Growth differentiation factor 15 as an emerging novel biomarker in SARS-CoV-2 infection

Table 1 Studies included in the systematic review, with duration, type, region/place, and main findings

Refs	Study duration	Type of study	Region/place	Main findings
Myhre et al[23], 2020	March 18, 2020 to May 4, 2020	Prospective, observational study	Norway	GDF-15 has a better prognostic significance than recognized inflammatory biomarkers like CRP, ferritin, procalcitonin, and IL-6
Notz et al[24], 2020	March 14 to May 28, 2020	A single-center retrospective study	Germany	There was no evident imbalance of pro-and anti-inflammatory pathways, with higher GDF-15 levels in patients with SARS-CoV-2 infection during ICU stay, implying elevated tissue resilience
Luis García de Guadiana Romualdo et al[25], 2021	March 14 to April 12, 2020	Case-series	Spain	The GDF level was significantly high in nonsurvivors compared to survivors of SARS-CoV-2 infection, and it may be useful to predict prognosis
Teng et al[26], 2021	January 22, 2020, to May 13, 2020	Retrospective study	China	GDF-15 could be used as a biomarker to predict the severity of SARS-CoV-2 infection. GDF-15 level increased consistently with increased severity of SARS-CoV-2 infection, and GDF-15 expression returned to normal level similarly in a convalescent group compared to the healthy control participants. Hence, it implies that the GDF-15 precisely monitors the progression of SARS-CoV-2 infection
Kanberg et al[27], 2021	February 21 to November 5, 2020	Prospective study	Sweden	Patients with severe and moderate SARS-CoV-2 infection exhibited significantly increased GDF-15 levels compared with participants with mild infection and controls throughout the acute phase. Even after 6 mo of infection, GDF-15 concentrations persisted considerably higher in the severe and moderate infections compared to patients with mild infection and controls
Ebihara et al[28], 2022	August 2020 to December 2020	Prospective multicenter observational study	Japan	GDF-15 may be beneficial to predict delayed recovery or mortality of SARS-CoV-2-infected patients during ICU treatment
Alserawan et al[29], 2021	Not mentioned	Prospective study	Spain	GDF-15 may play a role in categorizing SARS-CoV-2-infected patients based on severityGDF-15 is an excellent biomarker to detect impaired respiratory function compared to CRP and D-dimer

CRP: C-reactive protein; GDF-15: Growth differentiation factor 15; IL-6: Interleukin 6; ICU: Intensive care unit; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.