Severe COVID-19 and routine biomarker patterns

In acute infectious diseases, the composition of the blood changes. That includes proteins, blood cells and smaller solutes. Routine blood tests have a fundamental role in the diagnosis and follow-up of patients with severe infections. Similar to other severe infections, high levels of inflammatory markers are seen during the acute phase of a SARS-CoV-2 or COVID-19 infection. What distinguished COVID-19 in year 2020 from other viral diseases, was the high pathogenicity increasing the likelihood of affecting other common biomarkers.

The aim of this thesis was to investigate the prognostic importance of dynamics and trends of routine electrolyte, coagulation and kidney biomarkers in patients with severe COVID-19 at Karolinska University Hospital during the first phase of the pandemic in Sweden.

Study I: A retrospective cohort study of 429 patients. In this study we investigated how trends of platelet counts and D-dimer levels were associated with mortality, thrombosis and difference in anticoagulant treatment routine. We found that increasing platelet levels and decreasing D-dimer levels, during the first week of hospitalization, were associated with improved survival and reduced thrombotic risk and enhanced prophylaxis with LMWH coincided with improved outcomes.

Study II: In this retrospective cohort study of 406 patients, we evaluated presence and importance of electrolyte and acid-base imbalance. Hyponatremia was seen in many patients at admittance and was found to be associated with future need of mechanical ventilation. However, development of hypernatremia was common, occurring in 42% of the patients in the cohort, and was associated with increased hospital stay and death.

Study III: A retrospective study of 45 patients with COVID-19, undergoing brain magnetic resonance imaging (MRI), which were assessed for the presence/absence of a normal posterior pituitary gland (bright spot). Hypernatremia and polyuria consistent with central diabetes insipidus (DI) were observed in 14 patients (31%), whereof 6 (13%) had a full laboratory workup and fulfilled the diagnostic criteria of DI; all 14 patients with suspected DI lacked the bright spot, suggesting a vasopressin-depleted state.

Study IV: In the last study, designed as a retrospective cohort study of 286 patients, we studied acute kidney injury (AKI) and related biomarkers in severe COVID-19. AKI developed in 38% of the patients and a higher mortality was seen in the group with AKI. Discrepant results between eGFR creatinine (eGFRCR) and eGFR Cystatin C (eGFRCYS) was common, especially in the ICU patients, and the development of a pronounced discrepancy was related to poor outcome.

To conclude, during hospitalization for severe COVID-19 the biomarker pattern fluctuates depending on improvement or worsening of the disease. In this thesis we describe the changes in some of our common blood tests and how they associate with outcome. Therefore, an evaluation of the dynamics of the biomarkers is an important part in the assessment of disease development, treatment and prognosis.

List of scientific papers

I. Sjöström A, Wersäll JD, Warnqvist A, Farm M, Magnusson M, Oldner A, Ågren A, Antovic J, Bruzelius M. Platelet Count Rose While D-Dimer Levels Dropped as Deaths and Thrombosis Declined- An Observational Study on Anticoagulation Shift in COVID-19. Thromb Haemost. 2021 Dec;121(12):1610-1621.
https://doi.org/10.1055/a-1477-3829

II. Sjöström A, Rysz S, Sjöström H, Höybye C. Electrolyte and acid-base imbalance in severe COVID-19. Endocr Connect. 2021 Jul 21;10(7):805-814.
https://doi.org/10.1530/EC-21-0265

III. Klironomos S, Sjöström A, Tzortzakakis A, Martin Muñoz DA, Martin H, Lundberg J, Falk Delgado A, Nelson DW, Granberg T. Neurohypophyseal MRI abnormalities highlighting the role of vasopressin in sodium dysregulation in COVID-19. [Submitted]

IV. Sjöström A, Markgren PO, Hansson M. Prognostic potential of creatinine and Cystatin C in COVID-19 - a retrospective cohort study from Karolinska University Hospital. Scand J Clin Lab Invest. 2023 Jul;83(4):251- 257.
https://doi.org/10.1080/00365513.2023.2210291