Different cytokine and chemokine profiles in hospitalized patients with COVID-19 during the first and second outbreaks from Argentina show no association with clinical comorbidities

Abstract

BackgroundCOVID-19 severity has been linked to an increased production of inflammatory mediators called “cytokine storm”. Available data is mainly restricted to the first international outbreak and reports highly variable results. This study compares demographic and clinical features of patients with COVID-19 from Córdoba, Argentina, during the first two waves of the pandemic and analyzes association between comorbidities and disease outcome with the “cytokine storm”, offering added value to the field.MethodsWe investigated serum concentration of thirteen soluble mediators, including cytokines and chemokines, in hospitalized patients with moderate and severe COVID-19, without previous rheumatic and autoimmune diseases, from the central region of Argentina during the first and second infection waves. Samples from healthy controls were also assayed. Clinical and biochemical parameters were collected.ResultsComparison between the two first COVID-19 waves in Argentina highlighted that patients recruited during the second wave were younger and showed less concurrent comorbidities than those from the first outbreak. We also recognized particularities in the signatures of systemic cytokines and chemokines in patients from both infection waves. We determined that concurrent pre-existing comorbidities did not have contribution to serum concentration of systemic cytokines and chemokines in COVID-19 patients. We also identified immunological and biochemical parameters associated to inflammation which can be used as prognostic markers. Thus, IL-6 concentration, C reactive protein level and platelet count allowed to discriminate between death and discharge in patients hospitalized with severe COVID-19 only during the first but not the second wave.ConclusionsOur data provide information that deepens our understanding of COVID-19 pathogenesis linking demographic features of a COVID-19 cohort with cytokines and chemokines systemic concentration, presence of comorbidities and different disease outcomes. Altogether, our findings provide information not only at local level by delineating inflammatory/anti-inflammatory response of patients but also at international level addressing the impact of comorbidities and the infection wave in the variability of cytokine and chemokine production upon SARS-CoV-2 infection.

COVID-19 patients display changes in lymphocyte subsets with a higher frequency of dysfunctional CD8lo T cells associated with disease severity

“…It is well known that Treg maintains immune homeostasis and prevents immunopathology in viral infections ( 50 – 52 ). In agreement, the reduced frequency of circulating Treg in patients with severe disease in our cohort matches the high levels of cytokines and chemokines we previously described in first wave hospitalized patients ( 20 ). The pro-inflammatory environment and the triad of high systemic levels of IP-10, IL-10, and IL-6 depicted in severe patients from the first COVID-19 wave from Argentina ( 20 ) have been reported in other cohorts, also occurring with a reduced frequency of circulating Treg ( 53 ).…”

“…In agreement, the reduced frequency of circulating Treg in patients with severe disease in our cohort matches the high levels of cytokines and chemokines we previously described in first wave hospitalized patients ( 20 ). The pro-inflammatory environment and the triad of high systemic levels of IP-10, IL-10, and IL-6 depicted in severe patients from the first COVID-19 wave from Argentina ( 20 ) have been reported in other cohorts, also occurring with a reduced frequency of circulating Treg ( 53 ). Mechanistically, Treg depletion may be a component of lymphopenia caused by apoptosis or extravasation into inflamed tissue, but it also may be a consequence of a direct inhibitory effect of proinflammatory cytokines, such as IL-6, on Treg differentiation ( 52 , 54 ).…”

“…To this end, we first performed a linear discriminant analysis (LDA) of the parameters measured in the three groups of donors of the entire cohort. Then, we calculated the apparent error rate (AER) when three commonly used laboratory biomarkers, such as neutrophil counts, C-reactive protein (CRP), and IL-8, were used to discriminate among the three groups ( 20 ). In this case, the AER was 29.1%, a value that is not significantly acceptable.…”

“…Patients with pre-existent comorbidities such as diabetes, arterial hypertension, asthma, overweight, heart disease, dyslipidemia, hypothyroidism, and obesity were included. The demographic features, laboratory, clinical characteristics, and cytokine and chemokine serum concentrations of hospitalized COVID-19 patients were reported in an our previous report using the same cohort of patients ( 20 )…”

“…Additionally, we observed that concurrent pre-existing comorbidities do not significantly contribute to the higher levels of systemic cytokines and chemokines in these patients. In addition, we detected that patients recruited during the second wave of infection were characterized by a younger age and a lower prevalence of concurrent comorbidities compared to those from the first outbreak ( 20 ).…”