key: cord-0964445-hwo8kc8e
authors: Li, Yichen; Jiao, Na; Zhu, Lixin; Cheng, Sijing; Zhu, Ruixin; Lan, Ping
title: Non-febrile COVID-19 patients were common and often became critically ill: a retrospective multicenter cohort study
date: 2020-06-08
journal: Crit Care
DOI: 10.1186/s13054-020-03037-8
sha: 2061c8aac28fb5d1f3af2959b3015ef44f88e03f
doc_id: 964445
cord_uid: hwo8kc8e

nan

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. Fever promotes inflammatory reaction, which may help control viral infection leading to beneficial outcomes. However, fever-induced upregulation of the inflammatory cytokines such as IL-1, TNF, and IL-6 may contribute to cytokine storm that contributes to critical illness. These double-edged effects of fever may explain the absence of correlation between fever and the disease outcome.

Given the high proportion of non-febrile patients in COVID-19, and that 20% non-febrile patients became critically ill, heightened attention for this elusive group of patients may be required for a better containment of the pandemic. Our finding is a timely alarm for health care workers and general population that temperature monitoring alone does not identify many of the COVID-19 patients.

Abbreviations ARDS: Acute respiratory distress syndrome; COVID-19: Coronavirus disease 2019; FiO 2 : Fraction of inspired oxygen; SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus-2

Clinical characteristics of COVID-19 in New York City

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Local action of the proinflammatory cytokines IL-1beta and IL-6 on intracranial meningeal nociceptors

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Authors' contributions LZ, RL, and PL conceived and designed this study. YL, NJ, SC, and LZ collected the data. All authors analyzed the data. YL, NJ, and LZ prepared the manuscript. All authors critically revised the manuscript and approved the final version.

This study was partially supported by the National Natural Science 

The data that support the findings of this study are available from the corresponding author upon reasonable request.Ethics approval and consent to participate Our study was approved by the institutional review boards of the Sun Yatsen University and the participating hospitals. The informed consent was waived because this chart review did not involve any patient tissue or interview.

Not applicable.

All authors declare no competing interests.Received: 20 May 2020 Accepted: 27 May 2020