Mesenchymal stem cells and their derived exosomes for the treatment of COVID-19

Table 1 Advantages and disadvantages of existing coronavirus disease 2019 treatment approaches

Treatment categories	Classification	Application examples	Countries and regions	Advantages	Disadvantages
Targeting the host response	Inflammation	Dexamethasone reduces overreaction of the immune system and lowers inflammation[118]	Widely used globally	Reduces the immune system’s overreaction and lowers inflammation, decreasing mortality rates	There are uncertainties and individual variabilities, which may entail potential risks and are constrained to early disease intervention
	Thrombosis	Heparin is used to prevent thrombosis and protect the cardiovascular system[119,120]		Reduces the risk of thrombosis and improves the prognosis of patients	Blood clotting needs to be carefully monitored to reduce the risk of bleeding
	Acute respiratory distress syndrome	Oxygen therapy aids in supporting respiratory function and enhancing oxygenation[121,122]		Improves severe hypoxemia	There are side effects on healthy organs and tissues
	Activation of the renin-angiotensin-aldosterone system	ACE inhibitors alter ACE2 expression or activity[123,124]		Reduces the viral invasion by SARS-CoV-2, thus improving survival and reducing lung inflammation and injury	There is a potential risk of causing or exacerbating hypotension, hyperkalemia, or kidney damage
	Multi-targeted stem cell therapy	Stem cell therapy promotes the repair of damaged tissue, regulates immune responses, and reduces inflammation[125]		Decreases the inflammatory response, lowers the risk of cytokine storms, and promotes the repair of damaged tissues, thereby improving outcomes in severe cases	Further research is necessary to ascertain the safety, efficacy, optimal timing for administration, and appropriate dosages
Targeting viruses	Blocking viral replication	Artemisia annua, through its direct inhibition of viral RNA polymerase[5]	Madagasca (Africa)	Offers a potential for shorter hospitalization	The use of unproven artemisinin therapy raises concerns about the emergence of drug-resistant malaria. For drugs currently in use, there should also be extensive randomized controlled trials to assess their effectiveness and safety in the population
		The active metabolite of remdesivir reduces genome replication by inhibiting RNA-dependent RNA polymerase[4]	Widely used globally
	Blocking viral access to host cells	Plasma from convalescent patients containing antibodies against SARS-CoV-2[126-128]	United States, United Kingdom, Germany, China, Brazil, Africa, etc.	Provides immediate immune support and benefits critically ill patients who do not have other appropriate treatment options. Early administration of recombinant monoclonal antibody is effective in preventing hospitalization	However, challenges include high variability in antibody levels and quality, the need to match blood types, and the risk of transmission of other pathogens. The neutralizing activity of recombinant monoclonal antibodies is readily lost as new virus variants emerge
		Passive administration of pathogen-specific antibodies has been employed to control viral infections[129-132]
Targeting improves immunity	Nutritional supplement	Vitamin C enhances immunity by stimulating interferon production and lymphocyte proliferation and enhancing neutrophil phagocytosis[133]	Widely used globally	Enhances immunity	Further research is needed to fully understand its safety, efficacy, optimal administration timing, and dosage

SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; ACE2: Angiotensin-converting enzyme 2.