Table 1.

Role of eosinophils in respiratory viral infections.

Virus	Model	Major findings	Mechanism of action	References
RSV	Human: In vitro: peripheral blood eosinophils.	RSV can infect human eosinophils. Eosinophils internalize and inactivate RSV, and are activated by the virus.	Release of IL-6, IL-1α, IL-13, IL-15, G-CSF, and GM-CSF. Upregulation of CD69 and CD11b expression.	(66) (104) (59)
	Mouse: In vitro: bone marrow-derived eosinophils. In vivo: Intranasal injection of RSV in mice.	↓ Viral load; ↑ Eosinophils accumulation; ↑ CD11b; ECP release; production of NO; antiviral immunity.	TLR-7, CD11b, ECP, NO. Antiviral immunity through NO production, clearance of RSV via MyD88-dependent pathways, reduction of RSV-induced mucus hypersecretion.	(59) 85)
IAV	Mouse: In vitro: peripheral blood and bone marrow-derived eosinophils In vivo: Transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into IAV-infected mice.	Acute asthma infected mice: ↑ numbers of eosinophils in the airways, faster virus clearance, ↑ CD8+ T cells and lower epithelial damage. Adoptive transfer of eosinophils: ↓ viral burden and ↑ CD8+ T cell numbers in the airways of recipient mice.	In vitro: Piecemeal degranulation, NO release, ↑ MHC-I and CD86, induction of CD8+ T cell responses by virus pulsed eosinophils.	(95) (76)
PIV	Human: In vitro: IFN-γ preincubated human eosinophils.	Eosinophils significantly decreased PIV titers.	TLR-MyD88 pathway. In vitro: NO generation through TLR-7, PIV human eosinophils infection is abortive.	(101)
	Mouse: IL5 transgenic mice, PIV infection, anti-IL5 antibodies treatment. Guinea pig: sensitization to a non-viral antigen, infection, anti-IL5 antibodies.	↑ Eosinophils in the lungs; ↓ viral content in the lungs; sensitization to a non-viral antigen leads to an eosinophil-mediated ↓ viral content in the lungs.	TLR-7 involvement and NO production	(100) (99)
HRV	Human: In vitro: peripheral blood eosinophils.	Eosinophils as APCs: induction of CD4+ T-cell proliferation and IFN-γ production.	Viral binding through ICAM-1, cooperation between T cells and eosinophils: T cells secreted IFN-γ leads to ↑expression of TLR-7 and TLR-8 on eosinophils.	(103)
	Human: anti-IL5 antibody treatment, HRV infection.	Eosinophils depletion leads to increased viral loads in nasal swabs.	↑ CD69 expression	(104) (105)
SARS-CoV-2	Human	↓ Eosinophils absolute count (EC) associated with higher mortality.	Unclear, likely multifactorial.	(18) (114) (110) (36)
		↑ EC correlate with immune recovery ↑ EC correlate with milder clinical course and better disease outcomes	Th2-specific pathways Lower level of C-reactive protein, role in mitigating the severity of inflammatory response.	(117) (113)
		Protective role of eosinophils against severe COVID-19 illness even if associated to allergic asthma.	Possible protective mechanisms of asthma and type 2 inflammation on COVID-19 infection, expression of SARS-CoV-2 entry receptors, antiviral activity of eosinophils and cross-reactive T-cell epitopes.	(111) (109) (124)
		Subset of eosinophils related to clinical deterioration Immune exhaustion of eosinophils and inhibition of Th2-mediated immune response	IFN-γ-mediated upregulation of CD62L on eosinophils precedes lung hyperinflammation. ↑ expression of the programmed death receptor ligand 1 (PD-L1) checkpoint and ↓ expression of CRTH2 (CD294).	(124) (125)
		Algorithms using eosinophil counts to predict disease severity and to make a differential diagnosis.	“COVID-19-REAL” risk stratification score used to identify patients who are likely to be presenting with COVID-19 “PARIS” score categorizes the pre-test probability of SARS-CoV-2 infection (eosinophil counts < 60 / µL) Blood eosinophil counts (< 0.01 × 109/L) distinguishes between COVID-19 and influenza virus infection.	(119) (120) (121)
		Dysregulation of immune responses in Long-COVID patients.	Persistently activated eosinophils ↓ counts, activation and hyper-responsiveness up to 6 months after active disease	(126) (127)

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