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Abstract The aim of this study was to characterize the systemic cytokine signature of critically ill COVID-19 patients in a high mortality setting aiming to identify biomarkers of severity, and to explore their associations with viral loads and clinical characteristics. We studied two COVID-19 critically ill patient cohorts from a referral centre located in Central Europe. The cohorts were recruited during the pre-alpha/alpha (November 2020 to April 2021) and delta (end of 2021) period respectively. We determined both the serum and bronchoalveolar SARS-CoV-2 viral load and identified the variant of concern (VoC) involved. Using a cytokine multiplex assay, we quantified systemic cytokine concentrations and analyzed their relationship with clinical findings, routine laboratory workup and pulmonary function data obtained during the ICU stay. Patients who did not survive had a significantly higher systemic and pulmonary viral load. Patients infected with the pre-alpha VoC showed a significantly lower viral load in comparison to those infected with the alpha- and delta-variants. Levels of systemic CTACK, M-CSF and IL-18 were significantly higher in non-survivors in comparison to survivors. CTACK correlated directly with APACHE II scores. We observed differences in lung compliance and the association between cytokine levels and pulmonary function, dependent on the VoC identified. An intra-cytokine analysis revealed a loss of correlation in the non-survival group in comparison to survivors in both cohorts. Critically ill COVID-19 patients exhibited a distinct systemic cytokine profile based on their survival outcomes. CTACK, M-CSF and IL-18 were identified as mortality-associated analytes independently of the VoC involved. The Intra-cytokine correlation analysis suggested the potential role of a dysregulated systemic network of inflammatory mediators in severe COVID-19 mortality.

Background and Objectives: The COVID-19 disease has significantly burdened the healthcare system, including all units of severe patient treatment. Non-intensive care units were established to rationalize the capacity within the Intensive Care Unit (ICU) and to create a unit where patients with Acute Respiratory Distress Syndrome (ARDS) could be treated with non-invasive Continuous Positive Air Pressure (CPAP) outside the ICU. This unicentric retrospective study aimed to assess the efficacy of NIV Treatment in Patients of the fourth pandemic wave and how its application affects the frequency and mortality of ICU-treated patients at University Hospital Rijeka compared to earlier waves of the COVID-19 pandemic. Furthermore, the study showcases the effect of the Patient/Nurse ratio (P/N ratio) on overall mortality in the ICU. Materials and Methods: The study was conducted on two groups of patients with respiratory insufficiency in the second and third pandemic waves, treated in the COVID Respiratory Centre (CRC) (153 patients). We also reviewed a cohort of patients from the fourth pandemic wave who were initially hospitalized in a COVID-6 non-intensive unit from 1 October 2021 to 1 November 2022 (102 patients), and some of them escalated to CRC. Results: The introduction of the CPAP non-invasive ventilation method as a means of hypoxic respiratory failure treatment in non-intensive care units has decreased the strain, overall number of admissions, and CRC patient mortality. The overall fourth wave mortality was 29.4%, compared to the 58.2% overall mortality of the second and third waves. Conclusions: As a result, this has decreased CRC patient admissions and, by itself, overall mortality.

Studies assessing the dynamics and duration of antibody responses following SARS-CoV-2 infection or vaccination are an invaluable tool for vaccination schedule planning, assessment of risk groups and management of pandemics. In this study, we developed and employed ELISA assays to analyze the humoral responses to Nucleocapsid and Spike proteins in vaccinated health-care workers (HCW) and critically ill COVID-19 patients. Sera of more than 1000 HCWs and critically ill patients from the Clinical Hospital Center Rijeka were tested across a one-year period, encompassing the spread of major SARS-CoV-2 variants of concern (VOCs). We observed 97% of seroconversion in HCW cohort as well as sustained anti-Spike antibody response in vaccinees for more than 6 months. In contrast, the infection-induced anti-Nucleocapsid response was waning significantly in a six-month period. Furthermore, a substantial decrease in vaccinees’ anti-Spike antibodies binding to Spike protein of Omicron VOC was also observed. Critically ill COVID-19 patients had higher levels of anti-Spike and anti-Nucleocapsid antibodies compared to HCWs. No significant differences in anti-Spike and anti-Nucleocapsid antibody levels between the critically ill COVID-19 patients that were on non-invasive oxygen supplementation and those on invasive ventilation support were observed. However, stronger anti-Spike, but not anti-Nucleocapsid, antibody response correlated with a better disease outcome in the cohort of patients on invasive ventilation support. Altogether, our results contribute to the growing pool of data on humoral responses to SARS-CoV-2 infection and vaccination.

While SARS-CoV-2 detection in sputum and swabs from the upper respiratory tract has been used as a diagnostic tool, virus quantification showed poor correlation to disease outcome and thus, poor prognostic value. Although the pulmonary compartment represents a relevant site for viral load analysis, limited data exploring the lower respiratory tract is available, and its association to clinical outcomes is relatively unknown. Using bronchoalveolar lavage (BAL) and serum samples, we quantified SARS-CoV-2 copy numbers in the pulmonary and systemic compartments of critically ill patients admitted to the intensive care unit of a COVID-19 referral hospital in Croatia during the second and third pandemic waves. Clinical data, including 30-day survival after ICU admission, were included. We found that elevated SARS-CoV-2 copy numbers in both BAL and serum samples were associated with fatal outcomes. Remarkably, the highest and earliest viral loads after initiation of mechanical ventilation support were increased in the non-survival group. Our results imply that viral loads in the lungs contribute to COVID-19 disease severity, while blood titers correlate with lung virus titers, albeit at a lower level. Moreover, they suggest that BAL SARS-CoV-2 copy number quantification at ICU admission may provide a predictive parameter of clinical COVID-19 outcomes.