The Inversion of IL-6 Levels in Relation to C-Reactive Protein as the Marker for Cytokine Storm Syndrome in COVID-19

Background: The SARS-CoV-2 pandemic emerged as the cause of a life-threatening severe acute respiratory syndrome (SARS) disease triggered by a remarkable and uncontrolled pulmonary inflammation known as a “cytokine storm”. This cytokine storm includes fever, coagulopathy, and sharp elevations in acute phase responses (interleukin 6, ferritin, and C-reactive protein).Methods: This study was a longitudinal clinical-based monitoring and dosing of 5 laboratory markers (C-reactive protein, IL-6, fibrinogen, ferritin and D-dimer) carried out in Porto Velho, Rondônia State, in the western Brazilian Amazon with healthy professional soon after they have been diagnosed with COVID19. The medical team of the Multidisciplinary Home Medical Care Service (HMCS) of the Department of Health of the state of Rondônia carried out the telemonitoring and, when necessary, carried out face-to-face visits. The daily follow-up with markers helped to guide the treatment of COVID-19, which was also personalized at home by a HMCS nursing team that collected vital signs and administered medications.Findings: The dairy longitudinal follow-up of inflammatory markers was used to classify early the risk of potential severity of COVID-19 between who developed definitely the cytokine storm from others whose had mild febrile syndrome. The dynamics of inflammatory markers showed among patients with febrile syndrome and altered markers, increases in CRP and IL-6 levels, and the peak of CRP mg/L was proportionally higher than the peak of IL-6 in pg/mL. Those who symptoms evolve and did not resolve infection with antibiotic therapy had alteration in the fibrinogen levels and were treated with anticoagulant and broad-spectrum antibiotics, which resolved the infection in several of them. Nonetheless, patients who developed definitely cytokine storm, despite of this treatment some days after. This moment was when IL-6 levels increased earlier than those of CRP and ferritin, which was characterized by the peak of IL-6 in pg/mL was proportionally higher than the peak of CRP mg/L. The treatment based on three pillars: antibiotic therapy, anticoagulant therapy and pulse therapy administration.Interpretation: Our findings demonstrate that IL-6, C-reactive protein, fibrinogen and ferritin were sufficient to define the timing of the evolution of cytokine storm syndrome and prevented the progressive deterioration of the lung injury. The administration of antibiotic therapy, anticoagulant therapy and pulse therapy resolved the infection for those with potential for severe COVID-19 and showed themselves to be very effective in reducing the risk of death Funding Information: Rondônia State Health Department Budget.Declaration of Interests: The Healthy Secretariat of Rondônia State provided the costs for Multidisciplinary Home Care Service, supplies and medicines. The latter were provided by the Management and Pharmaceutical Assistance Coordination (CGAF). The State Laboratory for Pathologies and Clinical Analysis from Rondônia State (LEPAC) provided laboratory markers for monitoring patients during subsequent daily follow-up. All other authors declare no competing interests.Ethics Approval Statement: The study was approved by the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado Ethics Review Board (CAAE: 51963021.9.0000.000) and the requirement for informed consent was waived by the Ethics Commission because these data come from medical and laboratory assistance that took place between 2020 and 2021 and medical records were available anonymously encoded.