Reference Method Case Definitions
Patients were categorized as having a final diagnosis of Bacterial
Infection33,34, COVID-19 Viral
Infection30,31, Non-COVID-19 Viral
Infection33,34 and Non-Infectious
conditions33,34 were based on the following Case
Definitions (Figure 1). The Case Definition for COVID-19 Viral Infection
was a composite of (i) clinical findings (e.g. fever ≥37.8°C and at
least one of the following respiratory symptoms, which must be of acute
onset: persistent cough (with or without sputum), hoarseness, nasal
discharge or congestion, shortness of breath, sore throat, wheezing,
sneezing), inpatients with new respiratory symptoms or fever without
another cause or worsening of a pre-existing respiratory condition
cough, shortness of breath, or difficulty breathing and; (ii)
epidemiological evidence of recent exposure to COVID-19 and; (iii)
either positive SARS-CoV-2 rRT-PCR or a combination of radiological
changes consistent with COVID 19 along with lymphocytopenia and lack of
an alternative diagnosis. Due to a lack of a gold standard for COVID-19
diagnosis, the Case Definition for COVID-19 Viral infection was informed
by guidance from both the European Centre for Disease Prevention and
Control (ECDC) and the U.S. Centers for Disease Control and Prevention
(CDC).30,31 Patients were considered to have a final
diagnosis (i.e. Case Definition) of Bacterial LRTI/Pneumonia if found to
have negative molecular viral testing (SARS-CoV-2, RSV, Influenza) and
one of the following: 1) chest imaging with new onset focal
consolidation and CRP ≥100 mg/L34 and PCT
≥0.25ng/mL33 (bacterial pneumonia)] or 2) No
consolidation on chest imaging and CRP ≥4034 mg/L and
PCT ≥0.1ng/mL33 (bacterial LRTI) with or without
positive bacterial culture. The Case Definition for a Non-COVID-19 Viral
Infection was defined as the absence of bacterial pathogen or positive
rRT-PCR detection of a non-COVID-19 viral respiratory pathogen and
laboratory findings consistent with viral infection such as
lymphocytosis, PCT <0.1ng/mL33, CRP
<40 mg/L34; The Case Definition for a
Non-Infectious condition was defined as having clear evidence of
alternative diagnosis with absence of a detected pathogen, chest imaging
that was negative for consolidation/infiltrates consistent with
infection, Procalcitonin <0.1 ng/mL.33 The
final diagnosis, based on the Case Definitions described above, was
confirmed by an independent physician.