Table Info

Table 2.

Efficiency of anti-inflammatory drugs

Type of anti-inflammatory drugs	Anti-inflammatory drugs	Dosage	Duration (day)	Outcomes	References
Glucocorticoids	Hydrocortisone, methylprednisolone, or dexamethasone	80 mg of methylprednisolone sodium succinate per day for the first 3 days, followed by 40 mg per day during the following 3 days, and 20 mg per day for another 3 days before being discontinued One patient took it at the dosage of 40 mg per day for 5 days and 20 mg per day for another 5 days	9 or 10	Fever disappeared, clinical symptoms improved, chest computed tomography (CT) manifestations improved, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid turned negative	[100]
		Median hydrocortisone-equivalent dose of 400.0 mg/day	The average time is 9.5 days	Improved oxygen saturation (SaO₂) and arterial oxygen tension (PaO₂)/inspiratory oxygen fraction (FiO₂) in the first 3–5 days, inhibited furious inflammatory storm treated in the phase of acute respiratory distress syndrome (ARDS). No benefit for increasing survival rate	[99]
		1–2 mg/kg/day via intravenous injection	5–7	Accelerated the improved time of SpO₂, accelerated the decreasing of the levels of C-reactive protein (CRP) and IL-6, shortened the duration time of ICU and hospitalization significantly, improved chest CT manifestations significantly	[97]
		-	3	Cough was relieved and chest CT manifestations were improved after 3 days of treatment, however, lymphocytes were still reduced, and the erythrocyte sedimentation rate was increased. Fever reoccurred accompanied by a paroxysmal cough, and the whole body’s skin was flushing. CT manifestation images showed exacerbated pneumonia. No benefit for SARS-CoV-2 shedding	[98]
Statins	Atorvastatin, etc.	-	-	Statin was associated with decreased mortality in patients with COVID-19 [relative risk (RR) 0.72 (0.55, 0.95), P = 0.018; I-squared statistic (I²): 84.3%, P < 0.001]. The association of statin and mortality was not significantly affected by age, male gender, diabetes, and hypertension in this pooled analysis	[107]
Statins	Atorvastatin, etc.	-	-	Inpatient statin use was associated with a significant reduction in mortality among COVID-19 patients especially those with diabetes mellitus (DM). Diabetic patients who received inpatient statins had significantly reduced mortality [odds ratio (OR), 0.35; 95% confidence interval (CI), 0.21–0.61; P < 0.001], reduced need for ICU admission (OR, 0.56; 95% CI, 0.34–0.90; P = 0.02) as well as a decreased need for mechanical ventilation (OR, 0.39; 95% CI, 0.23–0.65; P < 0.001)	[109]
Ivermectin	Tocilizumab	Ivermectin 6 mg stat and doxycycline 100 mg twice daily	5	Early improvement 60.7% vs. 44.4%, P < 0.03, deterioration 8.7% vs. 17.8%, P < 0.02	NCT04523831
		8 mg/kg by two consecutive intravenous infusions 12 h apart, a third infusion was optional based on clinical response	10	Improved respiratory functions, improved chest X-ray manifestations, 15% patients discharged from the hospital, improved the inflammatory status Adverse effects: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive on day 10	[119]
		400 mg per time or 600 mg per time, median total dose of 5.7 mg/kg	14	Increased the rate of cases relieved fever, increased the rate of cases decreased the level of CRP, the rate of cases need oxygen support from 84% decreased to 28%, 68% cases improved chest CT manifestations Adverse effects: 92% patients experienced at least one adverse event, the most frequent adverse events were anemia (16.64%), alanine aminotransferase (ALT) rise (11.44%), and QT interval prolongation (5.20%)	[120]
		4 mg/kg (400 mg), single infusion	-	Within 24 h, the patient’s oxygenation and hemodynamics improved, as evidenced by a pressure of oxygen to the FiO₂ (P/F) ratio of 246. The patient was discharged on day 14 after the infusion of tocilizumab	[121]
		162 mg single dose	-	Fever disappeared in two days after the treatment of tocilizumab; the level of IL-6 was improved in a week after the treatment of tocilizumab; decreased the need for oxygen support; CT manifestation images showed improvement in pneumonia	[122]
		8 mg/kg, one dose	-	The patients improved rapidly after the treatment of tocilizumab; there is no need for oxygen support after 4 days of the treatment of tocilizumab; the patient was allowed discharged from ICU after 4 days of the treatment of tocilizumab; CT pulmonary angiography showed pneumonia improved	[123]
		First dose was 4–8 mg/kg body weight, and the recommended dose was 400 mg through an i.v. drip up to a maximum of 800 mg	-	75% patients decreased the need for oxygen support in 5 days after the treatment of tocilizumab; CT manifestations of 90.5% patients showed pneumonia improved; the percentage of lymphocytes in peripheral blood was increased after the treatment of tocilizumab; abnormally elevated CRP decreased significantly in 84.2% patients; all patients have been discharged on average 15.1 days after giving tocilizumab	[124]
		8 mg/kg, with a second dose 12 h after the first and a possible third dose after a further 24–36 h, according to clinical response	-	The fever of the two cases disappeared in 3 days after the treatment of two dose tocilizumab, improved clinical status, improved the respiratory function, decreased the level of CRP to normal, consecutive test of SARS-CoV-2 nucleic acid of one case showed negative	[125]
		8 mg/kg, 2 doses, 12 h apart	-	Decreased CRP level and white blood cell count in 24 h after the treatment of tocilizumab; patient clinical condition progressively improved and ventilatory support was gradually weaned; chest CT showed mark improvement of CT findings on day 7 after the treatment of tocilizumab	[126]
		8 mg/kg, no more than 800 mg per time	-	Inflammation level was not significantly decreased, and lymphocyte and prothrombin time did not improve in the 3 patients treated with tocilizumab	[127]
		1 or 2 dose	-	Reduced death rate, reduced the duration time of ICU admission	[128]
		324 mg via subcutaneous route	-	Fever disappeared, arterial pO₂ showed progressive improvement and oxygen treatment was stopped after the treatment of tocilizumab; IL-6 levels were increased at 6 days after administration of tocilizumab	[129]
		8 mg/kg tocilizumab (maximum dose 800 mg/day) repeated within 12 h from the first administration	-	Fever disappeared after the treatment of tocilizumab, decreased the level of CRP Adverse effects: high prevalence of candidemia occurred in the patients treated with tocilizumab in a very short period of time	[130]
Cytokine inhibitors	Sarilumab	400 mg was injected intravenously, one or two dose	-	Accelerated the clinical improvement time of COVID-19 patients with lung consolidation < 17%	[132]
	Sarilumab	400 mg was injected intravenously, one or two dose	-	10 out of 15 critical ill COVID-19 patients survived, 5 patients were died; improved inflammatory status	[133]
	Siltuximab	11 mg/kg was injected intravenously over one hour, or a second dose was injected depending on the patient’s condition	-	Reduced 30-day mortality of COVID-19 patients significantly, 16 out of 30 patients were discharged, 10 out of 30 patients were died	[135]
	Olokizumab	160 mg/mL 0.4 mL was injected intravenously, one dose	-	Decreased CRP level significantly, improved clinical parameters	[136]
	Anakinra	Anakinra was administrated subcutaneously at 100 mg/12 h from day (D) 1 to D3, then at 100 mg/24 h from D4 to D10	10	Relieved fever in three days after the treatment of anakinra, improved respiratory function and inflammatory conditions, decreased the level of CRP and the level of 5/8 patients recovered to normal on day 11 from admission, the extension of lesions had stopped	[138]
		100 mg three times a day or 200 mg intravenously twice a day	Case 1 was stopped to take it at the next due to improved respiratory functions, 7 days for case 2, and 10 days for case 3	Improved respiratory functions, relieved fever, decreased the level of ferritin, improved pneumonia status and clinical conditions	[139]
		100 mg every 8 h (300 mg/daily) for 24 h to 48 h, followed by tapering, according to clinical response	6–13	All 5 patients experienced rapid resolution of systemic inflammation, and remarkable improvement in respiratory parameters, with the reduction of oxygen support requirement and early amelioration of chest CT scan abnormalities before discharge in 3 patients. All patients were discharged 6 to 13 days after the start of anakinra. No secondary infections or other adverse events were observed	[140]
		100 mg subcutaneously every 6 h	The maximum time is 19 days	Of the 14 patients who met the criteria, 11 patients received anakinra for a maximum of 19 days. Seven of the patients who started anakinra treatment ≤ 36 h after the onset of acute hypoxemic respiratory failure did not require mechanical ventilation, and all were discharged home. Four patients who started anakinra ≥ 4 days after the onset of acute hypoxemic respiratory failure required mechanical ventilation. Of those, 3 patients were extubated (2 discharged home and 1 remained hospitalized), and 1 died	[141]
		150 mg two times per day	7	Reduced the need for oxygen support, relieved fever, significantly reduced the level of ferritin and CRP with 48 h after the treatment of anakinra, improved respiratory functions and blood parameters after 7 days treatment of anakinra	[142]
		100 mg twice a day for 72 h, then 100 mg daily for 7 days	10	Need for invasive mechanical ventilation or death occurred in 13 (25%) of 52 patients in the anakinra group compared with 32 (73%) of 44 patients in the historical group. Among the 39 patients in the anakinra group, the need for oxygen was decreased; decreased the level of CRP; a higher rate of cases had an increase in liver aminotransferase (more than three times the upper limit of normal); a higher rate of cases developed a thromboembolic event during the hospital stay; seven (13%) had a pulmonary embolism, three (6%) had deep vein thrombosis of the lower limbs, and one (2%) had arterial thrombosis in the anakinra group; none of the patients in the anakinra group had a documented bacterial infection during the hospital stay	[143]
	Mavrilimumab	6 mg/kg injected intravenously, one dose	-	Increased clinical improvement rate significantly, accelerated the time of clinical improvement and fever resolution	[144]
	Mavrilimumab	6 mg/kg injected intravenously, one dose	-	No significant difference in survival rate	[145]
C5a antibody	Eculizumab	900 mg per time, two doses	-	Improved inflammatory status, all laboratory tests were better when the cases were discharged; decreased the level of CRP, improved CT manifestations	[146]
		900 mg per week	At most three weeks	Higher level of PaO₂ and the ratio of PaO₂/FiO₂, decreased the level of D-dimer, increased platelet counts, improved CT manifestations, decreased the duration time of hospitalization	[147]
		900 mg per time or 1,200 mg per time	-	Significantly reduced the level of D-dimer and neutrophil counts; liver function and creatinine were normalized; severe heart failure and acute kidney injury had remissions; one case was died for respiratory failure	[148]
Chemokine receptor 5 (CCR5) antibody	Leronlimab	700 mg was injected subcutaneously, second dose was injected on Day 7	-	IL-6 levels and inflammatory status were recovered; plasma viremia reduced	[149]
Chemokine receptor 5 (CCR5) antibody	Leronlimab	700 mg was administered via two abdominal subcutaneous injections of 350 mg each, with repeat dosing if they remained hospitalized after 7 days	-	17 out of 23 patients were recovered, and 4 out of 23 patients were died in 7 days. Reduced IL-6 level, CRP level was decreased dramatically after the second dose of leronlimab	[150]
CD6 antibody	Itolizumab	1.6 mg/kg totally	14	7 out of 20 patients in the treatment arm did not survive and the 1-month mortality rate was 35%, compared to the 1-month mortality of 60% in the control arm (130 patients)	[152]
Janus kinase (JAK) inhibitors	Ruxolitinib	10 mg twice a day	11	Reduced the need for oxygen support, inhibited the proliferation of SARS-CoV-2 in blood, decreased the level of IL-6 and ferritin	[154]
	Ruxolitinib	Started with 5 mg twice daily, the dosage was increased to 10 mg BID after 24–48 h in case there was no improvement of respiratory function and/or oxygen support from baseline, provided no adverse event ≥ grade 3 was observed; further escalation to 25 mg daily was allowed after an additional 48 h	28 days, the median time is 13 days	85.3% patients were discharged, 82.4% patients gained clinical improvement, 67.6% cases were PCR-negative on double check of upper respiratory tract swab at a median of 21 days after initiation of treatment with ruxolitinib, improved the frequencies of interferon (IFN)-γ producing T cells and TNF-α producing NK cells, improved inflammatory status, decreased the increased level of CRP induced by COVID-19 Adverse effects: anemia, urinary tract infection, increase of creatinine, thrombocytopenia, increase of aminotransferases. Three thrombotic events were recorded: pulmonary embolism, brachial vein thrombosis following the positioning of the venous catheter, and peripheral arterial thrombosis	[155]
	Baricitinib	4 mg/day	2 weeks	Fever, SpO₂, PaO₂/FiO₂, CRP, and Modified Early Warning Score (MEWS) significantly improved, all clinical characteristics and respiratory function parameters significantly improved and CRP values significantly decreased both at week 1 and week 2, increased the rate of cases discharged	[156]
	Tofacitinib	10 mg twice daily	14	Increased survival rate of COVID-19 patients significantly when compared to the treatment of dexamethasone only	[158]
BCR-ABL1 inhibitor	Imatinib	400 mg once daily	5	Fever relieved; clinical symptoms improved and disappeared; blood tests turned out to be normal; pulmonary opacities had almost disappeared	[167]
Bruton tyrosine kinase (BTK) inhibitors	Acalabrutinib	100 mg orally or per enteric feeding tube twice daily	10 days for patients on supplemental oxygen or 14 days for patients on mechanical ventilation	Increased SaO₂, absolute lymphocyte count, and decreased CRP	[169]
Bruton tyrosine kinase (BTK) inhibitors	Ibrutinib	420 mg/day	The median time was 52 months	No dyspnea was observed in 5 COVID-19 patients with Waldenström macroglobulinemia, they did not require hospitalization. Oxygenation improved, and CRP levels decreased were observed in one patient	[171]

-: no accurate datum

Declarations

Author contributions

FX: Conceptualization, Writing—original draft, Visualization, Writing—review & editing, Funding acquisition. YX: Writing—original draft, Visualization, Writing—review & editing. YL: Writing—original draft, Visualization.

Conflicts of interest

The authors declare no conflicts of interest.

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Consent to publication

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Availability of data and materials

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Funding

This work was supported by Guangzhou Science and Technology Program Synergistic Innovation Major Project [No.: 201604020146] to FX. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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