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COVID 19 hospitalized meta-analysis

RCT-TCZ-COVID-19, 2021
 
NCT04346355
RCTtocilizumab standard of careCOVID 19 hospitalizedsome concern
60/66 inconclusive
    RECOVERY (plasma), 2021
     
    NCT04381936
    RCTconvalescent plasma treatmentcontrolCOVID 19 hospitalizedNA
    -/- inconclusive
      ACTIV-3/TICO LY-CoV555 , 2020
       
      NCT04501978
      RCTneutralizing antibodyplaceboCOVID 19 hospitalizedlow
      163/151 inconclusive
      • inconclusive 6 % increase in time to recovery (PE) with a high degree of certainty due to low risk of bias
      ACTT-2 (Kalil), 2020
       
      NCT04401579
      RCTbaricitinib plus remdesivirremdesivirCOVID 19 hospitalizedlow
      515/518 conclusif
      • demonstrated 16 % increase in clinical improvement,time to recovery (PE) with a high degree of certainty due to low risk of bias
      • suggested 31 % decrease in death or ventilation with a high degree of certainty due to low risk of bias
      Balcells, 2020
       
      NCT04375098
      RCTconvalescent plasma treatmentstandard of careCOVID 19 hospitalizedlow
      28/30 inconclusive
      • inconclusive 33 % decrease in death or ventilation (PE) with a high degree of certainty due to low risk of bias
      ConPlas-19, 2020
       
      NCT04345523
      RCTconvalescent plasma treatmentstandard of careCOVID 19 hospitalizedsome concern
      38/43 inconclusive
        Entrenas (Pilot Calcifediol), 2020
         
        NCT04366908
        RCTVitamin Dstandard of careCOVID 19 hospitalizedsome concern
        50/26 conclusif
        • inconclusive 88 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
        • demonstrated 97 % decrease in ICU admission (PE) with a moderate degree of certainty due to some concern in risk of bias
        Gharbharan et al., 2020
         
        NCT04342182
        RCTconvalescent plasma treatmentstandard of careCOVID 19 hospitalizedsome concern
        43/43 inconclusive
        • inconclusive 5 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
        GLUCOCOVID, 2020 RCTcorticosteroidscontrolCOVID 19 hospitalizedhigh
        34/29 suggested
        • suggested 45 % decrease in clinical deterioration but with a low degree of certainty due to high risk of bias
        Metcovid, 2020
         
        NCT04343729
        RCTmethylprednisoloneplaceboCOVID 19 hospitalizedsome concern
        209/207 inconclusive
        • inconclusive 8 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
        RECOVERY dexamethasone, 2020
         
        NCT04381936
        RCTdexamethasonestandard of careCOVID 19 hospitalizedsome concern
        2104/4321 conclusif
        • demonstrated 17 % decrease in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
        • suggested 10 % increase in hospital discharge with a moderate degree of certainty due to some concern in risk of bias
        in an exploratory subgroup analysis there was no benefit among patients who did not require oxygen (1.22 [0.86 to 1.75]; p=0.14)
        SOLIDARITY (interferon), 2020
         
        NCT04315948
        RCTinterferoncontrolCOVID 19 hospitalizedsome concern
        2063/2064 inconclusive
        • inconclusive 16 % increase in deaths (PE) with a moderate degree of certainty due to some concern in risk of bias
        Synairgen SG016, 2020
         
        NCT04385095
        RCTSNG001 inhaled interferon betaplaceboCOVID 19 hospitalizedhigh
        50/51 suggested
        • suggested 1.3-fold increase in clinical improvement but with a low degree of certainty due to high risk of bias
        Bruce, 2020 OBSnon-steroidal anti-inflammatory drugscontrolCOVID 19 hospitalizedNA
        54/1168 inconclusive
        • inconclusive 11 % decrease in deaths (time to event analysis only) (PE)
        Wenxin, 2020
         
        ChiCTR2000031630.
        OBSCelecoxibcontrolCOVID 19 hospitalizedNA
        36/7 suggested
        • suggested 92 % decrease in clinical deterioration
        • suggested 11.8-fold increase in clinical improvement
        concentrations of PGE2 in urine samples of COVID-19 patients were significantly higher than that of healthy individuals (mean value is 170 ng/ml vs 18.8 ng/ml, p<0.01) and positively correlated with the progression of COVID-19.
        Abolghasemi, 2020
         
        IRCT20200325046860N1
        OBSconvalescent plasma treatmentcontrolCOVID 19 hospitalizedcritical
        115/74 inconclusive
          Annweiler (GERIA-COVID; regular intake of bolus vitamin D), 2020 OBSVitamin DcontrolCOVID 19 hospitalizedNA
          29/32 suggested
          • suggested 93 % decrease in deaths (PE)
          • suggested 92 % decrease in death or ventilation
          Annweiler (GERIA-COVID; Vitamin D Supplementation After COVID-19 Diagnosis), 2020 OBSVitamin DcontrolCOVID 19 hospitalizedNA
          16/32 inconclusive
            Colaneri, 2020 OBStocilizumab controlCOVID 19 hospitalizedcritical
            21/21 inconclusive
              Fernández Cruz, 2020 OBScorticosteroidsstandard of careCOVID 19 hospitalizedserious
              396/67 suggested
              • suggested 66 % decrease in deaths but with a low degree of certainty due to high risk of bias
              HNF Hospital Tocilizumab multidisciplinary team, 2020 OBStocilizumab controlCOVID 19 hospitalizedcritical
              20/25 suggested
              • suggested 87 % decrease in death or transfer to ICU but with a very low degree of certainty due to critical risk of bias
              Malgorzata, 2020 OBSanti-inflammatory therapiescontrolCOVID 19 hospitalizedcritical
              130/66 suggested
              • suggested 59 % decrease in deaths but with a very low degree of certainty due to critical risk of bias
              Martinez-Sanz, 2020 OBStocilizumab controlCOVID 19 hospitalizedcritical
              260/969 suggested
              • suggested 66 % decrease in deaths but with a very low degree of certainty due to critical risk of bias
              Tsai, 2020 OBStocilizumab controlCOVID 19 hospitalizedserious
              66/66 inconclusive
                Jeong, 2020 OBSnon-steroidal anti-inflammatory drugscontrolCOVID 19 hospitalizedNA
                354/1470 safety concern
                • statistically significant 65 % increase in clinical deterioration (PE)
                • statistically significant 87 % increase in cardiovascular or renal events

                COVID 19 all comers meta-analysis

                sarilumab phase 2 high dose unpublished
                 
                NCT04315298
                RCTsarilumab high dose (400mg)placeboCOVID 19 all comershigh
                145/77 suggested
                • suggested 61 % decrease in death or ventilation but with a low degree of certainty due to high risk of bias
                • suggested 73 % decrease in ventilation but with a low degree of certainty due to high risk of bias
                there were negative trends for most outcomes in the “severe” group, while there were positive trends for all outcomes in the “critical” group
                sarimulab phase 2 low dose unpublished
                 
                NCT04315298
                RCTsarilumab low dose (200mg)placeboCOVID 19 all comershigh
                136/77 suggested
                • suggested 72 % decrease in ventilation but with a low degree of certainty due to high risk of bias
                there were negative trends for most outcomes in the “severe” group, while there were positive trends for all outcomes in the “critical” group
                Cai -FAVIPIRAVIR, 2020
                 
                ChiCTR2000029600
                NRainterferonlopinavir/ritonavirCOVID 19 all comersNA
                35/45 suggested
                • suggested 5.5-fold increase in clinical improvement,clinical improvement (14-day)
                Cai -FAVIPIRAVIR, 2020
                 
                ChiCTR2000029600
                NRainterferoninterferonCOVID 19 all comersNA
                35/45 suggested
                • suggested 5.5-fold increase in clinical improvement,clinical improvement (14-day)

                COVID-19 mild to moderate meta-analysis

                CORIMUNO-19, 2020
                 
                NCT04331808
                RCTtocilizumab standard of careCOVID-19 mild to moderatesome concern
                64/67 inconclusive
                  EMPACTA, 2020
                   
                  NCT04372186
                  RCTtocilizumab placeboCOVID-19 mild to moderatesome concern
                  259/129 conclusif
                  • demonstrated 44 % decrease in death or ventilation (PE) with a moderate degree of certainty due to some concern in risk of bias
                  • suggested 45 % decrease in clinical deterioration with a moderate degree of certainty due to some concern in risk of bias
                  Fu, 2020
                   
                  ChiCTR2000030262
                  RCTinterferon / TFF2standard of careCOVID-19 mild to moderatesome concern
                  40/40 no results
                    Idelsis, 2020
                     
                    RPCEC00000307
                    RCTinterferoninterferonCOVID-19 mild to moderatehigh
                    30/33 conclusif
                    • demonstrated 2.3-fold increase in PCR-negative conversion (time to event analysis only) (PE) but with a low degree of certainty due to high risk of bias
                    Khamis, 2020 RCTinterferonstandard of careCOVID-19 mild to moderatesome concern
                    44/45 inconclusive
                      Libster, 2020
                       
                      NCT04479163
                      RCTconvalescent plasma treatmentplaceboCOVID-19 mild to moderatelow
                      80/80 conclusif
                      • demonstrated 48 % decrease in clinical deterioration (PE) with a high degree of certainty due to low risk of bias
                      PLACID, 2020
                       
                      CTRI/2020/04/024775
                      RCTconvalescent plasma treatmentstandard of careCOVID-19 mild to moderatehigh
                      235/229 suggested
                      • inconclusive 7 % increase in death or transfer to ICU (PE) but with a low degree of certainty due to high risk of bias
                      • suggested 20 % increase in PCR-negative conversion (7-day) but with a low degree of certainty due to high risk of bias
                      Rastogi, 2020
                       
                      NCT04459247
                      RCTVitamin DplaceboCOVID-19 mild to moderateNA
                      16/24 suggested
                      • suggested 5.3-fold increase in PCR-negative conversion (PE)
                      Capra, 2020 OBStocilizumab controlCOVID-19 mild to moderatecritical
                      62/23 suggested
                      • suggested 96 % decrease in deaths,deaths (time to event analysis only) but with a very low degree of certainty due to critical risk of bias
                      Espitia-Hernandez, 2020 NRaVitamin Dstandard of careCOVID 19 outpatients, COVID-19 mild to moderateNA
                      28/7 suggested
                      • suggested 714.0-fold increase in PCR-negative conversion

                      COVID-19 severe or critically meta-analysis

                      REMAP-CAP sarilumab, 2021
                       
                      NCT02735707
                      RCTsarilumabstandard of careCOVID-19 severe or criticallysome concern
                      48/402 conclusif
                      • demonstrated 76 % increase in clinical improvement (PE) with a moderate degree of certainty due to some concern in risk of bias
                      REMAP-CAP tocilizumab, 2021
                       
                      NCT02735707
                      RCTtocilizumab standard of careCOVID-19 severe or criticallysome concern
                      353/402 conclusif
                      • suggested 30 % decrease in deaths with a moderate degree of certainty due to some concern in risk of bias
                      • demonstrated 64 % increase in clinical improvement (PE) with a moderate degree of certainty due to some concern in risk of bias
                      AlQahtani, 2020
                       
                      NCT04356534
                      RCTconvalescent plasma treatmentstandard of careCOVID-19 severe or criticallysome concern
                      20/20 inconclusive
                      • inconclusive 33 % decrease in ventilation (PE) with a moderate degree of certainty due to some concern in risk of bias
                      BACC Bay Tocilizumab Trial, 2020
                       
                      NCT04356937
                      RCTtocilizumab placeboCOVID-19 severe or criticallylow
                      161/81 inconclusive
                      • inconclusive 17 % decrease in death or ventilation (PE) with a high degree of certainty due to low risk of bias
                      Bajpai M, 2020
                       
                      NCT04346446
                      RCTconvalescent plasma treatmentcontrolCOVID-19 severe or criticallyhigh
                      14/15 inconclusive
                      • inconclusive 74 % decrease in off oxygenation (PE) but with a low degree of certainty due to high risk of bias
                      CAPE-COVID, 2020
                       
                      NCT02517489
                      RCTHydrocortisoneplaceboCOVID-19 severe or criticallylow
                      76/73 inconclusive
                      • inconclusive 29 % decrease in death or ventilation (PE) with a high degree of certainty due to low risk of bias
                      COALITION II (Furtado), 2020
                       
                      NCT04321278
                      RCTHydrocortisonehydroxychloroquineCOVID-19 severe or criticallysome concern
                      214/183 inconclusive
                        CODEX (Tomazini), 2020
                         
                        NCT04327401
                        RCTdexamethasonestandard of careCOVID-19 severe or criticallysome concern
                        151/148 inconclusive
                          COVACTA (Rosas), 2020
                           
                          NCT04320615
                          RCTtocilizumab placeboCOVID-19 severe or criticallysome concern
                          294/144 inconclusive
                            Davoudi-Monfared, 2020
                             
                            IRCT20100228003449N2
                            RCTinterferonstandard of careCOVID-19 severe or criticallyhigh
                            46/46 no results
                              Edalatifard, 2020
                               
                              IRCT20200404046947N1
                              RCTmethylprednisolonestandard of careCOVID-19 severe or criticallyhigh
                              34/34 conclusif
                              • demonstrated 71 % decrease in deaths (PE) but with a low degree of certainty due to high risk of bias
                              Murai, 2020
                               
                              NCT04449718
                              RCTVitamin DplaceboCOVID-19 severe or criticallysome concern
                              120/120 inconclusive
                                PlasmAr, 2020
                                 
                                NCT04344535
                                RCTconvalescent plasma treatmentplaceboCOVID-19 severe or criticallylow
                                228/105 inconclusive
                                • inconclusive 19 % decrease in clinical improvement (PE) with a high degree of certainty due to low risk of bias
                                PlasmAr, 2020
                                 
                                NCT04344535
                                RCTconvalescent plasma treatmentcontrolCOVID-19 severe or criticallylow
                                228/105 inconclusive
                                • inconclusive 19 % decrease in clinical improvement (PE) with a high degree of certainty due to low risk of bias
                                REMAP-CAP, fixed 7-day course, 2020
                                 
                                NCT02735707
                                RCTHydrocortisonestandard of careCOVID-19 severe or criticallysome concern
                                143/108 inconclusive
                                  REMAP-CAP, shock-dependent course, 2020
                                   
                                  NCT02735707
                                  RCTcorticosteroidsstandard of careCOVID-19 severe or criticallysome concern
                                  152/108 inconclusive
                                    Yekaninejad, 2020
                                     
                                    IRCT20100228003449N2
                                    RCTinterferonstandard of careCOVID-19 severe or criticallysome concern
                                    33/33 conclusif
                                    • demonstrated 2.4-fold increase in clinical improvement (time to event analysis only) (PE) with a moderate degree of certainty due to some concern in risk of bias
                                    Li, 2015
                                     
                                    ChiCTR2000029757
                                    RCTconvalescent plasma treatmentstandard of careCOVID-19 severe or criticallysome concern
                                    52/51 inconclusive
                                    • inconclusive 40 % increase in clinical improvement (PE) with a moderate degree of certainty due to some concern in risk of bias
                                    Ana-COVID (Huet), 2020 OBSanakinracontrolCOVID-19 severe or criticallyserious
                                    52/44 suggested
                                    • suggested 78 % decrease in clinical deterioration,death or transfer to ICU but with a low degree of certainty due to high risk of bias
                                    Andrew, 2020 OBStocilizumab controlCOVID-19 severe or criticallyNA
                                    198/413 inconclusive
                                      ARI-RAF (Della-Torre), 2020 OBSsarilumabcontrolCOVID-19 severe or criticallyNA
                                      28/28 inconclusive
                                        Biran, 2020 OBStocilizumab controlCOVID-19 severe or criticallyserious
                                        210/420 suggested
                                        • suggested 36 % decrease in deaths but with a low degree of certainty due to high risk of bias
                                        Duan, 2020 OBSconvalescent plasma treatmentcontrolCOVID-19 severe or criticallycritical
                                        10/10 inconclusive
                                          Hegerova, 2020 OBSconvalescent plasma treatmentcontrolCOVID-19 severe or criticallycritical
                                          20/20 inconclusive
                                            Jianfeng, 2020 OBScorticosteroidsstandard of careCOVID-19 severe or criticallyserious
                                            -/- safety concern
                                            • statistically significant 1.8-fold increase in deaths,deaths (time to event analysis only) but with a low degree of certainty due to high risk of bias
                                            • statistically significant 2.0-fold increase in deaths,deaths (time to event analysis only) but with a low degree of certainty due to high risk of bias
                                            Mathilde, 2020 OBStocilizumab controlCOVID-19 severe or criticallycritical
                                            30/29 suggested
                                            • suggested 75 % decrease in deaths but with a very low degree of certainty due to critical risk of bias
                                            Raef, 2020 OBScorticosteroidsstandard of careCOVID-19 severe or criticallycritical
                                            -/- suggested
                                            • suggested 55 % decrease in deaths but with a very low degree of certainty due to critical risk of bias
                                            Rasheed, 2020 OBSconvalescent plasma treatmentcontrolCOVID-19 severe or criticallycritical
                                            21/28 inconclusive
                                              Rojas-Marte, 2020 OBStocilizumab controlCOVID-19 severe or criticallycritical
                                              96/97 inconclusive
                                                Sean, 2020 OBSconvalescent plasma treatmentcontrolCOVID-19 severe or criticallycritical
                                                39/156 inconclusive
                                                  Somers, 2020 OBStocilizumab controlCOVID-19 severe or criticallycritical
                                                  78/76 safety concern
                                                  • suggested 45 % decrease in deaths,deaths (time to event analysis only) but with a very low degree of certainty due to critical risk of bias
                                                  • statistically significant 2.3-fold increase in superinfection but with a very low degree of certainty due to critical risk of bias
                                                  TOCI-RAF Study Group (Campochiaro), 2020 OBStocilizumab controlCOVID-19 severe or criticallyNA
                                                  32/33 inconclusive
                                                    Lu, 2020 OBScorticosteroidscontrolCOVID-19 severe or criticallyserious
                                                    151/93 inconclusive
                                                      Joyner, 2020
                                                       
                                                      NCT04338360
                                                      NRaconvalescent plasma treatmentconvalescent plasma treatmentCOVID-19 severe or criticallyserious
                                                      515/561 inconclusive

                                                        PE: primary endpoint; (a): to be demonstrated a result must be statistically significant on a primary endpoint (with multiplicity adjustment if necessary);
                                                        Study risk of bias assessed for the study primary endpoint(s) or the main endpoints in case of no formally defined primary endpoint(s).