key: cord-0986721-z1kdogh8
authors: Akinosoglou, Karolina; Delastic, Anne‐Lise; Dimakopoulou, Vasilina; Marangos, Markos; Gogos, Charalambos
title: Elements of Th1/Th2 response and disease severity in COVID‐19 patients: A short report
date: 2021-09-04
journal: J Med Virol
DOI: 10.1002/jmv.27313
sha: e39480e41c2f72e27948a56ce39ee4b13cd83073
doc_id: 986721
cord_uid: z1kdogh8

The presence of a complex immune dysregulation syndrome has been established in COVID‐19 patients. We aimed to assess Th1/Th2 response in COVID‐19 patients and its association with disease severity by performing a prospective cohort study in a tertiary hospital COVID‐19 referral center. We report no difference between Th1/Th2 responses between patients with severe and mild disease, except for levels of interleukin‐6 (IL‐6) and IL‐10. Future larger studies should examine lung‐specific versus systemic inflammatory responses, as well as, diverse immunotypes driving poor clinical outcomes.

patients with increased risk of severe disease and poor outcomes to ensure timely interventions.

Recent data has shown a complex immune dysregulation syndrome in COVID-19 patients-involving a number of cytokines that determines outcomes but also provides the chance of future immunomodulatory efforts. 1 However, data remains scarce and contradictory regarding Th1/ Th2 response in these patients, as this mirrored in the levels of pro and anti-inflammatory cytokines. [1] [2] [3] We hypothesize that, Th1/Th2 responses at the time of admission could predict the outcome, hence could prove a useful tool for timely and specific immunomodulatory interventions. We aimed to assess whether Th1/Th2 response differed in patients with severe disease from mild disease, hence could represent a useful marker of severity and guide further treatment.

This was a prospective study carried out in the COVID-19 ward of a referral tertiary hospital in Greece. The study protocol was approved by the Sequential Organ Assessment Score significantly differed between groups, but not values of white blood cells, C-reactive protein, or ferritin (Table 1) . No difference was noted in cytokine levels or Th1/Th2 response as this is reflected in respective cytokine ratios except for interleukin-6 (IL-6) and IL-10 levels and IL-6/IL-10 ratio (Table 1 and Figure 1 ). No difference in outcome was observed between groups.

We aimed to examine Th1/Th2 response in COVID-19 patients and their association with disease severity. We report no significant difference, except for IL-6 and IL-10 levels between groups. Previous authors have reported increased levels of IL-2, IL-10, TNF-α, IL-7, monocyte chemoattractant protein-1, granulocyte colonystimulating factor, inducible protein-1, and macrophage inflammatory protein 1-alpha in patients with SARS-CoV-2, admitted in the ICU, than those who did not need intensive care. 3 Those patients suffered increased complications, including secondary infections, acute respiratory distress syndrome (ARDS), and cardiovascular adverse events, and hence increased mortality. On the contrary, similar to our findings, a previous report did not observe significant differences between patients with mild and severe disease. 5 As also shown in our study, both IL-6 and IL-10 levels' concentrations and the respective ratios were significantly higher in patients developing more severe symptoms of COVID-19 and eventually requiring aggressive ventilation compared to those who did not. 5, 6 This comes in line with past observations, showing that their combined use exhibits nearly 100% specificity and 83.3% sensitivity for classification of patients in severe and nonsevere categories, 6 whereas IL-6/IL-10 ratio can be predictive of clinical outcome. 7 These findings suggest an enhanced Th2 response in these patients and a respective Th1 counterpart in the lockdown mode. This imbalance has been previously reported in SARS infections and is similar to that observed in influenza-infected elderly patients who represent a high-risk patient group for poor outcomes. 8 This supports the concept of "cytokine storm," in line with data from larger cohorts identifying TNF-a and IL-6 as independent predictors of disease severity. 1 However, consequent studies called this hypothesis into question, showing that inflammatory cytokine levels in the plasma of patients with COVID-19 are similar or even lower than patients with ARDS and sepsis. 9 Whether this is a result of increased viral load, rather than a dysregulated response that requires correction remains to be seen. In our study, we found no significant difference in Th1/Th2 response, as reflected in the majority of serum levels of major pro-and anti-inflammatory cytokines and their ratio, except for the IL-6/IL-10 ratio. It is possible that injurious host response may be more compartmentalized to the lung or gradually progress its way extrapulmonary in some individuals, rather than reflect an ab initio systemic cytokine storm, mirrored in cytokine plasma levels. This could explain the fact that in SARS-CoV-2 patients who do not require supplemental oxygen, dexamethasone may be harmful and the fact that in our study, irrespective of the severity of presentation, outcomes were not found to differ significantly. 

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