Keywords: COVID-19, proteomics, inflammation, immune response,
athletes
To the Editor
Coronavirus disease 19 (COVID-19) is an infectious disease transmitted
mainly through aerosol spread of severe acute respiratory syndrome
coronavirus-2 (SARS-CoV-2) and in most cases leads mild to moderate
respiratory illness, which usually resolves within 5-7
days.1 Regular moderate-to-vigorous exercise has been
associated with a strong and timely immune response against infections,
thus reducing susceptibility to acute respiratory illness, and also
protecting from severe COVID-19 outcomes.2,3 Frequent
high intensity training has also been proposed to enhance
vaccine-induced cellular and humoral immunity.2However, long-term high-intensity physical activity and stressors
associated with elite sports (e.g., environmental, psychological) might
cause hyperinflammation in some individuals and increase the risk of
respiratory illness, and ice hockey players are among those winter sport
athletes, who have the highest incidence in that
context.3,4 Proteomic profiling of COVID-19 patients
has proven valuable in the discovery of novel biomarkers associated with
disease susceptibility, course, complications and
severity,5 but so far there are no reports of COVID-19
proteomic studies in athletes. Herein, we examined the
immune-inflammatory proteome of elite ice hockey players before and
after a team-wide COVID-19 outbreak with the omicron BA.1 variant in
December 2021.
Serum blood samples and questionnaire data were obtained from 24 players
of a Swiss National League ice hockey team 3 months prior to COVID-19
and from the same players within 1-2 weeks after nasal swab
PCR-confirmed SARS-CoV-2 infection, and of 20 controls, that are non-ice
hockey players after recent recovery from COVID-19. Written informed
consent was obtained from all study participants, and the protocol was
approved by the responsible ethics committee (Kantonale Ethikkommission
Zürich, Ref. 2019-02002). Proximity extension assay (PEA) technology by
OLINK was used for targeted proteomic serum analyses of 180 proteins
measured in the OLINK immune response and inflammation panels (92
proteins each, 4 overlaps). Immune-inflammatory profiles of ice hockey
players were compared at two time points (pre- and post-COVID-19).
Additionally, post-COVID-19 profiles of ice hockey players were compared
to the post-COVID-19 control group for reference.
Ice hockey players and control subjects reported comparable rates of
previous SARS-CoV-2 infections, atopic comorbidities (asthma, allergic
rhinitis), regularly occurring upper respiratory tract infections
(URTI), fever and recurrent herpes labialis (Table 1). COVID-19
vaccination history did not differ between athletes and controls.
Control subjects reported a higher prevalence of symptoms in general,
and respiratory symptoms specifically.
PEA-based proteomic analyses of serum samples from elite ice hockey
players identified 28 differentially expressed proteins, involved in
immune response and inflammation (Figure 1, A and D), with a rather
distinct representation of biological process networks. While similar
networks were found to be present at both sampling time points,
specifically, lymphocyte proliferation (CXCL12, CD40, PRKCQ,
TNFSF14 pre-COVID-19 and TRAF2, IRAK4, CASP-8 post-COVID-19) and
innate inflammatory response (PRKCQ, IRAK1 pre-COVID-19 and ofTRAF2, IRAK4 post-COVID-19) (Figure 1, E and F), the
post-COVID-19 profile was uniquely marked by an increase in proteins
involved in innate immune response to viral infection, neutrophil
activation, IL-12/-15/-18 and IFNγ-signaling (Figure 1, F). This last
finding therefore may reflect how the immune system responds efficiently
to COVID-19, where a timely release of antiviral interferons seems to be
essential.3
In our principal component analysis (PCA), while we could clearly
separate athletes pre- and post-infection (Figure 1, B), post-COVID-19
comparison of ice hockey players with post-COVID-19 samples of the
control non-ice hockey players group revealed similar proteomic
patterns, with only CCL11 showing a significantly higher
expression in the control group (Figure 1, C). Of note, levels ofCCL11 have recently been found to be elevated in patients
experiencing cognitive symptoms (”brain fog”) after mild COVID-19
compared to those without such symptoms.6 However, we
did not assess incidence of post- or long-COVID-19 symptoms in our
cohorts.
To conclude, we found that immune-inflammatory proteomic profiles in
serum of elite ice hockey players differ significantly pre- and
post-COVID-19. The cause for this observation might be multifactorial,
e.g., direct impact of the recent SARS-CoV-2 infection, seasonal
changes, or training-related influences on sampling timepoints. Although
proteomic profiles generally did not differ between athletes and control
subjects post-COVID-19, the higher incidence of symptomatic disease in
the control group warrants follow-up studies to investigate the
potential impact of athletic workloads on (SARS-CoV-2) infection
susceptibility, disease course and vaccination response, as well as to
identify associated biomarkers.