Table 1.

Biomarkers in the modes of cell death in COVID-19.

Cell death modes	Biomarkers	Functions	References
Necroptosis	RIPK3	The serum RIPK3 level is high in COVID-19 patients in severe cases but does not directly indicate necroptosis.	(72)
	MLKL	Robust phosphorylation of MLKL shows that necroptosis occurs.	(77)
	IL-1β	Demonstrates the development and severity of COVID-19.	(28, 78)
	RIPK1	Elevated RIPK1 levels show apoptosis or necroptosis, or both.	(70)
Ferroptosis	F4-hydroxynonenal (4-HNE) Cytotoxic malondialdehyde	Product of ferroptosis lipid peroxide degradation. Cytotoxic and damage heart cells, resulting in cardiac dysfunction and heart failure.	(79, 80)
	Serum ferritin	Increase related to severity and mortality risk in COVID-19 patients.	(6, 81)
	Transferrin receptor (TfR)	TfR expression plays a bridge role between iron overload and the gender and age difference in the severity of COVID-19.	(82)
	Total iron, nonheme iron in the lavage fluid, and intracellular Tf and lactoferrin (Lf)	Increase in Acute Respiratory Distress Syndrome (ARDS) patients.	(83)
Pyroptosis	IL-6	Significant increase in non-survivors vs. survivors and severe vs. non-severe disease; connected to cytokine storm, additional tissue damage, and multiple organ failure (MOF).	(84)
	ASC	Forms the NLRP3 inflammasome.	(85)
	IL-1β	The most severe patients are correlated with increased pro-inflammatory cytokines, evocative of a cytokine storm.	(85)
	IL-18/IFN-γ	Activates macrophages, resulting in multiple cytokine release, hemophagocytosis, coagulopathy, and ARDS.	(86)
	miRNAs (miR-223-3p)	Regulates the NLRP3 inflammasome and acts at a priming and activation level of NLRP3 formation.	(87)

ASC, Apoptosis-associated speck-like protein containing a caspase recruitment domain; COVID-19, Coronavirus Disease 2019; IFN, interferon; IL, interleukin; MLKL, mixed lineage kinase domain-like pseudokinase; NLRP3, NLR family, pyrin domain containing 3; RIPK1, receptor-interacting protein kinase 1; RIPK3, receptor-interacting protein kinase 3.