Definitions and Diagnosis
Fever was defined as an axillary temperature of 37.3°C or above.
Secondary bacterial infection was diagnosed based on signs and symptoms
of bacteremia or pneumonia with identification of a new bacterial
pathogen in endotracheal aspirate or lower respiratory tract sputum
culture. For patients diagnosed as having ventilator-associated or
hospital-acquired pneumonia, treatment was planned according to
available guidelines. Acute respiratory distress was diagnosed and
graded according to the Berlin 2015 diagnostic criteria. Patients with
daily cardiac-specific troponin levels above normal range underwent
echocardiographic evaluation for emerging cardiac pathologies.
Coagulopathy was defined as prothrombin time 3 s longer than normal and
activated partial thromboplastin time 5 s longer than normal. Treatment
strategy was determined based on disease severity in accordance with the
COVID-19 adult diagnosis and treatment guidelines issued by the Turkish
Ministry of Health. Macrophage activation syndrome was presumed in
patients who despite treatment exhibited findings such as refractory
fever, persistently high or increasing CRP and ferritin levels, elevated
D-dimer level, lymphopenia or thrombocytopenia, abnormal liver function
indicators, hypofibrinogenemia, or elevated triglyceride levels. If
daily follow-up of these parameters showed continued deterioration that
could not be explained by secondary bacterial infection, 400 mg
tocilizumab for macrophage activation syndrome was administered if not
contraindicated. Another dose of 400 mg tocilizumab was administered if
no significant improvement in laboratory parameters and vital signs was
observed after 24 hours.