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. 2024 Mar 14:11:1295026.
doi: 10.3389/fnut.2024.1295026. eCollection 2024.

Post-COVID-19 condition: systemic inflammation and low functional exercise capacity

Gabriela Salim de Castro  1 , Leonardo R Gama  2 , Alexandre Ferreira Ramos  2   3 , Guilherme Gatti da Silva  1 , Alexandre Abilio de Souza Teixeira  4 , Edecio Cunha-Neto  5   6 , Heraldo Possolo de Souza  7 , Suely K Marie  8 , Leda L Talib  9 , Verônica Coelho  6   10 , Jorge Kalil  6   10 , Adriana Ladeira de Araujo  11 , Ana Paula Ritto  11   12 , Alessandro Rodrigo Belon  1 , Amanda Soares Santos  1 , Ana Paula Noronha Barrére  1 , Márcio V Y Sawamura  13 , Celina Almeida Lamas  14 , Bruno Guedes Baldi  14 , Carlos R R Carvalho  14 , Leslie Domenici Kulikowski  9 , Rodolfo Furlan Damiano  15 , Marta Imamura  16 , José Cesar Rosa Neto  4 , Fabio S Lira  17 , José Pinhata Otoch  1   18 , Euripedes Constantino Miguel  8 , Linamara Battistella  19 , Orestes V Forlenza  15 , Geraldo Busatto  11   15 , Marilia Seelaender  1
Affiliations

Post-COVID-19 condition: systemic inflammation and low functional exercise capacity

Gabriela Salim de Castro et al. Front Nutr. .

Abstract

Introduction: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported.

Methods: In this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6-12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment.

Results: SRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-α2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1β serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.

Keywords: COVID-19; PASC; cytokines; fatigue; inflammation; long COVID; post-COVID-19 condition; post-acute sequelae of SARS-CoV-2 infection.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Signs and symptoms in the follow-up assessment. Data are presented as the percentage of patients in the group. (A) Loss of Smell; (B) Loss of Taste; (C) Loss of Appetite; (D) Headache; (E) Depression; (F) Hearing Loss. Comparisons were performed using the Chi-squared test. SR, Self-Reported Symptoms group; SRPF, Self-Reported Symptoms and decreased Pulmonary Function group.
Figure 2
Figure 2
Signs and symptoms at hospital admission. Data are presented as the percentage of patients in the group. (A) Loss of Smell; (B) Loss of Taste; (C) Cough; (D) Fever; (E) Dyspnoea; (F) Muscle Aches. Chi-squared test was used to compare frequencies. SR, Self-Reported Symptoms group; SRPF, Self-Reported Symptoms and decreased Pulmonary Function group.
Figure 3
Figure 3
Serum cytokines. (A) Interferons and interleukins. (B) Growth factors and chemokines. Comparisons were performed using the Kruskal-Wallis test followed by Dunn’s post-hoc test after adjustment by days to follow-up assessment. *q value <0.052; ** adjusted value of p < 0.05. (a) Serum BDNF unit: ng/dL. BDNF brain-derived neurotrophic factor; CCL11 C-C motif chemokine ligand 11 (eotaxin-1); G-CSF granulocyte colony-stimulating factor; IFN interferon; IL interleukin MCP1 monocyte chemoattractant protein 1; MIP macrophage inflammatory protein; SR, Self-Reported Symptoms group; SRPF, Self-Reported Symptoms and decreased Pulmonary Function group.
Figure 4
Figure 4
Content of BDNF, CCL11, haemoglobin, and lymphocyte count after sex stratification. (A) Serum BDNF. (B) Serum CCL11. (C) Blood haemoglobin. (D) Serum CRP. Comparisons were performed using the Kruskal-Wallis test followed by Dunn’s post-hoc test after adjustment by days to follow-up assessment. ⟡, ⟡⟡q value <0.063; ⟡⟡adjusted value of p < 0.05. BDNF brain-derived neurotrophic factor; CCL11 C-C motif chemokine ligand 11 (eotaxin-1); CRP, C-reactive protein; SR, Self-Reported Symptoms group; SRFF, Self-Reported Symptoms and decreased Pulmonary Function group.
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