## 2 Materials and Methods  
### Subjects  
Altogether, 53 patients with PCR-confirmed SARS-CoV-2 were included in the study. Patients were admitted to the Clinic of Pneumology and Phthisiology, Martin University Hospital, Slovakia, due to chest X-ray/CT signs of bilateral pneumonia and acute hyposemic respiratory failure requiring oxygen supplementation (oxygen saturation at <94% in room air). In general, patients presented with typical symptoms of COVID-19: fever, cough, dyspnoea, weakness, fatigue, nylalgia and arthralgia, loss of smell and taste, and loss of appetite. Some patients suffered from gastrointestinal symptoms (diarrhoea) as well. Laboratory results on admission showed increased inflammatory markers (CRP, IL-6, ferritin, fibrinogen) and hypoxemic respiratory failure, and changes in differential blood count included leuccytosis, lymphopenia, neutrophil, and eosinophilsemia in most patients.  
During the study, patients received either standard hospital enteral nutrition or a diabetic diet (patients with diabetes). Patients incapable of oral food intake received the equivalent for enteral nutrition via nasogastric tube. None of the included patients had percutaneous endoscopic gastrostomy/jejunostomy. Neither nutritional supplementation nor parenteral nutrition was administered. When necessary, but only sporadically, patients received crystalloid solutions to treat dehydration or mineral imbalance.  
Oxygen was administered via nasal cannula, face mask, or face mask with a rebreathing bag with flow adjusted to achieve target oxygen saturation of 94%. Seven patients required high-flow nasal oxygen therapy (HFNO), and in case of hypoxemic-hypercapnic respiratory failure, three received non-invasive ventilation (NIV). In patients with severe and critical clinical condition requiring a very high flow of oxygen, saturation of 90% was considered sufficient. None of the included patients received mechanical ventilation during sample collection; however, two patients were later intubated and mechanically ventilated. Apart from oxygen supply, patients were treated with dexamethasone (all patients, dose of 6 mg/day for a duration of 10 days); antivirals (remdesivir or favipiravir if eligible according to local guidelines--duration of symptoms less than 7 days), n = 17; antibiotics (in case of bacterial superfinfection or its suspicion), n = 53; LMWH, n = 49; vitamins: vitamin C, n = 17, vitamin D, n = 19; zinc, n = 14; and betaglucans, n = 44.  
Patients were divided into two subgroups: Group A (n = 34) contained patients with a positive outcome (survivors), while Group B (n = 19) contained patients with a negative outcome, i.e., patients with a worsening condition during the sampling period, or those who died (10 were dead at the time of manuscript preparation). All known patient comorbidities at the time of study enrolment are listed in Table 1. To assess the patients' condition, the determining criterion was the need for increasing/decreasing oxygen flow or switch to HFNO, NIV, or mechanical ventilation to achieve target oxygen saturation, together with clinical evaluation and known clinical outcome. Due to various causes such as hospital discharge before Day 7, death, or even patient disagreement with other blood collections, the number of samples on Day 3 or Day 7 is slightly reduced. All details about subjects included in the study are summarised in Table 1.  
As controls, plasma samples from age- and gender-matched subjects without any acute or chronic inflammatory diseases, any type of respiratory failure, or any pulmonary diseases, regardless of common highly age-related conditions (hypertensia, obesity, and others in the representative sample of the population) were used, representing a'sample of the normal population', collected in a fasting state without any additional criteria. Included were 55 subjects: median age 64, IQR 18, female n = 25.