Post-Traumatic Stress Disorder, Anxiety, and Depression in Post-COVID-19 Patients Undergoing Psychotherapy: A Nonrandomized Clinical Trial

Abstract

Global estimates show a 17.9% prevalence of neuropsychiatric disorders in individuals recently hospitalized with COVID-19. Cognitive behavioral therapy (CBT) has been proposed as a nonpharmacological strategy to mitigate these effects. This study examined the potential effects of CBT on anxiety, depression, post-traumatic stress disorder (PTSD), and quality of life (QoL) in post-COVID-19 patients. This prospective, nonrandomized, single-center clinical trial involved 15 patients (mean age 53.4 years) who underwent weekly CBT sessions for six weeks. Between-group differences in anxiety and depression scores were non-significant (p > 0.05); however, significant intragroup improvements were observed in anxiety (p = 0.01), depression (p = 0.01), and PTSD (p = 0.01) after the intervention. Thus, CBT was associated with reduced anxiety, depression, and PTSD as well as improved quality of life in post-COVID-19 patients. Improvements in QoL were noted mainly in the domains of functional capacity, vitality, emotional aspects, and mental health. While these findings suggest that CBT may be beneficial for post-COVID-19 patients, the small sample size, absence of a control group, and short follow-up period limit the strength of our conclusions. Therefore, the results should be considered preliminary, and further randomized controlled trials with larger sample sizes are warranted.

1. Introduction

In May 2021, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) a pandemic as the number of confirmed cases worldwide reached 160 million [1]. According to the WHO (2022), of the 376,478,335 COVID-19 cases recorded by 31 January 2022, there were 5,666,064 lethal cases [2]. The pandemic caused profound behavioral and economic changes in different countries [3]. Post-COVID-19 patients experience clinical, cognitive, emotional, and behavioral symptoms. Since the official report of the first COVID-19 outbreak in December 2019, several research groups have analyzed the neuropsychological impact of the disease [4,5].

Among individuals hospitalized with COVID-19, global estimates show a 17.9% prevalence of neuropsychiatric disorders. These rates are similar to those observed in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These neuropsychiatric disorders persisted for up to 12 months [3,6,7,8].

A recent study by Duru et al. (2023) involving individuals (<18 years of age) who lived in Turkey during the COVID-19 pandemic showed 31.9%, 45.3%, and 51.3% prevalences of posttraumatic stress disorder (PTSD), anxiety, and depression, respectively [9]. Furthermore, research in Brazil has shown a 29.7% prevalence of anxiety and 68% of depression resulting from COVID-19 [10], with a higher prevalence among young women, individuals with lower educational levels, and those with pre-existing comorbidities, anxiety, and depressive disorders [11]. The discrepancy in prevalence reported between studies is partly due to their different methodologies, populations, instruments, and cutoff points.

In a cross-sectional study with 127 Brazilian post-COVID-19 patients, Hammerle et al. (2023) analyzed cognitive impairment, including anxiety and depression, associated with long-term COVID-19. Subjective complaints of cognitive deficits, including anxiety and depression, were reported by 53% of patients [12].

Some epidemiological data have shown that individuals hospitalized for extended periods due to COVID-19 are most affected by PTSD, anxiety, and depression [13,14]. Sociodemographic characteristics, history of chronic disease (mental or physical), previous psychiatric morbidity, and trauma exposure type and intensity are the main factors associated with triggering PTSD in post-COVID-19 patients [15,16].

Neuroplastic alterations, invasive medical procedures, limited ability to communicate, high drug consumption, and long hospital stays can exacerbate or consolidate symptoms associated with PTSD [17]. According to Rogers et al. (2020), 32.2% of critically ill patients who survived COVID-19 reported symptoms of PTSD, and 14.9% reported anxiety and depression [18]. In a cohort of 1276 individuals hospitalized with COVID-19, a significant increase in mood disorders was reported during the one-year follow-up period, which negatively affected functional capacity [19].

Nonpharmacological interventions are crucial for mitigating the mental health effects of the COVID-19 pandemic. CBT has emerged as a promising approach [20,21,22]. This brief, structured therapy focuses on modifying dysfunctional thoughts and behaviors. It is especially well-suited to address the sequelae of hospital trauma, uncertainty, and social isolation experienced by patients. Given that CBT has demonstrated efficacy in treating PTSD, anxiety, and depression in other contexts, this study aimed to verify its effects on these symptoms and patient quality of life (QoL) after hospitalization for COVID-19.

2. Materials and Methods

2.1. Study Design and Participants

This was a clinical, prospective, and consecutive study conducted at a single center involving hospitalized individuals affected by COVID-19. This study followed the Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) recommendations, according to the flowchart shown in Figure 1 [23]. Participants were recruited from 2 May to 2 December 2021, through digital media, folders, and posters distributed in reference hospitals for the treatment of COVID-19. All patients involved in the study had a clinical laboratory diagnosis of COVID-19 confirmed by polymerase chain reaction tests according to the WHO guidelines. The sample included both male and female individuals aged between 18 and 75 years, who were clinically stable after hospitalization for COVID-19 confirmed by clinical and laboratory diagnoses in the nonacute phase, and who had neuropsychiatric symptoms resulting from hospitalization. The absence of previous disorders was verified through a screening questionnaire and clinical interview during the initial evaluation, in which patients reported their mental health history. Patients with prior psychiatric, neurological, or mood disorders were excluded from the study. The clinical trial was closed in February 2022 due to low demand for psychological care from post-COVID-19 patients.

The recruitment process is illustrated in Figure 1. Initially, 36 patients were assessed for eligibility. Of these, nine were excluded from the study. The remaining 27 patients began the initial assessment, but four were lost before the start of psychotherapy (three due to withdrawal from participation and one due to a change of residence). Of the 23 patients who began the intervention, eight discontinued over the six-week study period (four due to discharge, three due to return to work, and one due to hospital readmission). Therefore, the final analysis included the 15 patients who completed the intervention protocol.

2.2. Ethical Aspects

The study protocol was approved by the Research Ethics Committee of Universidade Evangelia de Goiás (process number 4,296,707) and registered at ClinicalTrials.org (NCT04982042). All participants provided written informed consent after receiving an explanation of the study procedures in a private environment.

2.3. Data Collection

This study was conducted at the Pulmonary Rehabilitation Laboratory of the Evangelical University of Goiás, located in the city of Anápolis (GO), Brazil. A clinical evaluation was performed before initiating the psychotherapy sessions to collect sociodemographic data, pre-existing comorbidities, time and place of hospitalization, presence of symptoms of anxiety, depression, PTSD, and QoL assessment. All data for each outcome were collected on standardized forms and stored in a database for further analysis. The following is a brief description of the data collection instruments used.

2.3.1. Hospital Anxiety and Depression Scale (HADS)

The HADS is used to assess anxiety and depression in the scientific literature. It consists of 14 multiple-choice questions comprising two subscales for anxiety and depression, with seven items each. Each item is scored from zero (low) to three (high), totaling a score of 0–21. Anxiety and depression severity can be classified as “normal” (0–7), mild (8–10), moderate (11–15), or severe (16–21).

The total score can also be used as a clinical indicator if it is analyzed as an index of emotional disturbance or stress [24]. A recent systematic review confirmed the scale’s high internal consistency in clinical populations, with Cronbach’s alpha values for the HADS-Total and its subscales ranging from 0.73 to 0.87 [25].

2.3.2. Impact of Events Scale-6 (IES-6)

The IES-6 was used to assess PTSD. This is an abbreviated version of the IES-R, a PTSD screening tool with established cross-cultural validity and reliability for multiple types of trauma. Despite containing only six items, the scale preserves the three sub-dimensions focused on in the original scale (intrusive, avoidance/blunting, and hypervigilance). The IES-6 is recognized for its strong reliability, with studies reporting high internal consistency and a Cronbach’s alpha typically between 0.86 and 0.91 [26]. Participants answered questions based on the previous seven days. A mean score of 1.09 was used as the threshold score for significant stress.

2.3.3. Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)

QoL was assessed using the self-administered SF-36. This instrument is easy to apply and understand. It comprises 36 questions related to eight domains, of which four relate to the physical components of QoL (functional capacity, physical aspects, pain, and general health status) and four relate to the mental components (vitality, social aspects, emotional aspects, and mental health). Scores in each of these domains range from 0 to 100, with higher scores representing better QoL within the domain in question [27]. The SF-36 is a widely validated instrument, and its eight domains have shown robust internal consistency, with Cronbach’s alpha coefficients generally exceeding the recommended value of 0.70 in most validation studies.

2.4. Psychological Intervention

CBT is a nonpharmacological treatment supported by strong evidence of its effectiveness in mitigating mental health problems. This therapy is based on the cognitive model, which hypothesizes that emotions, behaviors, and physiology are influenced by individuals’ perceptions of events.

Beck argues, “It’s not the situation itself that determines what people feel and do, but how they interpret a situation” [28]. Therefore, CBT is based on a cognitive formulation: maladaptive beliefs, behavioral strategies, and maintaining factors that characterize a specific disorder [28]. The principles of CBT involve structured sessions guided by an evolving cognitive conceptualization of the patient. This requires a strong therapeutic alliance and continuous progress monitoring. CBT is adaptable and emphasizes positivity, collaboration, and active participation. It is goal-oriented, focuses on the present, is educational in nature, and uses guided discovery to teach patients skills to identify and respond to their dysfunctional cognitions, ultimately changing their thinking, mood, and behavior [28].

In this study, a specialist psychologist with certified training and clinical experience in CBT conducted weekly 50 min sessions for six weeks. The cognitive–behavioral interventions used were psychoeducation, identification of automatic thoughts and emotions, identification of central and intermediate beliefs, cognitive restructuring, problem solving, and process evaluation. These interventions aim to help patients detect and react to dysfunctional thoughts, promote better emotional states and environmentally adaptive behavior, strengthen resilience, and improve satisfaction and general well-being [28].

The primary objective of the first session was to inspire hope and identify patients’ values, aspirations, and goals. After establishing rapport and trust, additional data were collected for cognitive conceptualization. Treatment guidance was then provided, and the cognitive model was discussed with the patient, with the psychologist always seeking opportunities to generate positive emotions. The patients’ mood was also assessed, after which an action plan was developed. The session was concluded with patient feedback. From the second session onward, the treatment plan (tailored to the individual) was followed. It had the following structure: (a) mood assessment, (b) agenda definition, (c) update and review of the action plan, (d) session summary, (e) review of the action plan, and (f) feedback. Patients were encouraged to participate in self-therapy sessions, implement their action plans, and practice their skills. The ultimate goal was to teach the patients lifelong skills to reduce or prevent relapses.

All sessions were structured according to the standard CBT model, with individualized treatment plans, goals, and action plans [29]. Upon completing six weeks of therapy, the patients were reassessed, oriented, and/or released.

2.5. Statistical Analysis and Sample Size

For continuous variables, the mean and standard deviation, median, and interquartile range (IQR) were used in the descriptive analysis. Data normality was verified using the Shapiro–Wilk test. For ordinal variables that did not have a normal distribution, the Mann–Whitney U test or Wilcoxon test was used; for those with a normal distribution, Student’s t-test was used. Descriptive analyses were performed for categorical variables and are presented as absolute and relative frequencies. Comparisons were performed using the chi-square test or Fisher’s exact test. To compare the frequencies in the same population at two time points, McNemar’s test was performed. The 5% significance level was adopted for all tests. STATA^® software (version 17.0) was used for the statistical analysis. As this was an exploratory study, no formal power calculation was performed, and convenience sampling was used. Statistical analysis was conducted based on data from the 15 participants who completed the intervention, characterizing a per-protocol analysis. Due to the nature of the intervention, blinding of the participants and therapists was not feasible. However, to minimize bias, the researchers involved in statistical data analysis were blinded to the group allocation of the patients (WG or ICUG).

3. Results

The final sample included 15 patients, seven of whom were hospitalized in the ward (WG) and eight in the intensive care unit (ICUG). The mean age was 53.4 years. No significant differences were observed between the groups at baseline in terms of age, sex, self-reported race, education, comorbidities, or length of hospital stay (p > 0.05 for all;

Table 1. Clinical and sociodemographic characterization of the two groups of patients.

Variables	Total (n = 15)	WG (n = 7)	ICUG (n = 8)	p
Age, mean (sd)	53.4 (14.1)	51.7 (17.4)	54.9 (11.4)	0.68 1
Sex, n (%)				0.28 2
Female	10 (66.7)	6 (85.7)	4 (50)
Male	5 (33.3)	1 (14.3)	4 (50)
Self-reported race, n (%)				0.5 2
White	2 (13.4)	0	2 (25.0)
Brown	8 (53.3)	5 (71.4)	3 (37.5)
Black	5 (33.3)	2 (28.6)	3 (37.5)
Educational status, n (%)				1 2
Incomplete elementar school	2 (13.3)	1 (14.3)	1 (12.5)
Complete primary school	3 (20.0)	1 (14.3)	2 (25.0)
High school	7 (46.7)	3 (42.9)	4 (50.0)
University education	3 (20.0)	2 (28.6)	1 (12.5)
Comorbidities, n (%)
DM	4 (26.7)	1 (14.3)	3 (37.5)	0.56 2
SAH	6 (40.0)	2 (28.6)	4 (50.0)	0.6 2
Obesity	3 (20.0)	0	3 (37.5)	0.2 2
Anxiety, n (%)	8 (53.3)	2 (28.6)	6 (75.0)	0.13 1
Depression, n (%)	3 (20.0)	2 (28.6)	1 (12.5)	0.56 1
Hospitalization time, n (%)	11.3 (10.1)	6.4 (6.5)	15.5 (11.2)	0.08 1

Note: DM: diabetes Mellitus; WG: ward group; ICUG: intensive care unit group; SAH: systemic arterial hypertension; Values in mean and standard deviation (sd) or absolute (n) and relative (%) frequencies. ¹ Student’s t-test; ² Fisher’s exact test.

). Baseline levels of anxiety and depression were also similar between the groups (p > 0.05).

Comparisons between the WG and ICUG groups revealed no statistically significant differences before and after the intervention (

Table 2. Anxiety, depression, and post-traumatic stress disorder.

	Post-Intervention			p ICUG Pre x Post 2			p WG Pre x Post 2	p ICUG Pre x Post 2
	WG (n = 7)	ICUG (n = 8)	p	WG (n = 7)	ICUG (n = 8)	p
IES			0.2			1	1	1
<10	2 (28.6)	0		6 (85.7)	7 (87.5)
≥10	5 (71.4)	8 (100.0)		1 (14.3)	1 (12.5)
TEPT			1			---	0.38	0.34
<1.09	4 (57.1)	4 (50.0)		7 (100.0)	8 (100.0)
≥1.09	3 (42.9)	4 (50.0)		0	0
Depression (HADS-D)			0.53			0.56	---	---
Unlikely diagnosis	1 (14.3)	2 (25.0)		6 (85.7)	5 (62.5)
Possible diagnosis	4 (57.1)	2 (25.0)		1 (14.3)	3 (37.5)
Probable diagnosis	2 (28.6)	4 (50.0)
Anxiety (HADS-A)			1			0.56	---	---
Unlikely diagnosis	1 (14.3)	1 (12.5)		5 (71.4)	7 (87.5)
Possible diagnosis	4 (57.1)	4 (50.0)		2 (28.6)	1 (12.5)
Probable diagnosis	2 (28.6)	3 (37.5)

Note: WG: ward group; ICUG: intensive care unit group; HADS: hospital anxiety and depression scale; HEI: scale of event impact; PTSD: post-traumatic stress disorder. The number ² refer to the statistical test that was used.

). Anxiety and depression scores (

Table 3. Anxiety, depression, and post-traumatic stress disorder before and after psychotherapy.

Variable	Pre-Intervention		Pos-Intervention		Analysis Pre vs. Post
	WG Mean (DP)	ICUG Mean (DP)	WG Mean (DP)	ICUG Mean (DP)	WG (p; Cohen’s d)	ICUG (p; Cohen’s d)
TEPT	13.43 (4.92)	17.50 (3.78)	7.57 (3.50)	7.25 (3.49)	0.001; 1.19	0.004; 2.71
Depression (HADS)	9.29 (3.77)	10.00 (4.93)	5.57 (3.05)	4.50 (2.93)	0.014; 0.99	0.014; 1.12
Anxiety (HADS)	9.86 (3.34)	11.13 (3.80)	4.43 (2.44)	5.25 (3.37)	0.014; 1.63	0.014; 1.55

Note: WG: ward group; ICUG: intensive care unit group; HADS: hospital anxiety and depression scale; PTSD: post-traumatic stress disorder; SD: standard deviation; Cohen’s d: effect size. Values are presented as mean (standard deviation).

) and QoL (

Table 4. Quality of life before and after psychotherapy.

	Pre-Intervention			Post-Intervention			p ICUG Pre x Post 2	p WG Pre x Post 2
SF-36	ICUG	WG	p 1	ICUG	WG	p 1
Functional capacity	28.7 (19.3)	50.7 (30.6)	0.11	56.2 (25.6)	62.1 (24.5)	0.65	0.01	0.17
Physical aspects	0	42.8 (42.6)	0.006 2	28.1 (33.9)	46.4 (36.6)	0.33	0.04	0.79
Pain	55.5 (30.0)	58.6 (27.2)	0.84	71.2 (27.7)	64.6 (24.9)	0.63	0.13	0.41
General health status	48.6 (15.1)	50.3 (19.2)	0.85	55.5 (11.6)	64.6 (16.9)	0.24	0.18	0.01
Vitality	49.4 (18.0)	50.7 (7.3)	0.55	63.1 (18.7)	62.1 (20.8)	0.92	0.01	0.12
Social aspects	48.4( 25.4)	55.3 (25.9)	0.61	65.6 (23.8)	67.8 (27.8)	0.87	0.12	0.15
Emotional aspects	25 (23.8)	61.9 (35.6)	0.01	58.3 (38.8)	57.1 (16.2)	0.94	0.01	0.8
Mental Health	52.7 (22.3)	52.6 (14.7)	0.98	66.5 (21.8)	66.8 (17.5)	0.97	0.02	0.01

Note: SF-36: Short-Form Health Survey-36 itens; WG: ward group; ICUG: intensive care unit group. Values presented as mean (standard deviation).¹ Student’s t-test; ² Mann–Whitney test.

) remained similar after six weeks of CBT (p > 0.05). Similarly, categorical analysis of anxiety, depression, and PTSD symptoms showed no significant post-intervention differences between the groups (Table 2).

Intragroup Changes (Pre- vs. Post-Intervention)

Despite the absence of statistically significant between-group differences, clinically relevant and statistically significant improvements were observed within each group after the psychotherapeutic intervention (Figure 2). The magnitude of these changes, as assessed by Cohen’s d, indicates a large effect size for all variables (Table 3).

Specifically, significant symptom reductions with large effect sizes were found for the following:

• PTSD: both in the WG group (p = 0.001; d = 1.19) and ICUG group (p = 0.004; d = 2.71, 95% CI [1.19, 4.05]).
• Anxiety: both in the WG group (p = 0.014; d = 1.63) and ICUG group (p = 0.014; d = 1.55, 95% CI [0.49, 2.51]).
• Depression: both in the WG group (p = 0.014; d = 0.99) and ICUG group (p = 0.014; d = 1.12, 95% CI [0.16, 1.98]).

Within-group improvements in QoL were observed across several domains (Table 4). However, after applying a Bonferroni correction for multiple comparisons (α < 0.00625), these improvements were not statistically significant. However, the ICUG group showed positive changes in functional capacity, physical aspects, vitality, and emotional aspects, whereas the WG group showed positive changes in general and mental health.

4. Discussion

4.1. Interpretation of Results

This study aimed to investigate the effects of CBT on anxiety, depression, PTSD, and QoL in patients previously hospitalized with COVID-19. In this clinical trial, no significant differences were found between the ward and ICU groups in terms of socio-demographic and clinical variables. Both groups presented similar baseline levels of anxiety, depression, and PTSD.

No significant between-group differences were found in terms of age, sex, self-reported race, comorbidities, or length of hospitalization. WG and ICUG patients were found to be similar, with approximately half of the sample presenting with symptoms of anxiety, depression, and PTSD.

This rate exceeded the results reported in a recent meta-analysis involving 31 studies, in which the prevalence of anxiety and depression symptoms among post-COVID-19 patients was 47% and 45%, respectively [30]. A retrospective study of 402 COVID-19 survivors showed that 56% had at least one psychiatric disorder, which echoes a review that demonstrated a high prevalence of PTSD, anxiety, and depression in this population [31,32]. A six-month follow-up study also reported that 57.3% of patients without a previous psychiatric history developed mental disorders after hospitalization for COVID-19 [33].

Our findings, which indicate a high prevalence of neuropsychiatric symptoms, are consistent with the vast body of literature on this topic. Several follow-up studies have documented persistent rates of PTSD, anxiety, and depression in COVID-19 survivors, months after hospital discharge [33,34,35]. In particular, factors such as age and length of hospital stay have been found to correlate with worsening mental health. This is consistent with the challenges faced by the patients in our sample. The lack of significant differences between patients hospitalized in the ward and ICU is consistent with other studies that found no differences in PTSD or anxiety symptoms between these patient profiles [33]. The literature also describes potential risk factors, including female sex, high symptom prevalence, presence of comorbidities, age, prolonged hospitalization, administration of sedatives, functional changes, and living in low-income countries [36,37].

In addition, unique pandemic elements can affect survival outcomes, including rampant circulation of misinformation, bed shortages, ICU stays, use of mechanical ventilation, treatment-related neglect in health facilities, lack of a family presence in the hospital, limited post-acute care rehabilitation, widespread economic recession, and uncertainty about disease prognosis and adverse outcomes [38].

Sociodemographic characteristics, previous psychiatric morbidity, and the type and intensity of trauma exposure are the primary factors associated with PTSD in post-COVID-19 patients [15]. According to the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5), repeated or extreme exposure to aversive details of traumatic events, such as the COVID-19 pandemic, can be potentially aggravating with acute and chronic implications for both individuals and the community [39].

A recent systematic review reported that PTSD symptoms often persist for several months after hospitalization, albeit with varying degrees of severity [40,41]. These symptoms correlate with infection through direct and indirect mechanisms; however, the underlying etiology seems more complex and multifactorial, involving environmental, psychological, and biological factors [41].

Trauma-focused interventions, particularly psychotherapy, are more effective than pharmacological approaches in reducing PTSD symptoms [42,43], reinforcing the relevance of CBT in this context.

Regarding QoL, which refers to the level of well-being perceived by the individual in different domains of their life and its impact on general health, a review study demonstrated hospitalization as a potential agent for decline in QoL [44]. This study showed that both individuals who were hospitalized in the ward and ICU showed significant improvement in the mental health domain after the psychological intervention. These findings indicate that, regardless of disease severity, levels of anxiety and stress can be gradually reduced over time with the use of psychotherapy [13]. Several studies have documented significant impairments in QoL in patients after COVID-19 hospitalization [45,46,47]. Persistent fatigue, pain, and mental health symptoms have been reported up to one year after discharge [48,49].

In line with the evidence presented, CBT was associated with reduced anxiety and depression and improved QoL in both ward and ICU patients in this study. This suggests that psychological interventions may contribute to functional and emotional recovery. Although these changes cannot be exclusively attributed to CBT due to the noncontrolled design, improvements may be linked to cognitive restructuring strategies, coping skills, and therapeutic engagement. Similar benefits have been reported in other cohorts and rehabilitation programs. Significant reductions in anxiety, depression, and PTSD were observed after psychotherapeutic interventions, unlike in patients receiving usual care [22,50,51].

By promoting daily activity planning and adaptive behaviors, psychotherapy contributes to mood improvement and functional recovery. This is reflected in the SF-36 domains of vitality, functional capacity, and mental health [22]. Evidence from randomized trials and clinical programs further supports CBT as an effective tool to reduce psychiatric symptoms, particularly in post-COVID-19 patients and those with chronic diseases that require ICU care [22,52,53,54,55,56]. In addition to symptom relief, psychotherapy fosters resilience, emotional stability, and the reframing of life experiences, with interdisciplinary rehabilitation and social support playing complementary roles in enhancing recovery and overall QoL [57,58]. Despite these limitations, our findings reinforce the role of CBT as a relevant strategy for addressing persistent psychological sequelae in COVID-19 survivors.

4.2. Implications

The results of this exploratory study, while preliminary, show important clinical implications. The findings suggest that a brief psychotherapeutic intervention, such as CBT, may be a viable non-pharmacological alternative for reducing the effects of PTSD, anxiety, and depression in post-COVID-19 patients. Specifically, the intervention in this study incorporated CBT-based strategies such as psychoeducation, autofocus, cognitive constraint, and problem-solving. This approach is supported by Gangemi et al. (2019), who demonstrated cognitive techniques align with broader strategies—such as the Pie Technique, Cumulative Probability, and the Inverted Pyramid, which reduce the overestimation of the probability of threatening events—helping patients detect and respond to dysfunctional thoughts and promote adaptive behavior. These cognitive restructuring methods effectively decrease the perceived likelihood of negative outcomes by counteracting hyper-focalization and promoting alternative, more balanced interpretations. In clinical practice, incorporating such targeted CBT components—like exposure exercises, behavioral activation, and probability reappraisal tasks—may enhance emotional regulation and adherence to therapy in post-COVID-19 survivors [59].

The large effect sizes, particularly those related to PTSD symptoms in ICU survivors (d = 2.71), highlight the potential of this therapeutic approach to generate significant clinical improvements. In a similar line, systematic evidence on further acceptance and commitment therapy (ACT), another highly effective and adaptable transdiagnostic behavioral intervention, has also demonstrated substantial benefits in reducing symptom severity, enhancing emotional regulation, and increasing psychological flexibility across a broad spectrum of mental health conditions, including anxiety and depression. These outcomes are largely associated with ACT’s core processes—mindfulness, cognitive defusion, and value-based behavioral change—which contribute to improved psychological well-being and sustained symptom reduction. Moreover, its versatility has been evidenced through successful implementation in digital and hybrid formats, including videoconferencing and bibliotherapy. Collectively, these findings reinforce the relevance of transdiagnostic and process-based interventions in promoting emotional regulation and long-term recovery across diverse populations and treatment settings [60].

In practical terms, integrating CBT- and ACT-based interventions into rehabilitation programs could help post-COVID patients rebuild psychological resilience and adaptive coping. Techniques such as cognitive restructuring, exposure-based strategies, mindfulness exercises, and values-oriented action planning—core components of these models—can directly target maladaptive cognitions, emotional dysregulation, and avoidance behaviors commonly observed after severe illness [59,60]. Our study contributes to the literature by documenting a viable intervention, going beyond simply documenting the prevalence of psychiatric sequelae. This clearly justifies the need for healthcare systems to integrate psychological interventions such as CBT into rehabilitation programs for patients recovering from severe viral illnesses. This intervention has the potential to improve mental health outcomes and functional recovery.

4.3. Limitations

This study has some limitations. First, this study was conducted in a single center with a very small sample size. This limits statistical power and reduces the generalizability of the findings. Second, causal inferences regarding the effects of CBT cannot be established due to the absence of a control group. Third, some participants discontinued the intervention, which may have introduced attrition bias. Fourth, the intervention consisted of only six sessions, which may have been insufficient to produce lasting changes in mental health outcomes. In addition, the short follow-up period limits conclusions regarding the durability of the improvements. Fifth, the use of subjective self-report instruments to assess symptoms. These tools may not fully capture the complexity of patients’ experiences or the effects of psychotherapy. Finally, since participation was voluntary, selection bias cannot be ruled out. Individuals who were more motivated to seek psychological care may have been overrepresented.

4.4. Future Directions

Early interventions are crucial to combat psychiatric manifestations in post-COVID-19 patients. They should aim to improve the functional capacity and QoL of affected individuals, in addition to reducing the chances of developing neurocognitive deficits. Thus, it is essential to develop strategies for cognitive and behavioral changes during isolation, treatment in a hospital environment, and/or treatment in the ICU. This may address the fear of death and negative beliefs that complicate treatment after hospital discharge, and contribute to impotence and irritability.

Future studies should address some of the limitations of this study. First, larger and more diverse samples are needed to strengthen the external validity of the findings and to clarify the generalizability of CBT for post-COVID-19 patients across different cultural and sociodemographic contexts. Second, randomized controlled trials comparing CBT with other therapeutic approaches such as pharmacological treatment, supportive counseling, or integrative rehabilitation programs would provide a better understanding of the relative efficacy of each modality. Third, long-term follow-up is required to assess the persistence of therapeutic gains in anxiety, depression, PTSD, and QoL. Finally, future research should explore how CBT protocols can be adapted or optimized for patients with severe or prolonged symptoms and for those with comorbidities to enhance treatment outcomes and contribute to the development of evidence-based guidelines for mental health rehabilitation in post-COVID-19 populations.

5. Conclusions

Although the literature has extensively documented the prevalence of psychiatric sequelae following COVID-19, few studies have evaluated the impact of structured psychotherapeutic interventions in post-COVID-19 populations. The results of this study suggest that CBT may reduce symptoms of anxiety, depression, and PTSD. However, in light of the study’s limitations, these findings should be viewed as preliminary.