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.