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International Journal of

Environmental Research
and Public Health

Article
Post-COVID Symptoms in Occupational Cohorts: Effects on
Health and Work Ability
Nicola Magnavita 1,2,3 , Gabriele Arnesano 1 , Reparata Rosa Di Prinzio 1,4 , Martina Gasbarri 1,3 ,
Igor Meraglia 1, *, Marco Merella 1 and Maria Eugenia Vacca 1

1 Post-Graduate School of Occupational Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
nicolamagnavita@gmail.com (N.M.); gabrielearnesano93@gmail.com (G.A.)
2 Department of Woman, Child and Public Health, Fondazione Policlinico Universitario Agostino Gemelli
IRCCS, 00168 Rome, Italy
3 Occupational Health Service, Local Health Unit Roma 4, 00053 Civitavecchia, Italy
4 Health Systems and Service Research, Post-Graduate School of Health Economics and Management,
Università Cattolica del Sacro Cuore, 00168 Rome, Italy
* Correspondence: igor.meraglia01@icatt.it; Tel.: +39-06-30156094

Abstract: Post-acute COVID-19 syndrome is frequently observed in workers and has a substantial
impact on work ability. We conducted a health promotion program to identify cases of post-COVID
syndrome, analyze the distribution of symptoms and their association with work ability. Of the
1422 workers who underwent routine medical examination in 2021, 1378 agreed to participate.
Among the latter, 164 had contracted SARS-CoV-2 and 115 (70% of those who were infected) had
persistent symptoms. A cluster analysis showed that most of the post-COVID syndrome cases were
characterized by sensory disturbances (anosmia and dysgeusia) and fatigue (weakness, fatigability,
tiredness). In one-fifth of these cases, additional symptoms included dyspnea, tachycardia, headache,
sleep disturbances, anxiety, and muscle aches. Workers with post-COVID were found to have poorer
quality sleep, increased fatigue, anxiety, depression, and decreased work ability compared with
workers whose symptoms had rapidly disappeared. It is important for the occupational physician
to diagnose post-COVID syndrome in the workplace since this condition may require a temporary
Citation: Magnavita, N.; Arnesano,
reduction in work tasks and supportive treatment.
G.; Di Prinzio, R.R.; Gasbarri, M.;
Meraglia, I.; Merella, M.; Vacca, M.E.
Keywords: health promotion; fatigue; anosmia; stress; sleep; anxiety; depression; treatment;
Post-COVID Symptoms in
Occupational Cohorts: Effects on
non-hospitalized; asymptomatic; long-COVID
Health and Work Ability. Int. J.
Environ. Res. Public Health 2023, 20,
5638. https://doi.org/10.3390/
ijerph20095638 1. Introduction
Academic Editor: Paul B. Tchounwou
The SARS-CoV-2 virus can affect numerous organs and systems, inducing the multi-
organ syndrome known as COVID-19 [1]. As occurs in a number of viral infections, for
Received: 30 March 2023 example EBV, HSV and HTLV [2], after the acute phase, symptoms may persist for many
Revised: 15 April 2023 weeks, or previous chronic morbid conditions may be exacerbated. This clinical picture
Accepted: 23 April 2023 is called post-acute COVID-19 syndrome [3], or long-COVID. To date, there are no fixed
Published: 25 April 2023
criteria for the diagnosis of ‘long-COVID’ [4], although this illness is known to include a
wide spectrum of clinical manifestations that may imply underlying multi-organ disorders.
A provisional definition could be symptoms and potential sequelae that continue to persist
at four weeks from onset [5]. Since these ongoing symptoms may combine, some patterns
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
have emerged: Yong and Liu observed six different clinical pictures: non-severe COVID-19
This article is an open access article
multi-organ sequelae, pulmonary fibrosis sequelae, myalgic encephalomyelitis or chronic
distributed under the terms and fatigue syndrome, postural orthostatic tachycardia syndrome, post-intensive care syndrome
conditions of the Creative Commons and medical or clinical sequelae [6].
Attribution (CC BY) license (https:// The experience of returning to work after SARS-CoV-2 infection is a highly relevant
creativecommons.org/licenses/by/ topic for occupational health. Studies performed on workers during the first phases of
4.0/). the pandemic suggest that long recovery times may be related to high severity [7], but

Int. J. Environ. Res. Public Health 2023, 20, 5638. https://doi.org/10.3390/ijerph20095638 https://www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2023, 20, 5638 2 of 13

they may also be a consequence of post-COVID [8] since long-lasting syndromes have also
been reported independently of acute phase severity, hospitalization, and treatment [3,9].
The prevalence of post-COVID cases is higher in hospitalized patients than in cases not
requiring hospitalization [10]. Studies on serious patients discharged from hospital show
that between 33% and 87% had post-COVID syndrome [1,11–16]. In non-hospitalized
cohorts, up to 67% reported long-COVID-19 [17,18].
A systematic literature search involving more than 735,000 cases up to January 2022,
revealed that 45% of COVID-19 survivors, regardless of hospitalization status, were expe-
riencing a range of unresolved symptoms at ∼4 months [19]. Prevalence was, however,
higher in hospitalized than in non-hospitalized patients (52.6% vs. 34.5%) [19]. According
to a meta-analysis conducted by the Global Burden of Disease Long COVID Collaborators
on 1.2 million individuals who had symptomatic SARS-CoV-2 infection in 2020 and 2021,
an estimated 6.2% experienced long-COVID symptom clusters [20]. The estimated mean
long-COVID symptom cluster duration was 9.0 months (95% UI: 7.0–12.0 months) among
hospitalized individuals, and 4.0 months (95% UI: 3.6–4.6 months) among non-hospitalized
individuals. Among individuals with long-COVID symptoms 3 months after symptomatic
SARS-CoV-2 infection, an estimated 15.1% (95% UI: 10.3–21.1%) continued to experience
symptoms at 12 months [20].
As of 13 March 2023, COVID-19 had infected 681 million individuals worldwide
(https://www.worldometers.info/coronavirus/ accessed on 13 March 2023). Based on
a cautious estimate of 6.2% survivors who experience persistent symptoms, this means
over 42,200,000 individuals might be affected by the long-term consequences of COVID-19.
Should this virus continue to circulate among us for years to come, the long-term effects
could increase exponentially [21].
While the long-term implications of the multi-organ manifestations of COVID-19
are now well documented, the potential occupational impact of these manifestations still
requires investigation.
The purpose of this study, conducted by the Catholic University of the Sacred Heart in
2020 and 2021 during the first four waves of COVID-19 in Italy [22], was to evaluate the
incidence of SARS-CoV-2 infection in workers and ascertain which association of symptoms
was more frequent. Moreover, the study aimed to determine whether protracted symptoms
were associated with occupational stress, sleep disturbances or mental health.

2. Materials and Methods


2.1. Population and Type of the Study
In Italy, employees who are exposed to occupational hazards have an annual medical
check-up in the workplace to assess their occupational fitness. Workers were asked to
complete a questionnaire as they awaited their medical examination. Participation in the
survey was optional. The occupational physician reviewed the questionnaire during the
subsequent physical examination and was able to delve deeper into anamnestic information
and, if necessary, send the employee to National Health Service (NHS) institutions for
diagnostic procedures or therapy.
This study was cross-sectional and retrospective. Based on the data collected, the popu-
lation was divided into three subgroups: (i) workers who had contracted the
SARS-CoV-2 infection between the start of the pandemic (in Italy, February 2020) and
the date of the medical visit (during 2021), and had passed the acute phase without continu-
ing symptoms; (ii) workers who had symptoms 4 weeks after the acute phase (post-COVID
syndrome cases); and (iii) workers who had not contracted the infection.
The study received the approval of the Lazio 1 Ethics Committee (project number 1343,
20 October 2021) and the approval of the Ethics Committee of the Catholic University of
the Sacred Heart (project number 4079, approved 4 November 2021).
The data were deposited in a publicly available database.
Int. J. Environ. Res. Public Health 2023, 20, 5638 3 of 13

2.2. Questionnaire
The workers were administered a questionnaire designed to investigate the occurrence
of SARS-CoV-2 infection, the duration and severity of symptoms and the possible presence
of post-COVID syndrome. The persistent symptoms investigated were: headache, insom-
nia, tiredness, muscle aches, weakness, anosmia, breathlessness, dysgeusia, fatigability,
malaise, tachycardia, dyspnea, anxiety, depression, brain fog, and memory loss. Workers
were also given additional questionnaires to evaluate factors potentially associated with
the syndrome.
A short Italian version [23,24] of the Effort/Reward Imbalance Questionnaire [25] was
used to measure occupational stress. According to this model, being exposed to a frequent
lack of reciprocity at work can increase the possibility of developing incident stress-related
disorders. All items have graded responses on a 4-point Likert scale, so the resulting
subscales range from 3 to 12 (effort) and from 7 to 28 (reward), respectively. The shortened
version of the questionnaire contains three questions about the effort variable and seven
about the reward variable. The weighted ratio between the two variables, effort/reward
imbalance (ERI), indicates a state of distress if values are greater than one. In this study,
the test score reliability coefficient (Cronbach’s alpha) for the ERI effort subscale was 0.777,
while Cronbach’s alpha for the reward subscale was 0.725.
The Italian version [26] of the Pittsburgh Sleep Quality Index (PSQI) [27], which
consists of 18 items, was used to evaluate the quality of sleep. Poor sleep quality is
indicated by a score of 5 or above (bad sleeper). In this research, Cronbach’s alpha
was 0.833.
Sleepiness was evaluated using the Epworth Sleepiness Scale ESS [28] consisting of
8 questions that rated, on a 4-point scale (0–3), the chances of dozing off or falling asleep
while engaged in eight different activities. An ESS score > 10 indicated excessive daytime
sleepiness (EDS). In our sample, the internal consistency measured by Cronbach’s alpha
value was 0.666.
Fatigue was measured with the Fatigue Assessment Scale [29] composed of 10 items
rated on a 5-point scale; the final score ranges from 10 to 50, with higher scores indicating
greater fatigue. A score equal to or higher than 24 has been proposed as a cut-off for
classifying fatigue on the FAS [30]. In this study, Cronbach’s alpha was 0.822.
The Italian version [31] of the Goldberg Anxiety and Depression Scale (GADS), consist-
ing of an 18-item self-report list of symptoms established specifically to assess the likelihood
of the onset of anxiety or depression, was used to measure both anxiety and depression.
Nine binary questions make up each subscale, and a point is given for each affirmative
response. An anxiety subscale score of 5 or more and a depression subscale score of 2 or
more both suggest possible clinically recognizable anxiety or depression, respectively [32].
In this study, the GADS anxiety subscale had a Cronbach’s alpha of 0.858 and the value for
the GADS depression subscale was 0.785.
Happiness was measured using the Abdel-Khalek single item (“Do you feel happy in
general?”) rated on an 11-point scale (0–10) [33].
Current work ability compared with lifetime best was measured using the first item of
the Work Ability Index (WAI) [34], rated on a 11-point scale (0–10).

2.3. Statistics
The variables were described in terms of mean and standard deviation and checked for
normality, using the Kolmogorov–Smirnov and Shapiro–Wilk tests. The issue of normality
was not critical in this study, because, as reported by Lumley et al. [35], the assumption
of normality is only required for small samples, due to the central limit theorem. With
sample sizes exceeding 30, as it is the case here, violations of the normality assumptions
are not problematic, and they become less and less problematic, even when extreme, as
the sample size increases. Comparisons between the means of the variables were made
using Student’s t-test or Mann–Whitney’s U-test, the latter for comparing ordinal variables.
Comparisons between proportions were made using Pearson’s chi-square test. We used
Int. J. Environ. Res. Public Health 2023, 20, 5638 4 of 13

k-means cluster analysis to identify groups of patients who had had similar post-COVID
symptoms so that each observation belonged to the cluster with the closest mean (cluster
centers or cluster centroid). Convergence was defined as no or small change in cluster
centers after an iterative calculation.
A linear regression model was used to evaluate the effect of individual and occupa-
tional variables on the number of post-COVID symptoms.
The IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk,
NY, USA: IBM Corp was used for the analyses.

3. Results
We examined 1378 individuals (males 462, 33.5%; mean age 48.71 ± 11.19). Most were
employed in hospitals or healthcare establishments (814, 59.1%), while the remainder came
from trade, industry, and social services (564, 40.9%). A total of 1422 individuals were
examined in 2021; the participation rate was, therefore, 96.9%.
One hundred and sixty-four of these individuals (11.9%) contracted COVID-19 in
2020–2021. The prevalence of infection was significantly higher in females (123 cases, 75%)
than in males (41, 25%) (Pearson chi square = 6.07, p = 0.014). No significant difference
in age was found between those who contracted the disease (49.74 ± 10.68 years) and
those who failed to contract it (48.57 ± 11.25) (Student’s t = 0.90, p = 0.36). 74.4% of all
registered COVID-19 cases occurred among hospital workers. This incidence of COVID-19
was significantly higher than in other workers: 122 cases occurred among hospital workers
(15%), while only 42 cases (7.2%) were reported among the remaining share of the sample
(Pearson chi square = 18.07, p < 0.001). The difference was most noticeable during the first
wave of infection when 90% of cases that occurred before June 2020 (69 out of 77) affected
hospital workers.
Most infections occurred before June 2020 (first pandemic wave, 77 cases, 47.2%).
Only a few workers reported being infected with SAS-CoV-2 in the summer between
June and September 2020 (7 cases 4.3%), while there were 79 cases of infection (48.5%)
during subsequent pandemic waves after October 2020. The course of the disease was
asymptomatic in 27 workers (16.6%), mild and without the need for treatment in 65 cases
(39.9%), and of moderate severity in 63 individuals (38.7%) who were treated at home.
Only eight workers (4.9%) had to resort to hospital treatment. In more than half of the total
number of cases, the duration of the infection was very short (less than a week (31, 19.0%))
or short (between 8 and 15 days (56, 34.4%)). In 45 cases, the acute phase lasted between 16
and 21 days (27.6%), and in 31 cases over three weeks (19.0%).
Workers who had been affected by COVID-19 reported significantly higher fatigue and
a higher risk of depression compared with controls. In the other parameters, no significant
difference was found between infected and non-infected workers (Table 1).

Table 1. Comparison between workers affected by-COVID-19 (164 cases) and controls.

COVID-19 Cases Controls Mann–Whitney U Mann–Whitney U 1


Variable
Mean ± s.d. Mean ± s.d. p p
Stress 0.87 ± 0.37 0.85 ± 0.44 0.155 0.259
Anxiety 2.58 ± 2.74 2.19 ± 2.62 0.069 0.099
Depression 1.78 ± 2.06 1.40 ± 1.99 0.005 0.330
Low sleep quality 5.50 ± 3.87 4.80 ± 3.31 0.056 0.396
Daytime sleepiness 5.14 ± 3.85 4.78 ± 3.24 0.527 0.833
Fatigue 19.10 ± 5.79 18.16 ± 5.66 0.022 0.343
Happiness 7.44 ± 1.83 7.39 ± 3.37 0.133 0.365
Work Ability 8.78 ± 1.87 8.75 ± 1.90 0.975 0.611
Note: s.d.: standard deviation, 1 = Excluding post-COVID cases.

One hundred and fifteen individuals (70% of those who became infected, 8.3% of
the sample) reported one or more symptoms persisting after the acute phase. The most
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frequent symptoms were tiredness, anosmia, dysgeusia, fatigability, muscle aches, and
headache (Table 2). Post-COVID symptoms were significantly more frequent in females
(75.6%) than in males (53.7%) (Pearson’s chi square p = 0.008). We observed no difference
in the age of those who had persistent symptoms (49.98 ± 9.93) or in those who recovered
without persistent symptoms (49.16 ± 12.34) (Student’s t, p = 0.655). The prevalence of
post-COVID complaints increased in relation to the severity of the acute form: it was
present in 37% of asymptomatic, 72% of mild cases, 81% of cases with home treatment, and
88% of hospitalized workers (chi square p < 0.0001). The duration of the acute phase also
had a relationship with the occurrence of post-COVID symptoms. They were present in
55 % of infections lasting less than one week, 64 percent of acute forms lasting up to two
weeks, 76 percent of cases lasting up to three weeks, and 90 percent of longer forms (chi
square p < 0.05). The number of symptoms manifested by each post-COVID worker was
significantly correlated with the reduction in work ability measured using the Work Ability
Index (Spearman’s correlation coefficient = −0.418 p < 0.001).

Table 2. Frequency of post-COVID symptoms.

Symptom 1 Post-COVID Cases Prevalence 2


Tiredness 77 47.0
Anosmia 63 38.4
Weakness 59 36.0
Dysgeusia 53 31.7
Fatigability 48 29.3
Muscle aches 47 28.7
Headache 45 27.4
Malaise 37 22.6
Insomnia 36 22.0
Tachycardia 33 20.1
Dyspnea 31 18.9
Anxiety 28 17.1
Breathlessness 16 9.8
Depression 15 9.1
Brain fog 12 7.3
Memory loss 11 6.7
1 Symptoms reported beyond four weeks from onset; 2 referred to all infected workers.

Moreover, 18 individuals (1.3% of the population, i.e., 11% of those who contracted the
infection) reported worsening of the morbid conditions from which they had previously
suffered. Since the health surveillance medical examinations were not motivated by the
onset of the disease or by the need to check the state of health before returning to work (a
task entrusted to the NHS in Italy), they were performed at variable intervals following
the acute phase. During medical examination in the workplace, 26 workers (2.6% of the
total, 16% of the COVID cases) reported currently suffering from symptoms linked to the
previous infection.
To verify the hypothesis that the higher levels of fatigue and depression perceived by
workers who had had COVID-19 were due to the post-COVID syndrome, we repeated the
comparisons excluding those who had reported protracted symptoms. No demonstrable
difference was observed between the survivors with post-COVID syndrome and the other
workers (Table 1, last column).
Cluster analysis enabled us to observe three different post-COVID symptom patterns.
In the iterative calculation, convergence due to no or small changes in cluster centers was
achieved after seven iterations. The most prevalent picture (47 cases) was characterized
by anosmia and dysgeusia. A numerically similar group of workers (44 cases) reported
fatigability, tiredness, and weakness. A smaller number of workers (24 cases—about one-
fifth of the total) reported a heterogeneous combination of symptoms, including headache,
Int. J. Environ. Res. Public Health 2023, 20, 5638 6 of 13

insomnia, muscle aches, dyspnea, tachycardia, malaise and anxiety, in addition to anosmia,
weakness, tiredness, and fatigability (Table 3).

Table 3. Clustering of post-COVID symptoms.

Cluster 1 Cluster 2 Cluster 3


Symptom 1
(47 Cases) (44 Cases) (24 Cases)
Anosmia 1 1
Dysgeusia 1
Weakness 1 1
Tiredness 1 1
Fatigability 1 1
Muscle aches 1
Headache 1
Insomnia 1
Dyspnea 1
Tachycardia 1
Malaise 1
Anxiety 1
Breathlessness
Depression
Brain fog
Memory loss
1 Symptoms persisting after four weeks from onset.

Workers who had symptoms more than 4 weeks after infection (post-COVID) were
found to have poorer quality sleep, increased fatigue, anxiety, depression, and decreased
work ability compared with workers whose symptoms had rapidly disappeared (Table 4).

Table 4. Comparison between workers with post-COVID syndrome and workers not reporting
persistent symptoms.

Post-COVID Cases (n = 115) Healed Workers (n = 49) Mann–Whitney U


Variable
Mean ± s.d. Mean ± s.d. p
Stress 0.86 ± 0.37 0.89 ± 0.37 0.745
Anxiety 3.00 ± 2.83 1.59 ± 2.26 0.001
Depression 2.07 ± 2.13 1.10 ± 1.74 0.002
Low sleep quality 5.93 ± 4.00 4.48 ± 3.38 0.027
Daytime sleepiness 5.26 ± 4.09 4.88 ± 3.29 0.825
Fatigue 19.95 ± 6.09 17.13 ± 4.50 0.007
Happiness 7.47 ± 1.79 7.37 ± 1.95 0.963
Work ability 8.56 ± 2.01 9.31 ± 1.36 0.012
Note: s.d.: standard deviation.

In a multiple linear regression model, the number of persistent symptoms in workers


was significantly associated with anxiety and occupational stress (Table 5). Cases of distress
among workers with post-COVID syndrome had the same prevalence as in the other
members of the group (31.1% vs. 30.1%). Thirty-five (30.4%) workers with post-COVID
were at risk of being affected by clinical anxiety, while prevalence in the rest of the sample
was 18.3% (p < 0.002). Among the workers with post-COVID syndrome, there were
54 cases of depression (47%) compared with an average prevalence of 31.5% (p < 0.001).
Sleep problems in post-COVID were more prevalent than in the rest of the group (42.5% in
post-COVID, 33.8% in others), but the difference was not significant.
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Table 5. Linear regression model assessing the effect of individual and occupational variables on the
number of post-COVID symptoms.

Standardized Coefficient Beta t p


Age 0.024 0.320 0.749
Gender 0.107 1.391 0.167
ERI −0.211 −2.565 0.011
Anxiety 0.337 2.828 0.005
Depression 0.111 0.973 0.332
Sleep quality 0.072 0.641 0.523

4. Discussion
This study, which, to the best of our knowledge, is the only one performed in the
workplace with interviews and medical examinations on all active workers, made it possible
to evaluate the prevalence of post-COVID syndrome and its impact on workers’ health and
work ability.
In this heterogeneous case study conducted by the Rome Catholic University of the
Sacred Heart on workers exposed to occupational risks in different companies, almost
12% contracted the SARS-CoV-2 infection during the first pandemic waves between 2020
and 2021. The incidence of infection in healthcare workers was much higher than in other
occupational sectors, especially at the beginning of the epidemic. The high prevalence
of infection in healthcare personnel is described in the literature. Studies conducted in
2020 enabled researchers to estimate an 11% (CI: 7–15) pooled prevalence of SARS-CoV-2
infection in healthcare workers [36]. In 2022, our own longitudinal study of anesthetists in
one of two hub-COVID-19 hospitals in central Italy, continuously and exclusively exposed
to high risk of infection, found a 20% incidence after the first four pandemic phases;
three-quarters of these infections had occurred during the first wave [37]. Another early
meta-analysis estimated an overall incidence of 10.1% (95% CI: 5.3–14.9) of COVID-19
among HCW [38]. The incidence obviously increased as the pandemic continued. A
later meta-analysis estimated a positivity rate equal to 51.7% (95% CI: 34.7–68.2), with a
prevalence of hospitalization of 15.1% and mortality of 1.5% [39].
A general unpreparedness, the lack of personal protective equipment and safety
procedures, difficulty in promptly ascertaining the existence of an infection before the
development and dissemination of rapid tests, and the guidelines that compelled workers
to remain on duty if their temperature did not exceed 37.5 ◦ C may have been among the
causal factors. Recent studies have shown that in Italy, one in five people who tested
positive for SARS-CoV-2 during the first epidemic wave of COVID-19 (from 29 February
2020 to 7 July 2020) were asymptomatic [40]. In our study of healthcare workers during the
first pandemic wave in spring 2020, one in three of the HCWs who tested positive never
manifested symptoms [41]. In the aforementioned meta-analysis, 40% (95% CI: 17–65) of
the HCWs who tested positive for COVID-19 by reverse transcription-polymerase chain
reaction were asymptomatic at the time of diagnosis [36]. While public health experts are
debating the question of whether asymptomatic and late spreaders can continue virus
transmission in the community, there is little doubt that keeping untested workers on duty
after unprotected exposure was a flaw in the healthcare system.
Although cases were mostly mild in this occupational cohort, 70% of workers who
contracted SARS-CoV-2 in the early stages of the pandemic experienced symptoms that
persisted for more than four weeks after the acute phase. In four-fifths of the cases
the ongoing symptoms consisted of anosmia/dysgeusia complex or fatigue, tiredness,
and weakness. One-fifth of cases reported a heterogeneous combination of symptoms,
with a frequent reactivation of pre-existing conditions. In our observations, as in the
literature [42,43], the frequency of post-COVID symptoms was correlated with the duration
and severity of the acute phase.
The distribution of symptoms in our cohort was consistent with what has been re-
ported in the literature. In our sample we observed a high frequency of anosmia and
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dysgeusia—two symptoms that often appear together to form a recurrent post-COVID


picture. Anosmia, i.e., the loss of or change in sense of smell, is one of the most com-
mon symptoms in the acute phase of COVID-19 and the post-COVID syndrome [44].
Chemosensory deficits are often the earliest, and sometimes the only signs of the SARS-
CoV-2 virus in otherwise asymptomatic carriers [45]. SARS-CoV-2 is a neurotropic virus
that can pass from the olfactory epithelium in the nose to infect the brain [46]. Anosmia and
dysgeusia are among the most frequently reported post-COVID symptoms in children, ado-
lescents [47] and hospitalized adults [16]. In severe cases, post-COVID-19 neurological se-
quelae include persistent symptoms of anosmia, dysgeusia, headache, fatigue, myalgia, and
sleep disturbance [48].
In our cohort, fatigue, tiredness, and weakness formed a frequent triad of post-COVID
symptoms. This finding confirmed previous observations. A meta-analysis of studies
on hospitalized and non-hospitalized patients indicated that fatigue, dyspnea, and sleep
disturbance are the most common post-COVID symptoms and may be experienced up to
12 months after the acute phase [49]. According to a systematic literature review, fatigue
affects more than 50% of patients [50]. Of the numerous post-COVID symptoms, fatigue
and dyspnea are the only ones significantly associated with acute illness severity [51]. The
neuropsychological assessment of post-COVID patients showed that fatigue and cognitive
dysfunction were the most frequent symptoms associated with loss of work capacity [52].
In a few cases, in addition to fatigue and sensory disturbances, workers experienced
dyspnea, tachycardia, muscle aches, headache, insomnia, malaise, and anxiety. These
workers often reported the reactivation of previous pathologies and had the most evident
reduction in work ability. The pattern of symptoms observed in these workers was similar
to that observed in patients hospitalized with severe forms of the virus. When compared
with patients discharged from hospital, only dyspnea frequency was lower in these subjects
affected by a mild form of the virus. Studies have shown that post-COVID can affect
both individuals who have the severest forms of the disease and those who have minor
manifestations of the acute illness, although the latter have a lower frequency of this
syndrome, as also shown in our study. Post-COVID can affect numerous organs and
systems in a similar way to COVID-19 [53]. However, a significant deterioration in the
quality of life was observed only in patients who had been admitted to an ICU [54].
In our study, post-COVID workers showed a greater risk of insomnia, anxiety, and
depression than their colleagues. Interestingly, this observation enabled us to recognize
the etiopathogenetic role of SARS-CoV-2 on mental health, thereby distinguishing it from
the action of many other occupational stressors which are common during epidemics.
Numerous studies have reported a high prevalence of anxiety and depression in health-care
workers during the pandemic; a meta-analysis estimated a pooled prevalence of 30.0% for
anxiety (95% CI, 24.2–37.05); 31.1% for depression (95% CI, 25.7–36.8), and 56.5% for acute
stress (95% CI—30.6–80.5) [55]. It is not easy to interpret these data since they are taken from
cross-sectional studies, mostly without a control group, and do not contain information on
the prior condition of the workers. Moreover, these studies do not enable us to understand
how many of the problems observed can be attributed to the disease and how many to the
type of work. Through longitudinal studies we were able to observe how the mental health
status of frontline workers varied in relation to occupational stressors associated with the
different phases of the pandemic [37], while a study conducted during the first phase of the
pandemic showed that the rate of anxiety, depression and sleep disturbances is three to four
times higher in individuals who contracted the disease than in subjects not infected [41].
The same study showed that workers who had had COVID-19 have worse sleep quality
and a higher risk of anxiety and depression than others. This difference is entirely due to
the fact that many of the sufferers developed post-COVID syndrome, since no difference
in mental health levels was detected between workers who survived the disease without
sequelae and those who were not affected by it. Anxiety, depression, poor quality sleep
and fatigue were significantly greater in post-COVID workers than in others.
Int. J. Environ. Res. Public Health 2023, 20, 5638 9 of 13

Our study revealed an association between occupational stress and anxiety and the
number of symptoms in post-COVID syndrome. Since it was a cross-sectional study, we
cannot attribute a definite interpretation to this association. We can assume that stress
and anxiety produce a greater number of disturbances or push workers to report a greater
number of symptoms. However, the opposite hypothesis, i.e., that workers with more
articulated and complex symptoms become anxious and stressed, cannot be ruled out.
Longitudinal studies based on further medical examinations in the workplace will indicate
which hypothesis is correct.
The workers who were the subject of this study were mainly employed in health
services. Healthcare workers were the most exposed to the first wave of the pandemic and
were consequently the most studied, also with reference to post-COVID symptoms.
A telephone survey conducted three months after infection among 427 health care
workers from a hospital in central Italy showed that 33.8% had persistent symptoms,
consisting mainly of widespread pain, changes in taste and smell, and asthenia. In addition,
37.2% reported insomnia, daytime sleepiness, or both [56]. In this case study, the authors
observed that the women had a greater tendency to report post-COVID symptoms, as in
our experience. They also reported an association with age, which could be due to the
fact that the telephone interviews investigated pain, a symptom not pathognomonic of
post-COVID syndrome and known to be associated with age.
A survey monkey report of a sample of British healthcare workers seropositive for
SARS-CoV-2 anti–spike IgG during the first pandemic wave, to which slightly more than
one-tenth of those affected responded, indicated that fatigue, shortness of breath and
sleep disturbances were the most common symptoms of long-COVID [57]. A study of
healthcare workers at a Stockholm hospital who were seropositive for SARS-CoV-2 anti-
spike IgG conducted via a smartphone app observed that they reported more frequent
anosmia, fatigue, ageusia, and dyspnea than workers with negative serology [58]. A Swiss
longitudinal study with weekly electronic questionnaires involving 3334 workers from
23 hospitals, 17% of whom had a positive nasopharyngeal swab test, observed an increase
in long-COVID symptoms only in cases with a positive swab, but not in workers with
positive serology. In this study, persistent symptoms were more frequent in young people,
and in women. The most common symptoms of long-COVID were exhaustion/burnout,
weakness/tiredness, and impaired taste/olfaction. The marked reduction in the number of
participants over the course of the study limited the reliability of psychometric test results;
however, the authors observed that physical activity at baseline was negatively associated
with neurocognitive impairment and fatigue scores [59]. Taken together, these studies
observed that a proportion of workers who contracted the SARS-CoV-2 infection had
long-lasting symptoms, such as fatigue, taste and smell disorders and sleep disturbances.
Women were more sensitive, while age did not show a clear association with post-COVID
symptoms. Our study confirmed these observations and furthermore evaluated the impact
of the post-COVID syndrome on anxiety, depression and quality of sleep, fatigue, sleepiness
and workability. These findings should motivate targeted prevention interventions in
the workplace.

4.1. Future Perspectives


Doctors in charge of workers’ health surveillance have been reporting very severe cases
of post-COVID syndrome to management to obtain a temporary reduction in workload
or night work which may interfere with symptoms. Moreover, occupational doctors have
also referred workers experiencing post-COVID syndrome to their general practitioner
(GP) or NHS facilities for treatment. Recent studies have shown that daily supplements
based on amino acids, minerals, vitamins, and plant extracts may improve fatigue and
muscle function [60]. Other treatment options include molecular hydrogen inhalation,
hyperbaric oxygen therapy, aerobic training, strengthening exercises, diaphragmatic breath-
ing techniques, and mindfulness training [61]. Several treatments have been proposed
for the olfactory consequences of the infection; to date, however, there is very limited
Int. J. Environ. Res. Public Health 2023, 20, 5638 10 of 13

evidence available concerning the efficacy and potentially negative effects of treatment for
persistent olfactory dysfunction resulting from COVID-19 infection [62]. Other therapeutic
approaches may be useful in chronic inflammation, metabolic alterations, endothelial dys-
function, and gut dysbiosis that concur in the pathogenesis of post-COVID syndrome [63].
Rehabilitation could improve dyspnea, anxiety, and the quality of life [64].

4.2. Limitations
This study has some limitations. The first results from the use of a convenience sample
consisting of workers subjected to surveillance in 2021. Since this sample included only
some professional categories, it cannot be extrapolated to encompass all workers. However,
the high level of participation of workers makes this study a census. The fixed schedule of
medical examinations during which promotional intervention was proposed prevented
us from examining workers at the same interval after infection. However, this procedure
is envisaged in occupational medicine to eliminate the costs of health promotion and has
proved effective even in the absence of funding. Although the cross-sectional nature of
the study precludes recognition of causality, the continuation of health surveillance in the
workplace will make it possible to detect the evolution of symptoms and the relationship
between the syndrome and psychosocial variables.

5. Conclusions
This study revealed that about three-quarters of workers who were infected with
SARS-CoV-2 experienced protracted neurosensory symptoms (anosmia and dysgeusia,
fatigability, weakness, and tiredness) sometimes associated with dyspnea, tachycardia,
headache, sleep disturbances, anxiety, and depression. Post-COVID syndrome is associated
with reduced work ability. A temporary reduction in workload and the elimination of night
shifts have been widely recommended for facilitating convalescence.

Author Contributions: Conceptualization, N.M.; methodology, N.M.; formal analysis, N.M.; inves-
tigation, N.M.; data curation, R.R.D.P., I.M.; M.M., G.A., M.E.V. and M.G.; writing—original draft
preparation, N.M.; writing—review and editing, N.M., I.M., M.E.V. and G.A. All authors have read
and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki and approved by the Ethics Committee of the Catholic University of the Sacred Heart
(project number 4079, approved 4 November 2021).
Informed Consent Statement: Informed consent was obtained from all subjects involved in
the study.
Data Availability Statement: Data are freely available in Zenodo.
Acknowledgments: We thank the workers who participated in the promotion campaign and the
occupational nurses Anna Cerrina, Stefania Ciriello, Maddalena Gabriele, Cristina Hritcu, Marcella
Labella, and Antonella Sacco, who collaborated in collecting the questionnaires. We also thank E.A.
Wright who revised the English language.
Conflicts of Interest: The authors declare no conflict of interest.

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