A 48-year-old South Asian woman (Patient A) from Bangladesh (height 168 cm, weight 80 kg) was admitted to the medical ward for three days after which she was transferred to the ICU; she had cough and increasing dyspnea for three days before hospital admission. Comorbidities included hypertension, hypercholesterinemia, coronary artery disease, previous stroke (fully recovered), and type 2 diabetes. On admission, her laboratory results were as follows: hemoglobin (Hb): 143 g/L, white blood cells (WBC): 9.0 × 10⁹/L, lymphocytes: 1.4 × 10⁹/L, platelets: 261 × 10⁹/L, international normalized ratio (INR): 1.1, D-dimer: 510 μg/L, fibrinogen plasma concentration: 8.4 g/L, and C-reactive protein (CRP): 52 mg/L. Her chest radiograph showed cardiomegaly and extensive bilateral peripherally predominant ground-glass opacities. Polymerase chain reaction (PCR) result was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and negative for influence/respiratory syncytial virus (RSV). Blood cultures were negative. The patient was treated with nasal oxygen therapy and antibiotics (ceftriaxone and doxycycline, according the hospital’s COVID-19 protocol). Antiviral therapy and dexamethasone were not administered. Later, CRP increased to 137 mg/L on the second day of hospitalization. The patient was transferred to the ICU on the third day because of increased respiratory rate and oxygen requirement. ROTEM performed 2 hours after ICU admission (Fig. 1A) revealed that Patient A was hypercoagulable with the EXTEM assay showing an increased clot firmness with an amplitude of clot firmness 5 minutes after coagulation time (CT) (A5) of 65 mm and a maximum clot firmness (MCF) of 78 mm, indicating hypercoagulability with a high risk of thrombosis [4]. FIBTEM also showed increased clot firmness (A5 41 mm and MCF 50 mm), indicating increased fibrinogen concentration and fibrin polymerization. Furthermore, the EXTEM lysis index 60 minutes after CT (LI60) was 97%, i.e., in the physiologic range (82–97.9%), whereas FIBTEM LI60 was 100% [5]. Treatment consisted of continuation of antibiotics, enoxaparin 40 mg twice a day in view of ROTEM results, and high flow nasal oxygen and intermittent face mask continuous positive airway pressure (CPAP) therapies. The patient did not need intermittent positive pressure ventilation (IPPV) or any vasoactive support. Laboratory results on the second day in the ICU were as follows: Hb: 131 g/L, WBC: 10.8 × 10⁹/L, platelet count: 307 × 10⁹/L, INR: 1.1, activated partial thromboplastin time (APTT) ratio: 1.3, D-dimer: 510 μg/L, and CRP: 196 mg/L. The patient recovered well and was transferred from the ICU to the medical ward after two days in the ICU with a CRP of 73 mg/L and was discharged three days later with a prescription of her usual medication plus enoxaparin 40 mg once daily for 2 weeks. The patient did not show any clinical signs of thrombosis during her hospital stay.

A 68-year-old Caucasian man (Patient B) from the United Kingdom (height 177 cm, weight 85 kg) was admitted with cough and a week-long increasing dyspnea, before which he was healthy. His wife and daughter probably had COVID-19 with resolving symptoms, and they were all living in the same house. The patient markedly experienced shortness of breath on the day of admission to the emergency department (ED) and, therefore, called an ambulance. His laboratory results on admission were as follows: Hb: 140 g/L, creatinine: 117 μmol/L, WBC: 8.6 × 10⁹/L, lymphocytes: 0.2 × 10⁹/L, platelet count: 126 × 10⁹/L, INR: 1.4, APTT ratio: 1.3, D-dimer > 20,000 μg/L (i.e., higher than the upper limit of the measurement range), fibrinogen plasma concentration: 6.8 g/L, and CRP: 336 mg/L. His chest radiograph showed dense bilateral mid-zone and right lower zone consolidation. PCR result was positive for SARS-CoV-2 and negative for influenza/RSV. Blood cultures showed coagulase-negative staphylococci. The patient was treated with antibiotics (ceftriaxone and doxycycline, according the hospital’s COVID-19 protocol). Antiviral therapy and dexamethasone were not administered. As the patient was severely hypoxemic in the ED, he was transferred directly to the ICU. Orotracheal intubation and IPPV (positive end-expiratory pressure 15 mmHg) were performed about 3 hours after ICU admission as respiratory effort was not improved by face mask CPAP therapy. Chest radiography repeated after intubation showed bilateral interstitial lung changes similar to the imaging conducted earlier on the same day. Prone position did not improve oxygenation. Laboratory results on the next day were as follows: Hb: 133 g/L, creatinine: 265 μmol/L, WBC: 16.3 × 10⁹/L, platelet count: 56 × 10⁹/L, INR: 1.6, APTT ratio: 1.5, D-dimer: 4,340 μg/L, fibrinogen plasma concentration: 2.9 g/L, and CRP: 478 mg/L. By ROTEM, Patient B presented with hypocoagulability in the EXTEM assay with a prolonged CT of 99 s, clot formation time (CFT) of 253 s, and decreased clot firmness amplitudes (A5, 22 mm and MCF, 48 mm) (Fig. 1B). Furthermore, EXTEM and FIBTEM analyses demonstrated a complete fibrinolysis shutdown [5]. Both hypocoagulability and fibrinolysis shutdown have been shown to be associated with increased mortality in bacterial sepsis [3,6]. The FIBTEM trace was within normal limits which may be owing to impaired fibrin polymerization, given that fibrinogen concentration was elevated. The patient deteriorated within a few hours of ICU admission and died the following day despite invasive ventilation, norepinephrine for hypotension, and renal replacement therapy for acute kidney failure. Patient B did not show any clinical signs of thrombosis during his hospital stay.