Fever Patterns, Cytokine Profiles and Outcomes in Covid-19

Ng, Deborah H L; Choy, Chiaw Yee; Chan, Yi-Hao; Young, Barnaby E; Fong, Siew-Wai; Ng, Lisa F P; Renia, Laurent; Lye, David C; Chia, Po Ying

BACKGROUND: Prolonged fever is associated with adverse outcomes in dengue viral infection. Similar fever patterns are observed in COVID-19 with unclear significance. METHODS: We conducted a hospital-based case-control study of patients admitted for COVID-19 with prolonged fever (fever>7 days) and saddleback fever (recurrence of fever, lasting less than 24 hours, after defervescence beyond day 7 of illness). Fever was defined as a temperature of ≥60.0oC. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation and mortality. RESULTS: A total of 142 patients were included in the study. 12.7% (18/142) of cases had prolonged fever and 9.9% (14/142) had saddleback fever. Those with prolonged fever had a median duration of fever for 10 days (IQR 9–11 days) for prolonged fever cases, while fever recurred at a median of 10 days (IQR 8–12 days) for those with saddleback fever. Both prolonged (27.8% vs 0.9%, p <0.01) and saddleback fever (14.3% vs 0.9%, p= 0.03) were associated with hypoxia compared to controls. Cases with prolonged fever were also more likely to require ICU admission compared to controls (11.1% vs 0.9%) (p=0.05). Patients with prolonged fever had higher IP-10 and lower IL-1α levels compared to those with saddleback fever at the early acute phase of disease. CONCLUSION: Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Patients with saddleback fever appeared to have good outcomes regardless of the fever.