Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID-19 patients with pre-existing co-morbidities

Background: The difficulty to predict fatal outcomes in COVID-19 patients, impacts in the general morbidity and mortality due to SARSCoV2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre-existing co-morbidities. Methods. A cohort of one hundred and forty-seven patients hospitalized for severe COVID19 was included in a descriptive, observational, single-center, and prospective study. Patients were recruited during the first COVID-19 pandemic wave (April-Nov, 2020). Data were collected from the clinical history while immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leukocytes. Patients were grouped according to the outcome in survivor or decease. The prognostic value of leukocytes, cytokines or HLA-DR, CD39, and CD73 was calculated. Results: Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the decease group. Mixed hypercitokinemia, including inflammatory(IL-6) and anti-inflammatory(IL-10) cytokines, was more evident in deceased patients. In the decease group, lymphopenia with a higher NLR value was present. HLA-DR expression and the percentage of CD39+ cells were higher than non COVID-19 patients, but remain similar despite outcome. ROC analysis and cut-off value of NLR (69.6%, 9.4), pNLR (71.1%, 13.6), IL-6 (79.7%, 135.2 pg/mL). Conclusion: The expression of HLA-DR, CD39, and CD73, as many serum cytokines (other than IL-6) and chemokines levels do not show prognostic potential compared to NLR and pNLR values. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project was supported by the Mexican National Research Council (CONACyT), Project No. 313494 (awarded to CLM). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Our study was approved by the Ethic committee in the Centro Medico Nacional Siglo XXI. Instituto Mexicano del Seguro Social (IMSS). Ciudad de Mexico, Mexico. (Approved number:R-2020-785-095). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors