Background

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led not only to acute morbidity but also to significant long-term health consequences in a subset of those infected. The condition known as post-COVID syndrome (PCS) or "Long COVID" is characterized by a wide range of persistent or newly emerging symptoms that can persist for months or even years after the initial infection. According to WHO estimates, approximately 6% of those infected develop PCS, although meta-analyses of data show that the global prevalence may be higher, reaching 45%, with symptoms persisting for 1-2 years or more after infection [1, 2]. The growing number of people suffering from long-term symptoms places a significant burden on the healthcare system and society as a whole. Of particular concern is the fact that post-COVID syndrome can develop in people of any age, regardless of the severity of the infection and the presence of chronic diseases, as well as in individuals who had asymptomatic COVID-19. Women, the elderly, patients with obesity, chronic diseases, and those who experienced a severe course of the disease are considered the most vulnerable [3-5].

"Long COVID" manifests with multiple symptoms, including debilitating weakness (fatigue), shortness of breath, cognitive impairment ("brain fog"), muscle and joint pain, sleep disturbances, and various neurological and psychological problems [6, 7]. These symptoms can seriously affect people's daily lives, their ability to work, and their overall quality of life. Despite recognition of the seriousness of the problem, significant gaps remain in understanding the mechanisms of PCS development, risk factors, and long-term prognosis.

Given the ongoing circulation of SARS-CoV-2 and the emergence of new viral variants, as well as the high prevalence of PCS and its impact on public health, conducting research aimed at identifying new clinical phenomena, features of the course, and factors influencing the duration and severity of symptoms is extremely relevant. Such data are necessary for the development of effective diagnostic, treatment, and rehabilitation programs, as well as for optimizing patient routing and forming personalized recommendations for recovery after COVID-19.

Objective

To analyze the features of long-term symptoms in patients who have had COVID-19, based on survey data, in order to identify new clinical phenomena, determine the frequency and duration of their manifestations, as well as to study the influence of demographic and clinical factors on the formation of post-COVID syndrome.

Materials and methods

For the study, data from a 2024 survey were used, collected using a specially designed electronic questionnaire intended to assess long-term symptoms in patients who had recovered from COVID-19. The study involved 220 respondents, residents of Yaroslavl, of which 82.7% were women (n=182) and 17.3% were men (n=38). The age of participants ranged from 18 to 68 years, with the majority of respondents aged between 20 and 45 years. The mean age was M=33.8; SD=10.1 years. A significant portion of participants were young adults aged 20-30 years, with a gradual decrease in the number of respondents in older age groups. This distribution allows characterizing the long-term symptoms of COVID-19 primarily within the context of a young and adult population. The questionnaire collected information on the presence of chronic diseases, vaccination status, as well as symptoms of the disease and duration of illness. Special attention was paid to symptoms persisting after the acute phase of COVID-19, including weakness, sleep disturbances, cognitive disorders, changes in smell and taste, hair loss, joint and muscle pain, and psycho-emotional manifestations. Respondents indicated the duration and nature of the symptom course.

Methods of descriptive statistics were used to process the obtained data in order to identify patterns and correlations using Stattech software (Kazan). Differences were considered statistically significant at p < 0.05. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. All participants gave informed consent to participate in the study. The data were anonymized to maintain confidentiality.

Results and discussion

The analysis of the survey data revealed key features of long-term symptoms after COVID-19 and their impact on quality of life. The age composition of the sample reflects an active socio-economic group, highlighting the significance of the post-COVID syndrome problem specifically for the working-age population.

The predominance of women in the sample and their more frequent reporting of post-COVID symptoms support the hypothesis of the influence of hormonal and immunological factors on the development of PCS. Women typically have a more active immune response, which may contribute to the development of chronic inflammation and autoimmune reactions after infection.

When studying the features of somatic status, it was found that 131 respondents (59%) reported no chronic diseases. Among those who did, the most common were obesity (14), autoimmune diseases (11), and bronchial asthma (7). Correlation analysis showed that the presence of chronic diseases is associated with a high probability of prolonged weakness (χ² = 9.3, p=0.001). A wave-like course of symptoms was more characteristic of individuals with autoimmune diseases and obesity (χ² = 8.7, p=0.005).

Vaccination, although it reduced the severity of the acute phase, did not always completely prevent the development of post-COVID syndrome, which is consistent with international observations. 39% of respondents were not vaccinated against COVID-19; the rest received various vaccines, predominantly "Sputnik V" (89.6%). Vaccinated respondents less frequently reported severe respiratory disorders and depressive states, which is consistent with data on the protective effect of vaccination (p <0.05).

The results confirmed the multisystemic nature of PCS: the majority of participants retained various symptoms affecting the nervous, respiratory, musculoskeletal, and psycho-emotional spheres. The most frequently reported were fatigue and weakness (83.8%), cognitive impairment -- problems with memory and concentration (over 50%), insomnia (35%), depressive states (52.4%), and hair loss (52.1%). These data correlate with the results of international studies, where fatigue and cognitive impairment ("brain fog") are recognized as dominant manifestations of Long COVID.

The main symptoms and their frequency of occurrence in patients who had COVID-19 are reflected in Table 1.

Table 1. Prevalence of the main symptoms in patients with COVID-19, %

SymptomAbsolute number%Increased sleepiness12258.4Increased sweating8942.4Fatigue17683.8Respiratory disorders (congestion, cough, shortness of breath)8942.4Depressive states (mood changes, tearfulness)11052.4Aggressiveness6731.9Panic attacks5124.2Memory problems11454.5Difficulty concentrating11755.7Hair loss11052.1Joint pain9846.4Headaches11554.5

The high level of psycho-emotional symptoms -- depression, anxiety, and panic attacks -- is particularly noteworthy, consistent with data on the increased frequency of psychiatric disorders after COVID-19, including post-traumatic stress disorder (PTSD) and sleep disorders. This underscores the need to integrate psychiatric support into rehabilitation programs.

The duration of symptoms varied from several weeks to several years, with more than half of respondents noting symptom persistence for over three months (Table 2).

Table 2. Duration of weakness retention in patients with COVID-19

Duration of weaknessNumber of respondents (absolute number)Up to 1 week321-3 weeks533 weeks -- 2 months42More than 2 months37No weakness46

A wave-like course -- where symptoms disappear and reappear -- was characteristic of 65% of participants. This phenomenon complicates diagnosis and patient management, requiring an individual approach and long-term monitoring. Comparison with international data shows that the wave-like nature and intermittent relapses of symptoms are a typical feature of PCS, associated with multifactorial pathogenesis, including immune imbalances, chronic inflammation, and autonomic nervous system disorders.

Prolonged loss or distortion of smell and taste, as well as the appearance of strange odors (parosmia), were noted in a significant proportion of respondents (85%), sometimes persisting for over a year. Some respondents reported paradoxical hypersensitivity to odors: 7% of patients noted not only loss but also increased sensitivity to certain smells, accompanied by headache and nausea. Alongside the well-known olfactory (parosmia, hyposmia) and gustatory disturbances, the study identified cases of selective aversion to specific foods (meat, chicken, seafood, sweets) in individual respondents. Most often, patients reported a persistent aversion to meat (20.5%), chicken (17.3%), seafood (10.0%), sweets (6.8%), and even fresh fruits and vegetables (4.5%). This phenomenon was observed regardless of the presence of classical taste or smell disorders. Patients with aversion to meat and chicken more often noted prolonged weakness (χ² = 9.8, p=0.002), and also more frequently complained of weight loss (r=0.32, p=0.01). This indicates a potential impact of sensory disturbances on nutritional status and recovery. It is important to note that this aversion is not always associated with a distortion of the smell or taste of the product itself, but rather with a kind of subconscious rejection, which may be related to changes in the functioning of the limbic system and its influence on eating behavior. This observation, requiring further study, may be important in developing dietary recommendations for patients with PCS.

Although skin manifestations in COVID-19 and PCS are fairly well studied, our sample included isolated cases of atypical rashes accompanied by signs of microcirculatory disorders (livedo reticularis, petechiae). Fifteen respondents (6.8%) reported the appearance of atypical skin rashes, including livedo reticularis, petechiae, and local edema; another 11.4% described vasculitis-like manifestations. Given that these patients had a history of autoimmune diseases, a link between COVID-19-associated vasculitis and unusual skin manifestations can be hypothesized. Interestingly, 60% of patients with skin manifestations had autoimmune or metabolic comorbidities, which was statistically significantly more frequent than in the group without skin symptoms (χ² = 7.2, p=0.007), as reflected in the figure.

Fig. The relationship of skin manifestations with concomitant diseases, %

This aspect requires further in-depth study with the involvement of dermatologists and rheumatologists.

An interesting observation was the indication by some respondents of the appearance of unusual reactions to medications after recovering from COVID-19.

Thirty people (13.6%) began to notice unusual side effects to familiar medications for the first time after the infection: nausea after a week of taking pills, a change in the taste of medications, a feeling of "teeth clenching" when taking pills. This fact may indicate changes in drug metabolism related to the virus's effect on the liver and other organs. Patients with new drug reactions were more likely to have concomitant liver disorders (by history) and complained of prolonged weakness (r=0.28, p=0.03). This underscores the need for caution when prescribing therapy in the post-COVID period. The possibility of such reactions must be considered when prescribing drug therapy to patients who have had COVID-19, and side effects should be carefully monitored.

Cognitive impairment in more than half of the respondents, including "brain fog," memory problems, and difficulty concentrating, indicates a lasting impact of COVID-19 on brain function. Mechanisms may include microvascular disorders, chronic inflammation, and autoimmune processes.

Among the factors provoking symptom relapses, patients most often cited stress (31.8%), weather changes (22.7%), and changes in daily routine (18.2%). 27.3% noted no obvious provoking factors. In the group noting the influence of stress, panic attacks and insomnia were more common (χ² = 8.9, p=0.004), and with weather changes -- joint pain and skin manifestations (χ² = 6.2, p=0.013).

Emergence of new food allergies: 4% encountered, for the first time after COVID-19, allergic reactions to foods previously well tolerated.

About 10% described episodes of "feeling hot" or "chills" without an objective rise in temperature, which correlated with anxiety disorders (r=0.29, p=0.02).

Conclusion

Post-COVID syndrome is characterized not only by prolonged physical and cognitive disorders but also by unique sensory, skin, and food-related phenomena. Selective aversion to foods and new food allergies can significantly affect nutritional status and require an individualized approach to diet and support. Atypical skin manifestations and vasculitis-like reactions are more common in patients with autoimmune and metabolic diseases, justifying the need for interdisciplinary observation. Unusual drug reactions after COVID-19 require caution when prescribing therapy and dynamic monitoring. The wave-like nature of symptoms and their association with psychosocial and meteorological factors highlight the importance of comprehensive rehabilitation considering individual triggers. The obtained data expand the understanding of post-COVID syndrome and can serve as a basis for the development of new clinical guidelines for the diagnosis, treatment, and rehabilitation of patients after COVID-19.