Comparative Analysis of Clinical and Paraclinical Manifestations of Neonatal COVID-19 and Sepsis: A Study from Shiraz, Iran

Background: Neonates are particularly vulnerable to COVID-19, presenting with symptoms that may overlap with those seen in neonatal sepsis. Objectives: This study aims to compare the clinical and paraclinical manifestations of COVID-19 and sepsis in neonates. Methods: A cohort of 48 neonates diagnosed with either sepsis or COVID-19 between February 2020 and December 2020 at Namazi and Hafez hospitals in Shiraz, Iran, were included in this analysis. Clinical and paraclinical parameters were systematically recorded and analyzed. Results: Among the observed parameters, poor feeding (54.16% vs. 20.83%) and lethargy (33.33% vs. 8.33%) were significantly more prevalent in neonates with sepsis compared to those with COVID-19 (P = 0.01, 0.03). Blood cultures were positive in 100% of the sepsis group, while only 8.3% of COVID-19 cases showed positive blood cultures (P < 0.001). All urine cultures in COVID-19 cases were sterile, whereas 16.6% of neonates with sepsis had positive urine cultures (P = 0.29). Platelet counts were significantly lower in the sepsis group compared to COVID-19 group (199.08 ± 184.61 × 10³/mm³ vs. 296.73 ± 160.15 × 10³/mm³) (P = 0.03) and C-reactive protein (CRP) levels were notably higher in sepsis cases (96.83 ± 53.55 mg/dL vs. 29.14 ± 52.72 mg/dL) (P < 0.001). Radiological findings showed no significant differences between the groups. Neonatal mortality was higher in the COVID-19 group compared to the sepsis group (25% vs. 4.2%) (P = 0.35). Conclusions: This study reveals distinct clinical and paraclinical differences between neonatal COVID-19 and sepsis. Poor feeding and lethargy are more common in sepsis, and neonates with sepsis exhibit higher rates of positive cultures and worse hematologic parameters compared to those with COVID-19. These findings underscore the need for early differential diagnosis and tailored management strategies in neonatal infectious diseases.