COVID-19 disease—Temporal analyses of complete blood count parameters over course of illness, and relationship to patient demographics and management outcomes in survivors and non-survivors: A longitudinal descriptive cohort study
Authors: Lanini Simone , Montaldo Chiara , Nicastri Emanuele , Vairo Francesco , Agrati Chiara , Petrosillo Nicola , Scognamiglio Paola , Antinori Andrea , Puro Vincenzo , Di Caro Antonino , De Carli Gabriella , Navarra Assunta , Agresta Alessandro , Cimaglia Claudia , Palmieri Fabrizio , D’Offizi Gianpiero , Marchioni Luisa , Kobinger Gary Pignac , Maeurer Markus , Girardi Enrico , Capobianchi Maria Rosaria , Zumla Alimuddin , Locatelli Franco , Ippolito Giuseppe 
Published: December 2020

Background
Detailed temporal analyses of complete (full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease, could identify prognostic clinical biomarkers.

Methods
From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. 9 CBC parameters were studied as continuous variables [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribution width (RDW %)]. Model-based punctual estimates, as average of all patients’ values, and differences between survivors and non-survivors, overall, and by co-morbidities, at specific times after symptoms, with relative 95% CI and P-values, were obtained by marginal prediction and ANOVA- style joint tests. All analyses were carried out by STATA 15 statistical package.

Main findings
379 COVID-19 patients [273 (72% were male; mean age was 61.67 (SD 15.60)] were enrolled and 1,805 measures per parameter were analysed. Neutrophils’ counts were on average significantly higher in non-survivors than in survivors (P<0.001) and lymphocytes were on average higher in survivors (P<0.001). These differences were time dependent. Average platelets’ counts (P<0.001) and median platelets’ volume (P<0.001) were significantly different in survivors and non-survivors. The differences were time dependent and consistent with acute inflammation followed either by recovery or by death. Anaemia with anisocytosis was observed in the later phase of COVID-19 disease in non-survivors only. Mortality was significantly higher in patients with diabetes (OR = 3.28; 95%CI 1.51–7.13; p = 0.005), obesity (OR = 3.89; 95%CI 1.51–10.04; p = 0.010), chronic renal failure (OR = 9.23; 95%CI 3.49–24.36; p = 0.001), COPD (OR = 2.47; 95% IC 1.13–5.43; p = 0.033), cardiovascular diseases (OR = 4.46; 95%CI 2.25–8.86; p = 0.001), and those >60 years (OR = 4.21; 95%CI 1.82–9.77; p = 0.001). Age (OR = 2.59; 95%CI 1.04–6.45; p = 0.042), obesity (OR = 5.13; 95%CI 1.81–14.50; p = 0.002), renal chronic failure (OR = 5.20; 95%CI 1.80–14.97; p = 0.002) and cardiovascular diseases (OR 2.79; 95%CI 1.29–6.03; p = 0.009) were independently associated with poor clinical outcome at 30 days after symptoms’ onset.

Interpretation
Increased neutrophil counts, reduced lymphocyte counts, increased median platelet volume and anaemia with anisocytosis, are poor prognostic indicators for COVID19, after adjusting for the confounding effect of obesity, chronic renal failure, COPD, cardiovascular diseases and age >60 years.