Table 5.
Effect and safety of immunomodulatory drugs assessed in mild COVID-19 (without oxygen support)
| Outcome | Drug | Author, year (ref) | Study design | Study groups | Results | Risk of bias |
| Mortality | Hydroxychloroquine | Lyngbakken et al 202078 | RCT | SOC+HCQ SOC |
No difference between groups. | High |
| Ulrich et al 202021 | RCT | SOC+HCQ SOC |
No difference between groups at day 14 for the composite criteria (death, ICU admission, mechanical ventilation, extracorporeal membrane oxygenation and/or vasopressor use). | High | ||
| Baricitinib | Bronte et al 202074 | Prospective | SOC+BARI SOC |
1/20 (5%) in BARI group versus 25/56 (45%) SOC group (p<0.001). | High | |
| IFN alpha | Wang et al 202071 | Prospective | SOC+IFN alpha-2b SOC |
None of the patients died in any group. | High | |
| Discharge/Time to Hospital Discharge | Hydroxychloroquine | Lyngbakken et al 202078 | RCT | SOC+HCQ SOC |
No difference between groups p by log-rank test=0.71. | High |
| Baricitinib | Cantini et al 202073 | Prospective | SOC+BARI SOC |
Discharge at week 2 occurred in 58% (7/12) of the BARI-treated patients versus 8% (1/12) of controls (p=0.027). | High | |
| Leflunomide | Wang et al 202069 | RCT | SOC+LEF SOC |
No difference between groups 29.0 (IQR 19.3–47.3) days versu 33.0 (IQR 29.3–42.8) days p=0.170. | High | |
| IFN alpha | Wang et al 202071 | Prospective | SOC+IFN alpha-2b SOC |
Shorter time to discharge in the treatment group. Even shorter if early intervention. | High | |
| Negative conversion of SARS-CoV-2 | Hydroxychloroquine | Mitja et al 202066 | RCT | SOC+HCQ SOC | No difference across groups day 3 and day 7. | Unclear |
| Chen et al 202017 | RCT | SOC+HCQ SOC | No difference in time to negative PCR at day 14: 5 days (95% CI 1 to 9 days) and 10 days (95% CI 2 to 12 days) for the HCQ and SOC groups, respectively (p=0.40). | High | ||
| Omrani et al 202068 | RCT | SOC+HCQ SOC | No difference across groups day 6 negative PCR (p=0.821) HCQ+AZT 16/152 (10.5%), HC 19/149 (12.8%), placebo 18/147 (12.2%). Day 14 (p=0.072) HC +AZ 30/149 (20.1%), HC 42/146 (28.8%), placebo 45/143 (31.5%). |
High | ||
| Leflunomide | Hu et al 202070 | RCT | SOC+LEF SOC |
5 days LEF versus 11 days control group (p=0.046). | High | |
| Wang et al 202069 | RCT | SOC+LEF SOC |
No difference between groups HR for negative RT-PCR, 0.70; (95% CI 0.391 to 1.256; p=0.186). |
High | ||
| IFN alpha | Wang et al 202071 | Prospective | SOC+IFN alpha-2b SOC |
Faster in the treatment group. | High | |
| IFN kappa | Fu et al 202072 | RCT | SOC+IFN kappa SOC | Significantly shorter time to viral RNA negative conversion in IFN group. | Unclear | |
| Treatment emergent AEs | Hydroxychloroquine | Mitjà et al 202066 | RCT | SOC+HCQ SOC |
AE in SOC 16/184 (8.7%)<121/169 (72.0%) in HCQ group. | Unclear |
| Skipper et al 202067 | RCT | SOC+HCQ SOC |
AEs with HCQ >PBO at day 5 (43% (92 of 212) versus 22% (46 of 211); p<0.001). GI symptoms in 31% (66 of 212). | Unclear | ||
| Chen et al 202017 | RCT | SOC+HCQ SOC |
No SAE reported. Grades 1 and 2 HCQ-related adverse events included headache (21.1%), dizziness (5.3%), gastritis (5.3%), diarrhoea (5.3%), nausea (5.3%) and photophobia (5.3%). | High | ||
| Omrani et al 202068 | RCT | SOC+HCQ SOC |
No SAE. No association (p=0.708) between study group and development of pneumonia, which was diagnosed in seven participants (1.5%): three (2.0%) in the HC+AZ group, one (0.7%) in the HC group and three (2.0%) in the placebo group. | High | ||
| Ulrich et al 202021 | RCT | SOC+HCQ SOC |
No difference in AEs between the groups. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer and a trend towards an increased length of stay. | High | ||
| Leflunomide | Hu et al 202070 | RCT | SOC+LEF SOC |
ALT and AST reversibly increased LEF group (p=0.049 and p=0.176, respectively). | High | |
| Wang et al 202069 | RCT | SOC+LEF SOC |
No difference in AEs between the groups. | High | ||
| Tocilizumab | Zhao et al 202075 | RCT | SOC+favipiravir SOC+favipiravir +TCZ |
Nine adverse reactions were reported in the combined treatment group, and two adverse reactions were reported in the favipiravir group and the TCZ group, respectively. | High | |
| Baricitinib | Cantini et al 202073 | Prospective | SOC+BARI SOC |
No SAEs. 1 patient with transaminases elevation in the BARI group. | High | |
| Bronte et al 202074 | Prospective | SOC+BARI SOC |
No SAEs. | High | ||
| IFN alpha | Wang et al 202071 | Prospective | SOC+IFN alpha-2b SOC |
No difference in AEs between the groups. | High | |
| IFN kappa | Fu et al 202072 | RCT | SOC+IFN kappa SOC | No SAEs. | Unclear |
Only studies reporting on the corresponding outcome are shown.
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AZT, azithromycin; BARI, baricitinib; COL, colchicine; DEX, dexamethasone; GI, gastrointestinal; HCQ, hydroxychloroquine; HCT, hydrocortisone; IFN, interferon; LEF, leflunomide; MTP, methylprednisolone; PBO, placebo; RT-PCR, real time PCR; RUXO, ruxolitinib; SAE, severe adverse event; SAEs, serious adverse events; SE, standard error; SOC, standard of care; TCZ, tocilizumab.