Maowia M. Mukhtar, Mahgoub Monofli, Babiker M. Osman, Khabab A. Elhaj, Marc Botcherby, Khadiga O. H. Elhag, Siddig E. Y. Abdallah, Hamdan M. Hamdan, Mona O.A. Awadelkarim, Myada F. O. Ali, Sara I. A. Latif, and Elwaleed M. Elamin
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.