Table 2.

A. Characteristics of the included studies B. Outcomes of the individual studies

Reference	Study design	Country	Sample size	Age, yMean ± SD or Median (IQR)	Disease severity	Intervention
Hendawy et al.[27]	case series	Egypt	2	50 (min-max: 40-60)	Hospitalized, severe illness	Ozonized rectal insufflation +standard therapy
Franzini et al.[28]	case series	Italy	50	75 ± 11.4	Hospitalized, severe illness	Major autohemotherapy + standard therapy
Hernandez et al.[29]	case series	Spain	3	61 (min-max: 49-64)	Hospitalized, severe illness	Major autohemotherapy + standard therapy
Wu et al.[30]	case series	China	4	60 (54.5-70.5)	Hospitalized, mild to severe illness	Major autohemotherapy + standard therapy

Reference	Clinical improvement		All-cause mortalityN (%)	Length of Hospital Stay(Mean ± SD)	Laboratory outcome(Mean ± SD / Median)		Any adverse eventsN (%)
	Baseline	Outcome			Baseline	Outcome
Hendawy et al.[27]	•Temp. 38 0C •RR 50x/min •HR 120x/min •SaO2 60% room air, 90% (FiO2 90%)	•2h: SaO2 96% (FiO2 90%) •4h: HR 95x/min •24 h: RR 28x/min, HR 90x/min, SaO2 94%(FiO2 60%) •48 h: RR 28x/min, HR 94x/min, SaO2 94%(FiO2 50%) •96h: RR 16x/min, HR 84x/min, SaO2 95%(FiO2 28%)	0 (0%)	N/A	N/A	N/A	0 (0%)
	•Temp. 38-38.5 0C •RR 30x/min •HR 110x/min •SaO2 85% room air, 95% (simple mask 5l/min)	•4h: SaO2 95% room air, RR 17x/min, HR 94x/min
Franzini et al.[28]	•Temp.: 37.7-38.7 0C •HR(x/min): 90-100 •SaO2: 80-85%	•Temp.: 36-36.5 0C •HR (x/min): 70-75 •SaO2: 90-95%*	2 (4%)	22.13 ± 3.44	●Fasting glucose (mg/dL): 200-250 ●ALT (IU/L): 90-100 ●Creatinine (mg/dL): 1.5-3 ●WBC (n/μl): 3000-4000 ●CRP (mg/dL): 10-15 ●IL-6 (IU/L): 25-660 ●LDH (IU/L): 300-350 ●PCT (ng/ml): ≤ 0.5	●Fasting glucose (mg/dL): 120-150 ●ALT (IU/L): 40-50* ●Creatinine (mg/dL): 1.0-1.3 ●WBC (n/μl): ≥ 5500 ●CRP (mg/dL): ≤ 5* ●IL-6 (IU/L): ≤ 100** ●LDH (IU/L): ≤ 300* ●PCT (ng/ml): ≤ 0.05*	NR
					●Lowering of D-dimer 50.617% ± 21.904 from baseline
Hernandez et al.[29]	•P/F ratio 235 •FiO2 0.8	•P/F ratio N/A •FiO2 0.31	0 (0%)	3.67 ± 0.58	●Ferritin 1609 ng/ml ●D-dimer 1900 ng/dl ●CRP 17.3 mg/dl ●LDH 536 IU/l	●Ferritin 7d: 246 ng/ml ●D-dimer 7d: 323 ng/ml ●CRP N/A ●LDH N/A	0 (0%)
	•P/F ration 253 •FiO2 0.6	•P/F ratio 290 •FiO2 0.31			●Ferritin 2200 ng/ml ●D-dimer 3660 ng/dl ●CRP 10 mg/dl ●LDH 816 IU/l	●Ferritin N/A ●D-dimer N/A ●CRP 5d: >0 mg/dL ●LDH 5d: 469 IU/l
	•P/F ration 243 •FiO2 0.8	•P/F ratio N/A •FiO2 N/A			●Ferritin 656 ng/ml ●D-dimer 657 ng/dl ●CRP 5 mg/dl ●LDH 452 IU/l	●Ferritin N/A ●D dimer 6d: >100 ng/ml ●CRP 6d: >0 mg/dL ●LDH N/A
Wu et al.[30]	P/F ratio: 80	P/F ratio: 362	0 (0%)	22 ± 7.87	NA	NA	0%
	P/F ratio: 423	P/F ratio: 405			NA	NA
	P/F ratio: 410	P/F ratio: 306			NA	NA
	P/F ratio: 575	P/F ratio: 412			NA	NA

N/A: not available; SD, standard deviation; RR, respiratory rate; HR, Heart rate; CRP, c-reactive protein; LDH, lactate dehydrogenase; WBC, white blood cells; IL, Interleukin; PCT, pro-calcitonin; ALT, alanine transaminase; LFT, liver function test; * p<0.05; ^** p<0.001

SD, standard deviation; IQR: inter-quartile range