Grading of Lymphopenia and Neutropenia and Definition of Infections

Lymphopenia was defined as ALC values (remove absolute lymphocyte counts) below the lower limit of normal (LLN = 1,000 lymphocytes/μl). We followed the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 to classify grading of lymphopenia and neutropenia. Specifically, ALC values higher than 1,000 lymphocytes/μl are considered non lymphopenic (Grade 0); ALC values of 1,000–800 lymphocytes/μl are scored as Grade 1 lymphopenia; ALC values of 500–800 lymphocytes/μl are scored as Grade 2 lymphopenia; ALC values of 200–500 lymphocytes/μl are scored as Grade 3 lymphopenia; and ALC values of <200 lymphocytes/μl are scored as Grade 4 lymphopenia. Any ALC value less or equal to 500 lymphocytes/μl is called severe lymphopenia in the manuscript. Similarly, neutropenia is any ANC value less than or equal to 1,500 neutrophils/μl while severe neutropenia any ANC value less than or equal to 500 neutrophils/μl.

Infectious diseases are classified based on the World Health Organization’s International Statistical Classification of Diseases–10th Revision (ICD-10). Infections were divided in non-serious infections or serious infections, with the latter requiring hospitalization.

Serious infections belong to four categories: pneumonia, sepsis, urinary tract infections, and other. Pneumonia are defined by clinical features, radiological findings, as well as positive sputum cultures, polymerase chain reaction (PCR) testing, or serum antigens (9). Patients with pneumonia could have a positive viral culture (e.g. Influenza A/B) but also have a defined consolidation by imaging. Culture positive infections are serious infections with an associated causative agent. This agent is either bacterial, viral, or fungal and is identified by positive microbial culture, PCR, or antigen detection (e.g. Streptococcus pneumoniae antigen, Fungitell β-D Glucan assay). Sites of positive cultures are blood (e.g. Streptococcus pneumoniae antigen, Escherichia coli blood culture), upper or lower respiratory tract secretions, or urine.

Non-serious infections are categorized into upper respiratory tract infections, urinary tract infections, diarrhea disease, and skin infections. Non-infectious related hospital stays are the number of hospital admissions due to other causes than infections.