COVID-19 Sequelae and the Host Pro-Inflammatory Response: An Analysis From the OnCovid Registry

Background: 15% of patients with cancer experience symptomatic sequelae, which impair post COVID-19 outcomes. In this study we investigated whether a pro-inflammatory status is associated with the development of COVID-19 sequelae. Methods: OnCovid recruited 2795 consecutive patients, diagnosed with SARS-CoV-2 infection between 27/02/2020-14/02/2021. This analysis focused on COVID-19 survivors who underwent a clinical re-assessment after the exclusion of patients with haematological malignancies. We evaluated the association of inflammatory markers collected at COVID-19 diagnosis with sequelae, considering the impact of prior systemic anticancer therapy (SACT). Results: Out of 1339 patients eligible, 203 experienced at least one sequela (15.2%). Median baseline C-reactive protein (CRP, 77.5 mg/L vs 22.2 mg/L, p<.001), lactate dehydrogenase (LDH, 310 UI/L vs 274 UI/L, p=.028) and neutrophil-to-lymphocyte ratio (NLR, 6.0 vs 4.3, p=.001) were statistically significantly higher among patients who experienced sequelae, while no association were reported for platelet-to-lymphocyte ratio (PLR) and the OnCovid Inflammatory Score (OIS), which includes albumin and lymphocytes. The widest Area under the ROC curve was reported for baseline CRP (AUC 0.66,95%CI:0.63-0.69), followed by the NLR (AUC0.58,95%CI:0.55-0.61) and LDH (AUC=0.57,95%CI:0.52-0.61). Using a fixed categorical multivariable analysis high CRP (OR 2.56,95%CI:1.67-3.91) and NLR (OR 1.45,95%CI:1.01-2.10) were confirmed to be statistically significantly associated with an increased risk of sequelae. Exposure to chemotherapy was associated with a decreased risk of sequelae (OR 0.57,95%CI:0.36-0.91), while no associations with immune checkpoint inhibitors, endocrine therapy, and other types of SACT were found. Conclusions: Although the association between inflammatory status, recent chemotherapy and sequelae warrants further investigations, our findings suggest that a deranged pro-inflammatory reaction at COVID-19 diagnosis may predict for sequelae development.