Dynamic Changes in Neutrophils Anti-Apoptic Chemokines and Cytokines Influence the Outcome of COVID-19 in Sudanese Patients

Background: SARS-CoV-2 virus is causing a global pandemic that has so far affected more than 179 million individuals with more than 3.8 million deaths. COVID-19 is an acute respiratory syndrome presented by respiratory and hematological dysfunctions with evidence of multiorgan pathology. Studies have shown that COVID-19 is marked by neutrophilia, lymphopenia, thrombocytopenia and induction of intense chemokine/ cytokine response causing cytokine storm. IL-6, IL-8 and IL-10 have been identified as biomarkers of severe COVID-19.This manuscript aimed to analyze the dynamic changes of the neutrophil and chemokine/ cytokine response in relation to outcome of COVID-19 in Sudanese COVID-19 patients.  Methods: Thirty three (33) confirmed COVID-19 patients and 8 contact controls were enrolled in this study. Fifteen patients were males. The age of the patients ranged between 23 and 86 years with mean age of 54.5, while 4 males and 4 females were enrolled as control with age range 32- 44 years. The patients were admitted as moderate or severe COVID-19 cases. Clinical and laboratory investigations were done for all participants. Twenty chemokines/ cytokines were measured in plasma samples collected at the day of admission and day 12 post-admission using microarray. The patients were followed for 4 weeks the duration of the hospitalization and were categorized into three groups according to the outcome of the management: recovered, died or developed renal complications.  The data was analyzed to determine the dynamic of the changes of neutrophils and chemokine/ cytokines in relation to the outcome of the disease.  Findings: The most frequent clinical signs were fever, cough, headache, fatigue, loss of taste and/ or smell. COVID-19 was confirmed by RT PCR, X-ray of Ct scan of the lungs. The hematology investigations showed neutrophilia, lymphopenia, thrombocytopenia, disturbed liver and renal functions. The neutrophil/ lymphocyte ratio was elevated. Analysis of the first samples showed the production of both pro and anti-inflammatory chemokines/cytokines. IL-6, IL-8 and IL-10 were elevated compared with the contact controls and were identified as biomarkers for COVID-19. During the follow up: 18 patients recovered, 11 died and 4 developed renal failure and required dialysis.  Analysis of the samples collected at Day 12 showed dynamic changes in neutrophil count, neutrophil: lymphocyte ration, and the chemokine/ cytokine levels compared with the first samples.  There was a minor decrease in neutrophil/ lymphocyte ratio specially among patients who died. There was a significant elevation of neutrophil anti-apoptic chemokines/ cytokines specially among patients who died. IL-6, IL-8 and IL-10 were markers of fatal outcome of CPOVID-19 patients, while IL-1β, IL-4 and TNFα were markers of renal impairment. Interpretation: COVID-19 is marked by elevations of neutrophil, proinflammatory chemokines/ cytokines and elevation of neutrophil anti-apoptic mediators. The data suggest a significant role of neutrophil in the severity and the outcome of CPVID-19. Elevated IL-6, IL-8 and IL-10 were biomarkers of severe and fatal outcome of COVID-19 while elevated IL-1β, IL-4 and TNFα were biomarkers of renal impairment in moderate and severe COVIUD-19 patients . Funding Information: This research was commissioned by the National institute for Health Research (NIHR) Global Health Research Programme (16/136/33) using UK AID from the UK Government. Declaration of Interests: All authors declare no competing interest in the conducted study. Ethics Approval Statement: This study received ethical approval from Khartoum State Ministry of health ethics committee. Written consents were obtained from the participants before their enrollment in the study.