Inflammatory markers and pulmonary function in adolescents and young adults 6 months after mild COVID-19

Abstract

Introduction: Both public and scientific attention have shifted from the acute COVID-19 illness to the chronic disability experienced by a proportion of COVID-19 convalescents. Post COVID-19 condition, a term used for long-lasting symptoms after COVID-19, can affect individuals across all disease severity and age groups. Data on post-COVID-19 symptomatology, epidemiology and pathophysiology in adolescents and young adults are scarce. To date, little is known on the immunological and pulmonary trends in these patients after COVID-19. This study investigated immunological markers and pulmonary function in non-hospitalized patients in this group at 6 months after initial mild COVID-19 infection.

Methods: Non-hospitalized SARS-CoV-2 positive (n = 405) and SARS-CoV-2 negative (n = 111) adolescents and young adults (aged 12-25 years) were followed prospectively for six months after SARS-CoV-2 PCR testing. At baseline and at six months follow-up, all participants underwent an assessment including clinical examination, questionnaires, spirometry, and blood sampling. Cross-sectional comparisons of blood biomarkers; including white blood cell counts, CRP, GDF-15, a 27-multiplex cytokine assay, complement activation products and SARS-CoV-2 antibodies; and spirometry measures were performed after classification of all participants according to their COVID-19 status and adherence to post-COVID-19 case criteria. Associations between biomarkers and COVID-19 symptoms were explored.

Results: No difference in pulmonary function was detected between the groups. COVID-19 convalescents had higher levels of chemokines eotaxin, MCP-1 and IP-10 than non-infected controls. The increase was modest and not associated with long-lasting COVID-19 symptoms.

Discussion: Elevated inflammatory mediators were found in adolescents and young adults six months after mild COVID-19, but there was no association with post-COVID-19 condition.

Keywords: COVID-19; Long Covid; Post-COVID-19; adolescent; biomarker; cytokine; immunology; pulmonary function.

Figure 1

Elevated levels of cytokines at six months following COVID-19. Post hoc analysis for cytokines with significant differences between post COVID-19 condition (PCC) groups shows (A) higher levels of MCP-1° and (B) higher levels of eotaxin* in the COVID+ PCC+ and COVID+ PCC- groups compared to participants in the COVID- PCC+ and COVID- PCC- groups at 6 months. °Based upon pairwise comparison of means with Bonferroni adjustment for test multiplicity; *based on Dunn’s test for pairwise comparisons with Benjamini-Hochberg adjustment for test multiplicity; p-values indicate comparisons rejected by these methods at the alpha level (two sided tests); MCP, monocyte chemotactic protein; n.s., non-significant.

Figure 2

Elevated levels of cytokines at six months following COVID-19. Post hoc analysis for cytokines with significant differences between post-infective fatigue syndrome (PIFS) groups shows (A) higher levels of MCP-1° and (B) higher levels of eotaxin* in the COVID+ PIFS+ and COVID+ PIFS- groups compared to participants in the COVID- PIFS+ and COVID- PIFS- groups at 6 months. ° Based upon pairwise comparison of means with Bonferroni adjustment for test multiplicity; * based on Dunn’s test for pairwise comparisons with Benjamini-Hochberg adjustment for test multiplicity; p-values indicate comparisons rejected by these methods at the alpha level (two sided tests); MCP, monocyte chemotactic protein; n.s., non-significant.

Figure 3

Higher levels of (A) MCP-1°, (B) eotaxin*, and (C) IP-10° were detected in the COVID-19 positive group compared to participants in the COVID-19 negative group at six months following COVID-19 infection. ° based upon Mann Whitney U with Benjamini Hochberg correction for multiple testing; * based upon Student T test with Benjamini Hochberg correction for multiple testing; p-values indicate comparisons rejected by these methods at the alpha level (two sided tests); IP, interferon gamma induced protein; MCP, monocyte chemotactic protein.