This study revealed that nearly one-fourth of hospitalized COVID-19 patients reported persistent physical, cognitive, and/or psychological symptoms at 3 and 12 months postdischarge. Only anxiety levels significantly decreased in the first year after discharge. Higher numbers of physical, cognitive, and psychological symptoms 12 months postdischarge were associated with premorbid conditions (chronic respiratory disease, higher CCI), illness severity (being infected during the third wave), physical variables (COVID-19-related pulmonary abnormalities, lower TLC, dyspnoea), and cognitive and psychological variables (cognitive symptoms, anxiety, depressive symptoms, and PTSS levels). Furthermore, a higher number of persistent symptoms at 12 months was associated with higher levels of rumination, catastrophizing, and acceptance as well as lower levels of positive refocusing, putting things into perspective, and a higher number of physical symptoms at three months.

Despite a significant decrease in anxiety symptoms over time, a substantial proportion of patients continued to experience clinically significant levels of anxiety, depression, and PTSS at T1 and T2, with prevalence rates ranging from 15 to 22%. In the literature, there is inconsistency in these rates, with some studies finding similar rates of psychological symptoms⁴²and others finding higher rates. For example, compared with nonhospitalized patients who completed similar measures⁴³, the prevalence of psychological symptoms in the present study was lower but remained higher than that in the general population before the COVID-19 pandemic^44,45. In this study, patients were invited to the COVID-19 clinic regardless of symptoms, while in previous studies, patients were often included due to the presence of persistent symptoms^43,46.

Similar prevalence rates of cognitive symptoms have been reported in other studies. A meta-analysis of 43 studies involving both hospitalized and nonhospitalized patients revealed that approximately one in five COVID-19 patients reported cognitive symptoms 12 or more weeks after infection⁴⁷. However, these symptoms and related cognitive difficulties do not necessarily indicate the presence of cognitive impairment. Klinkhammer et al.⁴²reported that 8–10 months postdischarge, 62% of ICU and general ward COVID-19 survivors reported three or more cognitive symptoms, whereas standard neuropsychological testing revealed cognitive dysfunction in only 12% of patients. Moreover, approximately one-third of the patients reported moderate to severe physical symptoms, which is consistent with findings of a review on post-COVID-19 physical symptoms⁴. These symptoms resemble chronic symptoms after other viral infections. Similar to post-COVID-19 condition, after viral infections, the majority of patients completely recover within several weeks, whereas a small subgroup experiences persistent sequelae. The cognitive behavioural model of chronic fatigue syndrome (CFS) may offer an explanatory framework for how chronic symptoms can develop through reciprocal interactions among physiology, cognition, emotion, and behaviour after a viral infection⁴⁸.

The current study identified several prognostic factors associated with physical, cognitive, and psychological functioning twelve months postdischarge. Notably, preexisting chronic respiratory disease emerged as a significant predictor of these symptoms. Similarly, a recent meta-analysis revealed that chronic respiratory diseases, including asthma and COPD, are associated with persistent long-term symptoms following COVID-19¹². Moreover, patients with COPD generally experience higher levels of cognitive impairment and psychological distress (i.e., anxiety and depression) than the general population, which may, in turn, contribute to a greater risk of long-term symptoms post-COVID-19^38,39,40.

While age and sex were not associated with persistent symptoms in the present study, other demographic factors, such as cognitive reserve and lifestyle, have been shown to influence long-term outcomes after COVID-19 infection. For example, Costas-Carrera et al.⁴⁹ reported that cognitive reserve moderated cognitive function in post-ICU patients after severe COVID-19 infection, with greater cognitive reserve providing a protective effect against cognitive impairments. Similarly, Devita et al.⁵⁰reported that cognitive reserve served as a protective factor against psychological distress in COVID-19 survivors one month after hospital discharge. These findings suggest that cognitive reserve may moderate the impact of the disease at different levels. In contrast, an unhealthy lifestyle, characterized by physical inactivity and poor dietary habits, has been associated with a higher risk and prolonged duration of post-COVID-19 condition^51,52,53. Reduced physical activity levels in individuals with post-COVID-19 condition have been associated with negative psychological outcomes, including diminished self-esteem, heightened frustration, and feelings of guilt^54,55, while maintaining an active lifestyle appears to have a protective effect⁵². Furthermore, diets high in saturated fats and low in nutrient-rich foods may further increase the risk of developing post-COVID-19 condition⁵³.

Among the illness severity variables, only the infection wave was significantly associated with the outcome. Patients infected with COVID-19 during the third wave (predominantly the beta/gamma variant) reported more long-term physical, cognitive, and psychological symptoms than did those infected during the first wave (wild-type variant). While this finding may suggest that the beta/gamma variant leads to more severe long-term symptoms, it is important to note that infection wave was measured indirectly based on the time of admission rather than confirmed variant identification. There are inconsistent findings in the literature regarding the influence of infection waves on outcomes. Some studies suggested that the wild-type variant (first wave) is more strongly associated with severe COVID-19 symptoms, whereas other studies indicated that later waves (Beta/Gamma/Omicron variants) are linked to greater disease severity^56,57. Given these inconsistencies, our findings, alongside existing research, underscore the need for further investigation to clarify the relationship between COVID-19 variants and long-term symptoms. This is particularly relevant, as our study was unable to directly determine the variant, limiting the ability to establish a precise association.

There are also inconsistent findings regarding the severity of acute infection as a potential risk factor for long-term outcomes. A meta-analysis of 10 studies revealed that patients who required ICU admission during the acute phase of SARS-CoV-2 infection had more than twice the risk of developing persistent symptoms compared with those who did not require ICU admission¹². In contrast, other studies did not find an association between the severity of acute infection and long-term neurological and cognitive functioning, emotional distress, or well-being⁴². In the present study, only 18% of patients were admitted to the ICU, which may explain the absence of an association within our cohort. Notably, COVID-19 illness severity in hospitalized patients is often approximated by differentiating between ICU and general ward admissions. While this categorization provides an indication of illness severity, utilizing standardized severity scores such as the WHO COVID-19 disease severity categorization²⁷, as in the present study, can offer a more differentiated measure of disease severity, distinguishing between various levels of severity.

Among the physical symptoms assessed at three months postdischarge, both dyspnoea and fatigue were associated with physical, psychological, and/or cognitive outcomes in the models that did not include psychological or cognitive factors. However, after controlling for psychological and cognitive factors, only dyspnoea was found to be associated with physical symptoms. The lack of association between fatigue and outcomes in the final models may be explained by the overlap between fatigue and cognitive and psychological symptoms. This overlap was also observed in a recently published study, where fatigue was not associated with outcomes after controlling for other factors, such as depression⁵⁸.

The finding that TLC and COVID-19-related pulmonary abnormalities were linked to psychological outcomes contrasts with previous research, which has indicated that pulmonary function impairments and anomalies detected on chest CT scans at three months were not associated with enduring symptoms at twelve months, including cognitive impairments and physical and psychological symptoms post-COVID-19^59,60. However, in our study, the associations were only observed for depressive and PTSS symptomatology, while other lung function variables also showed no correlation with outcomes. Our contrasting findings could arguably be explained by the greater number of patients with chronic respiratory disease in our study than in other studies, potentially influencing the association between TLC impairments and depressive symptomatology. Nevertheless, these findings underscore the intricate aetiology of the multifaceted symptoms following SARS-CoV-2 infection, extending beyond the biological system.

This study confirmed the impact of psychological factors at three months postdischarge, including depression, anxiety, and PTSS, on physical and psychological symptoms at twelve months postdischarge. Moreover, the regression models revealed a considerable increase in the amount of explained variance when psychological factors were added to the models for all the outcomes. Similarly, cognitive factors at three months were associated with cognitive outcomes at twelve months. These findings are consistent with prior research indicating associations between psychological factors, such as anxiety and depression, and post-COVID-19 condition¹². Given the potential impact of acute infection on physical, cognitive, and psychological functioning, these factors may interact with each other, creating a vicious cycle in which physical, cognitive, and psychological factors reinforce each other, leading to persistent symptoms. Coping likely plays a significant role in this cycle, as has been found in other patient populations, such as those with Lyme disease, fibromyalgia, and stroke^61,62,63,64. Rumination and catastrophizing have been shown to be maladaptive strategies, whereas positive refocusing and putting things into perspective have been recognized as adaptive strategies. However, the finding that acceptance was associated with maladaptive outcomes is not consistent with previous research. Studies conducted during the pandemic in various populations have shown positive effects of acceptance strategies on quality of life, resilience, and psychological functioning^65,66. However, to our knowledge, few studies have investigated coping among formerly hospitalized COVID-19 patients⁶⁷. Acceptance reflects acknowledging the reality of the situation³⁷. A potential explanation for the negative association between acceptance and physical and psychological symptoms, as observed in the present study, is that the uncertainty of the situation during the COVID-19 pandemic may have led to feelings of hopelessness upon acceptance. It remains unclear whether patients, in addition to accepting the situation, actively committed to living according to their values and resumed daily activities. Avoidance of these activities may contribute to persistent symptoms. However, this finding requires further investigation.

In addition to coping mechanisms, personality traits such as high levels of optimism and low levels of neuroticism and pessimism may serve as protective factors against the impact of illness, as demonstrated in other diseases, such as stroke^63,64. To our knowledge, this association has not yet been explored in post-COVID-19 patients. Furthermore, previous research has shown that greater perceived social support is associated with fewer persistent psychological symptoms, such as anxiety and depression, following SARS-CoV-2 infection⁶⁸. Additional recent studies have supported these findings, demonstrating that greater perceived social support is associated with fewer depressive symptoms in hospitalized patients⁶⁷, as well as with reduced anxiety and depressive symptoms and improved quality of life on average one year after infection⁶⁹. Additionally, among ICU survivors, a lack of social support has been identified as a risk factor for psychological symptoms three months after discharge⁷⁰. These findings provide further insight into the role of psychological resources and coping mechanisms in mitigating the long-term impact of COVID-19.

The current study had several limitations. First, only patients who completed both outcome assessments were included, thus limiting the sample size. Patients who had recovered at three months may have been less inclined to return for the 12-month follow-up appointment. All hospitalized patients were invited to the clinic, and the data were registered as part of regular care to mitigate selection bias. However, the extent to which these findings can be generalized to a broader population of hospitalized post-COVID-19 patients remains unclear. Second, the findings cannot be generalized to nonhospitalized post-COVID-19 patients. Third, factors that have been shown to be associated with persistent symptoms in previous studies, such as psychiatric history, race, cognitive reserve, lifestyle, personality factors, and perceived social support, were not assessed in this study. Additionally, demographic factors were not included in further analyses, as they were not significant in the bivariate analyses. However, we acknowledge, based on current literature, that female sex is a risk factor for post-COVID-19 condition¹¹. Data collection occurred during the early stages of the COVID-19 pandemic, when studies on the associations between potential determinants and outcomes were scarce.

An inherent strength of this study is the broad spectrum of factors that were included in the analysis and the adoption of a biopsychosocial perspective in comprehending persistent sequelae post-COVID-19, which has significant clinical and research implications.

These findings underscore the persistent physical, cognitive, and psychological symptoms experienced by post-COVID-19 patients, thus highlighting the need for targeted interventions to address these sequelae. This study demonstrated that the interplay between biopsychosocial factors and symptomatology post-COVID-19 emphasizes the importance of incorporating biopsychosocial aspects into post-COVID-19 patient care. Understanding these interactions is crucial for effective interventions^9,71. Based on individualized case conceptualization that includes premorbid, physical, psychological, and cognitive factors, a personalized treatment plan can be devised. The finding that symptoms remain relatively stable over time and that early symptoms predict long-term outcomes supports the need for early screening of patients at risk of long-term problems, which could be targeted with treatment.

There is evidence supporting the effectiveness of multidisciplinary treatments that target biological, psychological, and/or social factors in alleviating post-COVID-19 symptoms. For example, a recent study demonstrated that an inpatient multidisciplinary rehabilitation programme incorporating cognitive behavioural therapy and exercise led to reduced symptom severity, improved self-efficacy, and increased activity and participation⁷². Additionally, cognitive behavioural therapy (CBT) has been shown to effectively alleviate fatigue post-COVID-19 and enhance disease coping in both a feasibility study and a randomized controlled trial^10,73. Moreover, the reduction in PTSS following rehabilitation was associated with decreased fatigue⁷⁴. Further research employing a biopsychosocial perspective is warranted to deepen our understanding of the aetiology and treatment of persistent symptoms.

In conclusion, this study underscores the persistent physical, cognitive, and psychological symptoms experienced by COVID-19 patients postdischarge and the need for targeted interventions. The biopsychosocial perspective provides insights into the complex interplay of factors influencing post-COVID-19 sequelae, emphasizing the importance of personalized interventions that focus on biological and psychological factors. These findings have implications for improving the long-term outcomes and mental health of COVID-19 survivors.