Discussion
To our knowledge, this is among the systematic review and meta-analysis
of China-based studies comparing the clinical symptoms between patients
with severe vs. non-severe form of COVID-19 pneumonia. We observed no
gender difference, which is consistent with the latest report11,13,16,17. Although fever and cough are relatively
common symptoms, we found the incidences of fever, dyspnea and diarrhea
are all significantly higher in patients with severe COVID-19 pneumonia,
suggesting they could be alarming symptoms that worth extra medical
attention. Although our findings in dyspnea were similar to previous
reports 10,11, we have to point out that certain
discrepancy exists: for example, some reported no difference in the
incidence of fever and diarrhea 10,11,13, or even
dyspnea 13. One possible explanation is that in those
reports, the sample size was relatively small and studies were reported
at relatively early phase of this pandemic COVID-19 pneumonia.
The early symptoms/signs of COVID-19 pneumonia can be indistinguishable
from those of other common respiratory infectious diseases, and could
exhibit certain similarities to those of severe acute respiratory
syndrome associated coronavirus (SARS-CoV) and middle East respiratory
syndrome coronavirus (MERS-CoV) infections 29,30.
However, patients with COVID-19 rarely had obvious signs and symptoms of
upper respiratory tract (e.g. nasal obstruction, rhinorrhea, runny nose,
sore throat). In addition, intestinal signs and symptoms such as
diarrhea were less common in COVID-19 pneumonia patients (below 10%
even in severe form), while about 20-25% of patients with MERS-CoV or
SARS-CoV infection presented with diarrhea 30. It
should be noted however that fever in COVID-19 pneumonia patients
(10.8%) was more common than SARS-CoV (1%) and MERS-CoV (2%)31.
As COVID-19 pneumonia can have a full spectrum of clinical
presentations, it is therefore crucially important to recognize alarming
symptoms that signal progression to severe form 14, as
such information will not only help us better triage our patients, but
also wisely use our medical resources which are often in shortage during
pandemic crisis. This study has clearly shown that fever, dyspnea and
diarrhea could be such alarming symptoms that warrant timely medical
attention. Meanwhile, as can be seen from our validation results, fever
and dyspnea are more common in patients with severe COVID-19 pneumonia.
However, there was no statistically significant difference between the
two groups in gastrointestinal symptoms such as nausea, diarrhea or
abdominal pain (p >0.05). However certain limitation exists
in this study: 1) since most data are from retrospective studies and
case reports, which intend to report successful management, selection
bias could exist. However, considering some studies reported that most
patients were still hospitalized at the time of publication (for
example, 93.6% (1029/1099) in Article 1 and 61.6% (85/138) inArticle 2 , Fig. 2 ), the selection bias could have little
impact; 2) the data collection in some cases is not complete, especially
for rare symptoms such as hemoptysis and conjunctivitis, hence the
statistical power should be carefully interpreted for those symptoms; 3)
from data analysis perspective using published studies, although
symmetry was observed, it is challenging to evaluate publication bias
due to limited number of studies included. However, since COVID-19 is
new disease entity, both positive and negative results will likely have
the chance to be published, which should theoretically reduce the
publication bias for future secondary analysis.