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To the Editor: Recent cohort studies frequently reported low rate of fever in coronavirus disease 2019 (COVID-19) patients [1, 2], which was in sharp contrast with previous studies that reported > 98% of patients presented fever on admission [3, 4]. Fever is a protective response for infections and an important criterion in the diagnosis of COVID-19. To understand the prevalence of fever in COVID-19 and its correlation with other symptoms and outcomes, we conducted a chart review of 252 hospitalized patients from 15 participating hospitals in Guangdong, Hubei, and Jiangxi provinces, China, from January 19 to March 6, 2020 (Table 1). Diagnosis of COVID-19 was based on positive severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) reverse transcription-PCR test. Our study was approved by the institutional review boards of the Sun Yat-sen University and the participating hospitals. Demographic, clinical, laboratory, treatment, and outcome data were collected. The hospital course was reviewed for severity of disease. Critically ill patients were defined as those admitted to the ICU requiring mechanical ventilation or had a fraction of inspired oxygen (FiO2) of at least 60% [5]. SPSS (Statistical Package for the Social Sciences) version 24.0 software (SPSS Inc.) was used for Mann-Whitney U, chi-square, and the Fisher’s exact test. All statistical tests were two sided, with p values of < 0.05 considered to be statistically significant. We found that, on admission, 197 (78%) patients had temperatures ≥ 37.3 °C, 93 (37%) patients had temperatures > 38 °C, and 13 (5%) patients had temperatures > 39 °C (Table 1). We then examined the differential symptoms and outcomes between febrile (≥ 37.3 °C) and non-febrile (< 37.3 °C) patients. The most common symptoms on admission in both febrile and non-febrile patients were cough, poor appetite, and sputum production (Table 1). Smaller proportion of the non-febrile patients presented cough, poor appetite, and sputum production, compared to the febrile patients. In contrast, larger proportion of the nonfebrile patients presented cephalalgia. The negative correlation between cephalalgia and fever is intriguing. Currently, there is no evidence for SARS-CoV-2 infection in brain tissue, although ACE2 expression in neuron was observed. Perhaps inflammatory cytokines from peripheral blood caused headache [6] in COVID-19. Cephalalgia may be a useful sign for the identification of nonfebrile COVID-19, when epidemiological evidence for the infection exists. No significant difference in any of the recorded comorbidities was observed between febrile and nonfebrile patients. Similar high proportions of febrile (157 [80%]) and non-febrile patients (43 [78%]) required oxygen supplementation (Table 1), indicating that respiratory system was the most affected system for both groups of patients.

Non-febrile COVID-19 patients were common and often became critically ill: a retrospective multicenter cohort study