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.