Table 2.

Risk factors for Long-COVID.

Risk factors	Possible effects on Long-COVID	Reference
SARS-CoV-2 infection	The infection of SARS-CoV-2 can cause cell death and immune dysfunction, which is the direct reason to cause the long-term effects on human organs and brains. Around 10% of people infected with SARS-CoV-2 are estimated to have Long-COVID.	[2, 107]
Cytokine storm	SARS-CoV-2 can activate the immune system through TLR, RLRs, and NRSs signaling to produce cytokines and induce cell death. Dysregulated release of cytokines can conversely cause cytokine storms to lead severe diseases to exacerbate the symptoms of Long-COVID.	[71, 108]
Syncytia	The fusion activity of spike protein of SARS-CoV-2 with host cells can trigger multiple cell fusion in infected organs, which can induce cell death, hyperimmune responses, and the long-term symptoms during the recovery from SARS-CoV-2 infection.	[46, 51]
Autoantibodies	Autoantibodies against type I IFN increase the risk of sever COVID-19 and result in novel type of acquired immunodeficiency, which can prolong the symptoms of Long-COVID.	[90, 109]
Microclots	Microclots can induce autoantibodies in infected organs, which can cause the long-term effects on recovery from SARS-CoV-2 infection.	[90, 110]
Persistent viral infection	It can keep the persistent stimulation on host immune responses and viral protein expression. Spike protein only could induce neuroinflammatory and behavioral sickness responses.	[86, 87]
Biopsychosocial effects	COVID-19 symptoms are associated with emotion stress in some patients, which might be related to the biopsychosocial effects after patients infected with SARS-CoV-2. Biopsychosocial factors might contribute to the fare of COVID-19 and thus affect the recovery from Long-COVID.	[92, 111]