired 1 0.8
Pet ownership Yes 100 84.0
No 19 16.0
Do you live with someone who suffers from a chronic disease? Yes 90 75.6
No 29 24.4
Do you live or care for a dependent person that requires medical care? Yes 35 29.4
No 84 70.6
Does your job involve leaving home? Yes 30 25.2
Sometimes 37 31.1
No 52 43.7
Have you lost a loved one to COVID-19? Yes 25 21.0
No 94 79.0
Data are expressed as frequencies and percentages.
Table 2. Organic symptomatology during and three months after the acute phase of COVID-19.
Symptoms
During the acute phase of COVID-19 Three months after the acute phase of COVID-19
%%
Fatigue 84.87 64.71
Impaired smell 68.07 38.66
Impaired taste 65.55 29.41
Fever (≥38°C) 59.66 22.69
Loss of appetite 57.98 15.97
Diaphoresis 52.1 24.37
Diarrhea
a
49.58 15.97
Cough 49.58 23.53
Hair loss
b
40.34 31.93
Dyspnea 40.34 29.41
Headache 30.25 36.97
Menstrual cycle changes 26.05 17.65
Data are expressed as frequencies, and percentages.
a
Diarrhea was defined as loose/watery stools which occur ≥3 times within 24 h.
b
Compared to data during the acute phase of COVID-19 infection.
Bold letters indicate the three most frequent symptoms in each phase.
6E. BAUTISTA-RODRIGUEZ ET AL.

Sociodemographic characteristics and mental health
The association of psychological distress and mental health with sociodemographic vari-
ables is shown in Table 4. Higher levels of psychological distress were associated with
being married (P= 0.037) and with a household size of 1 (P= 0.045). In addition, higher
anxiety levels were associated with being female (P= 0.016), living in a three-person
household (P= 0.002), and living with someone with a chronic illness (P= 0.003).
Finally, having lost a loved one to COVID-19 was the only variable associated with signifi-
cantly higher levels of all measured mental health characteristics: distress (P< 0.001),
depression (P< 0.001), anxiety (P< 0.001), and stress (P< 0.001).
COVID-related symptomatology and mental health
The associations between persistent symptomatology after COVID-19 recovery and
psychological distress, depression, anxiety, and stress are shown in Table 5. Higher
levels of psychological distress were significantly associated with fever (P= 0.040), loss
of appetite (P= 0.001), and dyspnea (P= 0.006). Higher depression scores were
significantly associated with dyspnea. Higher levels of anxiety were associated with
fever (P= 0.036), diarrhea (P= 0.002), menstrual cycle changes (P= 0.005), loss of appetite
(P= 0.003), and dyspnea (P= 0.019). Finally, higher levels of stress were associated with
fever (P= 0.002), fatigue (P= 0.034), loss of appetite (P= 0.001), and dyspnea (P= 0.001).
The number of symptoms three months after the acute phase of COVID-19 showed moderate
positive correlations with psychological distress, depression, anxiety, and stress scores (Table 6).
Discussion
COVID-19 is a disease that has afflicted the global population for close to three years. The
disease has been associated with post-acute impacts in many apparently recovered
Table 3. Severity of psychological distress, depression, anxiety, and stress three months after the
acute phase of COVID-19.
Scale n(%)
IES-R score (psychological distress) Normal (0–23) 71 59.66
Mild (24–32) 14 11.76
Moderate (33–36) 6 5.04
Severe (>37) 28 23.53
DASS-21 score (depression) Normal (0–9) 48 40.34
Mild (10–12) 20 6.81
Moderate (13–20) 20 16.81
Severe (21–27) 17 14.29
Extremely severe (28–42) 14 11.76
DASS-21 score (anxiety) Normal (0–6) 29 24.37
Mild (7–9) 10 8.40
Moderate (10–14) 25 21.01
Severe (15–19) 16 13.45
Extremely severe (20–42) 39 32.37
DASS-21 score (stress) Normal (0–10) 23 19.33
Mild (11–18) 27 22.69
Moderate (19–26) 32 26.69
Severe (27–34) 23 19.33
Extremely severe (35–42) 14 11.76
Data are expressed as frequencies and percentages.
FATIGUE: BIOMEDICINE, HEALTH & BEHAVIOR 7

Table 4. Association between demographic characteristics, psychological distress, depression, anxiety, and stress during the acute phase of COVID-19.
Characteristics of
participants
IES-R scale DASS-21 scale
Psychological distress Depression Anxiety Stress
B non-
standardized β95% CI P
B non-
standardized β95% CI P
B non-
standardized β95% CI P
B non-
standardized β95% CI P
Gender
Female 1.325 1.965 −2.927 to
6.858
0.431 −0.023 −0.561 −2.069
to
0.947
0.466 1.235 3.355 −6.083 to
−0.626
0.016* −0.328 −1.123 −4.139 to
1.894
0.466
Male Reference Reference Reference Reference
Age (years)
18–28 3.346 9.547 −4.325 to
23.419
0.177 0.003 0.404 3.862 to
4.681
0.853 1.346 2.256 −5.482 to
9.993
0.568 0.235 0.808 −7.745 to
9.361
0.853
29–39 0.436 1.286 −10.970
to
13.541
0.837 −0.352 −1.186 −4.964
to
2.592
0.538 0.833 1.028 −5.808 to
7.864
0.778 −1.939 −2.371 −9.927 to
5.185
0.538
40–50 0.743 1.508 −11.483
to
14.499
0.820 −0.009 −0.092 −4.097
to
3.913
0.964 0.124 0.390 −6.856 to
7.636
0.916 −0.349 −0.83 −8.193 to
7.827
0.964
> 50 Reference Reference Reference Reference
Level of education
Elementary
school
1.823 2.634 18.054 to
23.322
0.803 −1.534 −3.251 −9.629
to
3.127
0.318 −5.235 −7.252 −18.794
to 4.285
0.218 −4.711 −6.502 −19.257
to 6.253
0.318
Middle school −3.325 −7.290 −21.576
to 6.995
0.317 −1.831 −2.900 −7.303
to
1.504
0.197 −2.463 −3.741 −11.708
to 4.227
0.358 −4.222 −5.799 −14.607
to 3.008
0.197
High school −2.353 −5.179 −13.574
to 3.216
0.227 −1.385 −2.321 −4.909
to
0.267
0.079 −1.395 −2.782 −7.464 to
1.901
0.244 −2.354 −4.641 −9.817 to
0.534
0.079
Technical school −1.224 −2.686 −13.849
to 8.478
0.637 −1.248 −1.537 −4.978
to
1.905
0.381 −0.094 −0.214 −6.441 to
6.013
0.946 −1.235 −3.074 −9.957 to
3.809
0.381
Bachelor’s
degree
−0.352 −2.281 −8.613 to
4.051
0.480 −1.084 −1.141 −3.093
to
0.811
0.252 −0.263 −0.352 −3.883 to
3.180
0.845 −1.209 −2.281 −6.185 to
1.623
0.252
Postgraduate Reference Reference Reference Reference
Marital status
Single 7.367 11.192 0.274 −0.385 −1.403 0.657 −5.235 −7.255 0.204 −1.224 −2.805 0.657
8E. BAUTISTA-RODRIGUEZ ET AL.

−8.859 to
31.242
−7.584
to
4.779
−18.438
to 3.929
−15.167
to 9.557
Married 9.256 21.166 1.266 to
41.067
0.037* 1.212 1.707 −4.427
to
7.482
0.585 −1.935 −2.579 −13.769
to 8.521
0.649 1.354 3.415 −8.815 to
15.684
0.585
Common law
marriage
12.325 16.070 −5.056 to
37.196
0.136 0.152 0.350 −6.162
to
6.863
0.916 −1.092 −1.719 −13.502
to
10.064
0.775 0.255 0.700 −12.325
to
13.725
0.916
Divorced Reference Reference Reference Reference
Parental status
With children 1.245 3.483 −3.219 to
10.186
0.308 0.213 0.538 −1.529
to
2.604
0.610 0.984 1.599 −2.140 to
5.338
0.402 0.842 1.075 −3.057 to
5.208
0.610
No children Reference Reference Reference Reference
Household size
1 2.675 9.163 −18.123
to
−0.215
0.045* 0.124 0.606 −2.155
to
3.366
0.667 −0.274 −0.740 −5.673 to
4.255
0.772 0.832 1.211 −4.309 to
6.732
0.667
2 0.034 0.103 −6.921 to
7.127
0.977 0.286 0.044 −2.121
to
2.210
0.968 −0.983 −1.762 −5.680 to
2.155
0.378 0.012 0.089 −4.242 to
4.419
0.968
3−1.465 −5.135 −11.148
to 0.877
0.094 −0.843 −1.073 −2.926
to
0.781
0.257 −2.426 −5.418 −8.772 to
−2.064
0.002* −0.647 −2.145 −5.852 to
1.562
0.257
>3 Reference Reference Reference Reference
Employment status
Unemployed 3.436 7.328 −21.844
to
36.501
0.622 1.326 4.596 4.397 to
13.589
0.316 1.335 2.706 −13.566
to
18.977
0.744 5.332 9.192 −8.794 to
27.178
0.316
Student 2.346 7.038 −21.265
to
35.340
0.626 3.346 5.603 −3.122
to
14.328
0.208 2.493 4.748 −11.039
to
20.534
0.556 6.346 11.206 −6.244 to
28.656
0.208
Housework 16.332 21.237 −6.465 to
48.939
0.133 2.326 4.480 −4.060
to
13.020
0.304 1.385 1.904 −13.548
to
17.355
0.809 2.235 8.960 −8.120 to
26.039
0.304
Employed 4.125 8.127 −19.043
to
35.297
0.558 1.848 3.562 −4.814
to
11.938
0.401 1.032 3.238 −11.916
to
18.393
0.675 5.352 7.123 −9.628 to
23.875
0.405
Retired Reference Reference Reference Reference
Pet owner
Yes −2.925 −6.031 0.063 −1.059 −1.708 0.087 −1.383 −1.806 0.318 −1.326 −3.417 0.087
(Continued)
FATIGUE: BIOMEDICINE, HEALTH & BEHAVIOR 9

Table 4. Continued.
Characteristics of
participants
IES-R scale DASS-21 scale
Psychological distress Depression Anxiety Stress
B non-
standardized β95% CI P
B non-
standardized β95% CI P
B non-
standardized β95% CI P
B non-
standardized β95% CI P
−12.387
to 0.325
−3.668
to
0.251
−5.371 to
1.740
−7.336 to
0.502
No Reference Reference Reference Reference
Do you live with someone who suffers from a chronic disease?
Yes −0.834 −2.570 −8.127 to
2.987
0.365 0.832 1.373 −0.340
to
3.086
0.116 2.464 4.751 1.651 to
7.850
0.003* 0.362 2.746 −0.681 to
6.172
0.116
No Reference Reference Reference Reference
Do you live or were in charge of a dependent person that requires medical care?
Yes 1.576 2.391 −3.86 to
7.969
0.401 −0.034 −0.169 −1.888
to
1.550
0.847 0.128 0.517 −2.594 to
3.628
0.745 −0.121 −0.338 −3.777 to
3.100
0.847
No Reference Reference Reference Reference
Does your job involve leaving home?
Yes 1.067 2.029 −4.332 to
8.391
0.532 −0.943 −1.498 −3.459
to
0.463
0.134 −0.853 −1.213 −4.762 to
2.335
0.503 −1.953 −2.996 −6.968 to
0.926
0.134
Sometimes −0.032 −0.094 −6.578 to
6.391
0.977 0.046 0.296 −1.703
to
2.295
0.772 −1.248 −2.910 −0.707 to
6.527
0.115 0.466 0.592 −3.406 to
4.509
0.772
No Reference Reference Reference Reference
Have you lost a loved one to COVID-19?
Yes 15.326 26.522 20.403 to
32.642
<0.001* 5.215 7.061 5.174 to
8.947
<0.001* 9.44 11.509 8.182 to
15.009
<0.001* 9.532 14.131 10.348 to
17.894
<0.001*
No Reference Reference Reference Reference
β: beta coefficient; CI: Confidence Interval; p:p-values.
10 E. BAUTISTA-RODRIGUEZ ET AL.

Table 5. Association between physical symptomatology three months after the acute phase of COVID-19 and mental health.
Symptoms
IES-R scale DASS-21 scale
Psychological distress Depression Anxiety Stress
B non-
standardized β95% CI P
B non-
standardized β95% CI P
B non-
standardized β95% CI P
B non-
standardized β95% CI P
Fever (≥38°C)
Yes 8.235 10.729 0.510 to
20.948
0.040 −1.053 −2.447 −8.338 to
3.445
0.416 −4.234 −5.150 −9.965 to
−0.335
0.036 6.231 8.292 −13.586 to
2.999
0.002
No Reference Reference Reference Reference
Diaphoresis
Yes 1.332 2.607 −7.246 to
12.459
0.604 1.256 3.454 −2.226 to
9.134
0.233 0.053 0.474 −4.168 to
5.116
0.841 1.352 2.747 −2.326 to
7.851
0.291
No Reference Reference Reference Reference
Diarrhea
Yes −0.323 −2.758 −11.730 to
6.213
0.547 0.643 1.019 4.153 to
6.191
0.699 4.234 6.761 2.534 to
10.988
0.002 1.534 3.235 −1.412 to
7.883
0.172
No Reference Reference Reference Reference
Fatigue
Yes 4.323 6.099 −0.873 to
13.072
0.086 1.437 3.275 −0.745 to
7.295
0.110 0.824 1.993 −1.292 to
5.278
0.234 1.335 3.896 0.284 to
7.508
0.034
No Reference Reference Reference Reference
Cough
Yes 0.156 0.560 −6.818 to
7.937
0.882 −0.864 −2.286 −6.539 to
1.967
0.292 0.832 1.150 −2.325 to
4.626
0.517 0.762 1.351 −2.471 to
5.172
0.489
No Reference Reference Reference Reference
Taste impairments
Yes −2.965 −4.072 −14.013 to
5.869
0.422 −1.244 −1.802 −7.533 to
3.929
0.538 0.009 0.160 −4.524 to
4.844
0.947 −1.244 −2.544 −7.693 to
2.606
0.333
No Reference Reference Reference Reference
Smell impairments
Yes 2.466 3.526 −5.970 to
13.022
0.467 0.035 .174 −5.301 to
5.648
0.950 0.245 1.188 −3.286 to
5.662
0.603 1.324 3.205 −1.714 to
8.123
0.202
No Reference Reference Reference Reference
Hair loss
Yes 0.496 1.387 −5.710 to
8.484
0.702 −1.356 −4.789 −5.880 to
2.303
0.391 0.938 2.421 −0.923 to
5.765
0.156 0.323 1.077 −2.599 to
4.754
0.566
No Reference Reference Reference Reference
(Continued)
FATIGUE: BIOMEDICINE, HEALTH & BEHAVIOR 11

Table 5. Continued.
Symptoms
IES-R scale DASS-21 scale
Psychological distress Depression Anxiety Stress
B non-
standardized β95% CI P
B non-
standardized β95% CI P
B non-
standardized β95% CI P
B non-
standardized β95% CI P
Menstrual cycle changes
Yes 2.646 4.957 −4.069 to
13.983
0.282 0.848 1.650 −3.553 to
6.854
0.534 3.128 6.057 1.805 to
10.310
0.005 1.325 3.616 −1.060 to
8.291
0.130
No Reference Reference Reference Reference
Loss of appetite
Yes 9.267 13.885 5.386 to
22.385
0.001 2.145 3.386 −1.514 to
8.286
0.176 3.435 6.003 1.995 to
10.004
0.003 6.235 9.365 4.963 to
13.768
0.001
No Reference Reference Reference Reference
Dyspnea
Yes 7.355 12.321 1.514 to
23.207
0.006 1.048 2.425 0.109 to
15.851
0.021 3.363 5.561 0.427 to
8.200
0.019 10.235 12.795 2.844 to
19.235
0.001
No Reference Reference Reference Reference
Headache
Yes 1.356 3.213 −3.260 to
9.686
0.331 1.134 2.455 −1.277 to
6.186
0.197 1.336 2.308 −0.742 to
5.358
0.138 0.533 0.828 −2.525 to
4.181
0.628
No Reference Reference Reference Reference
β: beta coefficient; CI: Confidence Interval; p:p-values.
12 E. BAUTISTA-RODRIGUEZ ET AL.

patients, generating the syndrome now known as ‘long COVID’. The goal of this study was
to evaluate the associations between anxiety, depression, stress, and psychological dis-
tress with the number of somatic symptoms and sociodemographic aspects of individuals
three months after the acute phase of COVID. As expected, our results showed that study
participants had high levels of stress, anxiety, depression, and trauma-related distress.
This is consistent with several studies which have highlighted the close relationship
between mental health and long COVID [38,39], even in individuals without previous
mental health problems [40]. It has been suggested that the risk of being newly diag-
nosed with a psychiatric disorder after COVID-19 diagnosis nearly doubles for adults [32].
This work also highlights sociodemographic factors in long COVID that increases vul-
nerability to alterations in mental health. First, being married and living in a one-
person household were both associated with higher levels of psychological distress.
Although it has been reported that married people, on average, enjoy better mental
and physical health [41,42], it is currently recognized that those benefits depend on
the quality of the relationship. Those in distressed marriages are more likely to report
depressive symptoms and poorer health than those in happy marriages [43,44],
whereas a happy marriage may buffer the effects of stress via greater access to emotional
support [45]. This finding emphasizes that poor quality close relationships create stress
and undermine health and well-being [24], although we did not assess the quality of
the marital relationships in our participants.
Second, being female, living in a three-person household and living with someone
with a chronic illness were all associated with higher levels of anxiety. These findings
are consistent with previous studies reporting that women are at much higher risk to
develop anxiety [46,47] and that gender has been documented to be one of the main
factors weighing on social inequalities and mental health [36]. This finding is significant
when reflecting gender inequalities in the context of coping with illness. With respect
to the participants who lived with a patient with a chronic disease, these results are con-
sistent with works reporting that about one-quarter of caregivers of people with demen-
tia show clinically significant anxiety [48].
Finally, it has been suggested that family members who have lost a loved one due to
the COVID-19 pandemic are especially vulnerable to developing psychiatric illness [49,50].
Notably, having lost a loved one to COVID-19 was the only variable associated with sig-
nificantly higher levels of all measured mental health characteristics: distress, depression,
anxiety, and stress. Similarly, previous studies have suggested that patients infected with
the virus who had family members who died from COVID-19 are more susceptible to sig-
nificant mental alterations than were other patients [51], due to increased fear of dying
Table 6. Correlation between the number of COVID-19 symptoms and psychological distress,
depression, anxiety, and stress scores.
Scale
Number of symptoms three months after the acute
phase of COVID-19
rP
Psychological distress (IES-R) 0.386 <0.001
Depression (DASS-21) 0.375 <0.001
Anxiety (DASS-21) 0.598 <0.001
Stress (DASS-21) 0.518 <0.001
FATIGUE: BIOMEDICINE, HEALTH & BEHAVIOR 13

themselves from the disease [52]. Together, these results suggest the importance of
implementing strategies to minimize the psychological problems within the COVID-
affected population, including support strategies specific to each demographic group.
Additionally, our data show that, three months after the acute phase of SARS-CoV-2
infection, the most frequently reported symptoms were fatigue, impaired smell, and
headache. Fatigue was the most common musculoskeletal symptom reported in post-
COVID-19 individuals in a previous study [40]. Also, this is consistent with the typical clini-
cal symptoms of long COVID, which include tiredness, dyspnea, fatigue, headache, persist-
ent loss of smell or taste, cough, low-grade fevers, palpitations, dizziness, muscle pain, and
joint pains [9].
Moreover, we found that the number of post-COVID symptoms three months after the
acute phase of COVID-19 infection correlated positively with high levels of traumatic dis-
tress, depression, anxiety, and stress. Similar results were seen in Tomasoni et al., 2021 [53]
study, where at 1–3 months following after virological clearance from COVID-19, patients
with anxiety and depression more commonly reported symptom persistence, even after
adjustment for age, gender, and disease severity. This finding may be bidirectional:
ongoing physical symptoms could lead to poorer psychiatric health, at the same time
as increased mental health burden may present as physical symptoms [38]. It is suggested
that COVID-19 survivors have an increased rate of new onset psychiatric disorders, and
prior psychiatric disorders are associated with a higher risk of COVID-19 [54].
Similarly, a large case–control study based on electronic health records of patients in
the U.S.A. found that the odds of being diagnosed with COVID-19 were higher for patients
with attention deficit hyperactivity disorder, bipolar disorder, depression, and schizo-
phrenia [55]. Possible explanations for these associations include the possibility that
SARS-CoV-2 virus may directly cause psychiatric morbidity through cerebral infection or
neuroinflammation postulated to occur in some forms of psychiatric disorder [56].
Wang et al. [55] proposed a chain model to describe the link between physical symp-
toms and mental health via the need for health information and perceived impact of pan-
demic mediators. Excessive conflicting health information regarding the physical
symptoms of COVID-19 might exaggerate the perceived impact of the pandemic, thus
predisposing individuals to a higher risk of anxiety, depression, and stress [55].
Further, in the present study, fever, loss of appetite and dyspnea were associated with
higher rates of psychological distress, while dyspnea was associated with higher
depression score. Likewise, fever, diarrhea, menstrual cycle changes, loss of appetite
and dyspnea were associated with higher anxiety levels and finally, fever and fatigue
were associated with higher stress levels. Previous studies have found that psychiatric
ill-health at post-COVID follow-up was associated with persistent physical symptoms of
COVID-19, such as breathlessness and myalgia [38]. In addition, in patients with COVID-
19, changes in menstrual cycle, poor appetite, and dyspnea were significantly associated
with higher levels of anxiety [57–60]. In addition, Bottemanne et al. [61] found an associ-
ation between depression and dyspnea after the acute phase of COVID-19.
Psychological disturbances in patients with long COVID could lead to a deterioration of
general health, given that psychological disturbances in patients with chronic diseases
has been associated with noncompliance and inadequate response to treatments,
leading to further complications [62–64]. Failure to diagnose and treat psychological dis-
orders during long COVID may be associated with persistence of symptoms, poorer
14 E. BAUTISTA-RODRIGUEZ ET AL.

compliance with treatment, deterioration of the patient’s general condition, and higher
healthcare expenditures [41,42]. The biopsychological effects of long COVID affect not
only the patients themselves, but also their families and social environment. This study
provides evidence of the urgent need to provide psychological care to patients with
long COVID to improve their quality of life.
Limitations
Limitations of this study include its observational design, indicating that the reported cor-
relations suggest relationships between mental health and long COVID, without implying
causation [65]. Second, we did not assess mental health prior to infection with COVID-19;
thus, we cannot directly compare the prevalence of psychiatric disease pre- and post-
infection with COVID-19. Third, a self-report questionnaire was used to collect data,
which could be intrinsically biased by the health of the person at the time the question-
naire was filled out; however, the questionnaire was answered three months after the
acute phase of the infection with SARS-CoV-2. Fourth, since we did not include a non-
COVID-19 group, we cannot determine whether the associations between mental
health and sociodemographic factors are due to long COVID or are a consequence of
the COVID-19 pandemic per se. Other limitations of the study include the absence of
other potentially relevant factors, such as history of general medical conditions, although
we did exclude from the analyses participants who mentioned having pre-existing psy-
chiatric or psychological diseases prior to SARS-CoV-2 infection. Despite these limitations,
the reporting of these findings provides potentially valuable information on the conse-
quences of SARS-CoV-2 infection that could inform public policy measures to serve this
vulnerable population.
Conclusion
This study highlights the presence of physical and mental health problems during the
initial post-acute covid period that can diminish quality of life among survivors. Adults
with long COVID are likely to be referred to healthcare professionals specializing in respir-
atory or rehabilitation medicine. However, addressing significant psychological altera-
tions should also be a high priority in this population. These findings can inform
healthcare systems to integrate psychosocial assessments and interventions for COVID-
19 survivors.
Acknowledgements
The authors thank Atenas Paulina Gonzalez García, Carmen Rojas Pérez, and Sergio Vera Ramírez for
their psychological care to the participants in this study and the Department of Educational Inno-
vation and Academic Development for their clerical support. This protocol was approved by the
Research Ethics Committee of the Dean of Health Sciences of the Popular Autonomous University
of the State of Puebla (permit No. CONBIOETICA21CEI00620131021). All procedures in studies invol-
ving human participants were performed in accordance with the ethical standards of the insti-
tutional and/or national research committee and with the 1964 Declaration of Helsinki and its
later amendments, or comparable ethical standards. Informed consent was obtained from all indi-
vidual participants included in this study.
FATIGUE: BIOMEDICINE, HEALTH & BEHAVIOR 15

Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
This work was partially funded by Consejo de Ciencia y Tecnología del Estado de Puebla [grant
number 127/2020].
Notes on contributors
Elizabeth Bautista-Rodriguez Pharmacobiologist Chemist, Master and PhD in Cellular and Molecular
Neurobiology.
Nadia Yanet Cortés-Álvarez Bachelor of Nursing, PhD in Medical Sciences.
César Rubén Vuelvas-Olmos Psychologist, Master and PhD in Medical Sciences.
Verónica Reyes-Meza Degree in Psychology and Master in Neuropsychological Diagnosis and Reha-
bilitation and PhD in Neuroethology.
Thelma González-López Psychologist, Administrative Coordinator of the Psychology Clinic at
UPAEP.
César Flores-delosÁngeles Engineer and teacher in Biotechnology, Head of the molecular diagnostic
laboratory.
Nancy Bibiana Pérez-Silva Biologist, Master in Assistant Biotechnology of the UPAEP Molecular
Diagnostic Laboratory.
Héctor Alberto Aguirre-Alarcón Engineer and Master in Biotechnology.
Jose Luis Cortez-Sanchez Pharmacobiological Chemist, Master’s Degree and PhD in Biological
Sciences.
Valeria Magali Rocha-Rocha Degree in applied mathematics, master’s degree in Biostatistics in
Public Health.
Jorge Escobedo-Straffon Veterinary Doctor, Master in Biotechnology.
Laura Contreras-Mioni Pharmacobiological Chemist, Master in Clinical Pharmacology and PhD. in
biotechnology.
Maria-Lourdes Reyes-Vergara Graduate in Mathematics Education, in charge of the Department of
Educational Innovation and Academic Development.
ORCID
Elizabeth Bautista-Rodriguez http://orcid.org/0000-0003-0410-0415
Nadia Yanet Cortés-Álvarez http://orcid.org/0000-0002-0596-9107
César Rubén Vuelvas-Olmos http://orcid.org/0000-0003-3212-4166
Verónica Reyes-Meza http://orcid.org/0000-0002-2745-4032
Valeria Magali Rocha-Rocha http://orcid.org/0000-0002-6844-1633
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