Table 1.

Summary of studies which reported altered cytokine levels and immune functions in patients with SARS-CoV infections and related conditions.

Disease	Case/Control	Sample	Finding		Comment	Ref
			Cytokines	Immune cells
SARS-CoV-2	40 cases:13 Severe, 27 mild	Blood	Elevated IL-6, IL-10, IL-2, IFN-γ levels in severe cases	Increased neutrophil, decreased lymphocyte counts esp. CD8 + T in severe cases	N8R ratio as a as a prognostic factor	[8]
	99 cases	Blood	Increased IL-6	Increased leucocytes, neutrophils, decreased lymphocytes	–	[9]
	41 cases: 13 ICU/ 28 non-ICU patients	Plasma	Elevated IL-10, IL-2, IL-7, GSCF, IP10, MCP1, MIP1A, and TNFα in ICU patients	–	–	[3]
	100 cases: 34 mild, 34 severe, 32 critical	Blood	A significant association between IL and 6, IL-10, IL2R, IL-8, TNFα, CRP, ferroprotein, procalcitonin, and disease severity	A significant association between WBC, lymphocyte, neutrophil and eosinophil counts and disease severity	IL-6, TNFα, IL-8 as promising therapeutic targets	[7]
	53 cases:34 severe, 19 mild	Plasma	Association of IP-10, MCP-3, IL-1ra with disease severity	–	–	[6]
	123 cases:21 severe, 102 mild	Blood	Elevated IL-6 and IL-10 in severe NCP	Decreased CD4 + T, CD8 + T in severe NCP	T cell subsets and cytokines as predictive factors for severity.	[7]
MERS	Case report of a child with influenza associated MERS	CSF and serum	Elevated IL-10 and IFN‐γ in early phase in CSF	–	–	[21]
	MERS infected cells/SARS infected cells	Calu-3 cells	Higher IL-1β, IL-6 and IL-8 induced by MERS, higher TNF-α, IFN-β and IP-10 induced by SARS-CoV	–	Delayed proinflammatory cytokine induction by MERS-CoV	[15]
	MERS-infected MDMs/SARS infected MDMs	MDM cells	Elevated TNF-α, Il-10 in both cells, higher MERS induced IL-8, IL-12, IFN-γ, IP-10/CXCL-10, MCP1/CCL-2, MIP-1α/CCL-3, RANTES/CCL-5	–	None of the viruses were able to induce IFN-α and IFN- β.	[17]
	17 cases	Serum	Elevated IL-6 and CXCL-10	–	Elevated serum levels of IL-6 and CXCL-10 in severe patients	[16]
	7/13	Plasma	Elevated IFN-γ, TNF-α, Il-10, IL-15 and IL-17	–	MERS induced Th1 and Th17 cytokine profile	[18]
	14 cases: 4 groups based on severity	Plasma	Elevated IFN-α, G-CSF, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12, IL-15, IL-17A, IFN-γ, TGF-β, MCP-1 (CCL2), IP-10 (CXCL10), MDC (CCL22), RANTES (CCL5), IL-8 (CXCL8), MIP-1 (CCL3), Eotaxin (CCL11), and GRO (CXCL1)	Increased lymphocytes, neutrophils, leukocytes and monocytescounts	IL-10, IL-15, TGF-β, and EGF were correlated with disease severity	[22]
SARS	8 children before corticosteroids therapy/after 1–2 days/after 7–10 days	Plasma	Elevated IL-1β -before and 7–10 days after therapy,decreased IL-10, IL-6, IL-8	–	TNF-α was not significantly elevated thus TNF-α monoclonal antibody was not recommended.	[13]
	SARS infected cells / cells infected with RSV, FluAV, and hPIV2.	Caco2 cells	Induced high levels of IL-6, IFN-β, TLR4, TLR9	–	–	[23]
	88 cases 51 Ab positive/37 Ab negative	Serum	Elevated IFN- γ, IL-18, TGF- β, IL-6, IP-10, MCP-1, MIG, and IL-8	–	IFN- γ induced cytokine storm after viral infection	[24]
	20 cases	Plasma	Elevated IL-1, IL-6, IL-8,IL-12, IFN-γ, MCP-1, IP-10	Accumulation of monocytes/macrophages and neutrophils	Th1 cell‐mediated immunity and hyperinnate inflammatory response in SARS.	[12]
	228 cases	Serum	Elevated IL-6, decreased IL-8 and TGF-β	–	Elevated IFN-γ, IL-4 and decreased IL-10 only in convalescent SARS patients.	[14]
	61 cases:initial stage, peak stage, remission,recovery stage / 44 Healthy control	Serum	Elevated IL-6, IL-8, TNF-α, IL-16, TGF-β1, decreased IL-18	–	The mean concentration of IL-13 gradually decreased from initial stage to recovery.	[25]
Influenza	–	HMC	IL-1β mRNA expression was induced by influenza A and Sendai viruses.	–	Virus induced IL-1β and IL-18 expression and activation is related to cellular differentiation and caspase-1-dependent pathway.	[19]
	19 cases	Nasal lavage fluid, plasma, serum	Elevated IL-6, IL-8, IFN-α	–	–	[26]
	–	Human primary alveolar and bronchial epithelial cells	IP-10, IFN-β, RANTES, IL-6	–	–	[27]
	77/17	Nasal lavage fluid	Lower IL-6	Lower monocyte counts	Pro-inflammatory cytokines levels were not elevated in patients with pneumonia.	[20]
ARDS	51 casesat the time of ECMO installation/ 6  h later	Plasma	Elevated IL-10 and IL-8 levels	Higher Treg, CD14 + CD16+, CD14 + TLR4 + cell counts in survivors	IL-10 levels predict ICU mortality.	[28]
	300/300	Plasma	Higher TNF-α, IL-6 levels in patients	–	Functional polymorphisms in TNF-α, IL-6, MyD88 are associated with ARDS mortality.	[29]
Pneumonia	15 severe/15 non-severe CAP	Blood	Elevated IL-6, IL-10, IL-8, CRP levels	–	IL-6 sharp decrease was associated with response to empirical antibacterial treatment by day 3.	[30]
Septic shock	Endotoxin-stimulated septic monocytes/normal monocytes	Serum	Elevated IL-10, attenuated TNF-α in septic serum	–	The persistent release of IL-10 leads to impaired proinflammatory cytokine release and the immune dysfunction in septic shock.	[31]
	16 septic shock/ 11 circulatory shock	Plasma	More increased IL-10 in septic shock cases	–	The production of the IL-10 positively correlates with the intensity of the inflammatory response in septic shock.	[32]
Febrile illness	464 cases431 survived/ 33 dead	Plasma	Higher IL-10 and lower TNFα in patients who died	–	IL-10 to TNFα ratio was associated with mortality of CAI.	[33]

Severe acute respiratory syndrome coronavirus 2, Neutrophil-to-CD8 + T cell ratio (N8R), 2019 novel coronavirus pneumonia (NCP), Human Macrophage Cell (HMC), human monocyte–derived macrophages (MDMs), human monocyte-derived dendritic cells (DCs), SARS sera antibody (Ab positive), cerebrospinal fluid (CSF), Acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO), community-acquired pneumonia (CAP), community-acquired infection (CAI).