meta|Evidence - COVID-19
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high-dose IFN beta-1a (n=83) vs. IFN beta-1a (n=85)
randomized controlled trial some concerns about risk of bias
High-dose IFN-β 1a
IFN-β 1a (Recigen) subcutaneous injections of 88μg (24,000 IU) on days 1, 3, 6 plus lopinavir/ritonavir (Kaletra) 400mg/100 mg twice a day for 10 days, orally.
Low-dose IFN-β 1a
IFN-β 1a (Recigen) subcutaneous injections of 44μg (12,000 IU) on days 1, 3, 6 lopinavir/ritonavir (Kaletra) 400mg/100 mg twice a day for 10 days, orally.
Intervention and control groups received standards ofcare including necessary oxygen support and non-invasive or invasive mechanical ventilation.
COVID 19 hospitalized
Age >=18 years, oxygen saturation (SPO2) =< 93% or respiratory rate>= 24,presence of at least one of following manifestations on admission: Cough, shortness of breath,nasal congestion/ discharge, myalgia/arthralgia, radiation contactless body temperature >=37.8,diarrhea/vomiting and headache or fatigue. The patients’ symptoms must be in acute phase (=< 14 days).
Open-label
Single center, Loghman Hakim hospital.
The utilized seven-step ordinal scale consists of the subsequent categories: (I) Not hospitalized, and has no activity limitations; (II) Not hospitalized, but has activity limitations; (III) Hospitalized, but does not need any supplemental oxygen; (IV) Hospitalized, and needs supplemental oxygen; (V) Hospitalized, and needs either High-Flow Nasal Cannula (HFNC) or non-invasive ventilation;(VI) Hospitalized, and needs invasive ventilation; and (VII) Dead.
IFN beta-1a (n=2063) vs. control (n=2064)
randomized controlled trial some concerns about risk of bias
Interferon-ß1a
Interferon (mainly subcutaneous): Three doses over six days of 44µg subcutaneous Interferon-ß1a; where intravenous interferon was available, patients on high-flow oxygen, ventilators or ECMO were instead to be given 10µg intravenously once daily for six days
Control
Lopinavir or local standard of care
Five arms: hydroxychloroquine, interferon, remdesivir, lopinavir, or standard of care only. All patients were to receive the local standard of care.
COVID 19 hospitalized
Consenting adults (age ≥18) hospitalised with definite COVID-19, not already receiving any of the study drugs, without known allergy or contra-indications to any of them (in the view of the physician responsible for their care), and without anticipated transfer within 72 hours to a non-study hospital.
Open label.
Multicenter, 405 hospitals in 30 countries in all six WHO regions.
2,063 patients in the study group = 651 patients treated with Interferon plus Lopinavir and 1,412 patients treated with Interferon only. 2,064 control patients = 679 Lopinavir and 1,385 Local SoC.
IFN gamma (n=41) vs. standard of care (n=38)
randomized controlled trial high risk of bias
IFN alpha-2b plus IFN gamma (HeberFERON)
Subcutaneous treatment with a co-lyophilized combination of 3.0 MIU IFN-α2b and 0.5 MIU IFN-γ (HeberFERON, CIGB, Havana, Cuba), twice a week for two weeks,
IFN alpha-2b alone (Heberon)
Intramuscular injection of 3.0 MIU IFN-α2b (Heberon® Alpha R, CIGB, Havana, Cuba), thrice a week.
Additionally, all patients received lopinavir-ritonavir 200/50 mg every 12 h and chloroquine 250 mg every 12 h (standard of care).
COVID 19 hospitalized
Adult (≥19 years-old) patients with RT-PCR confirmed SARS-CoV-2, ECOG functional status ≥ 2 (Karnofsky ≥ 70%), and voluntariness by signing the informed consent.
Open-label
Single center, Military Central Hospital “Luis Diaz Soto”, Havana, Cuba.
Phase 2.
recombinant super-compound interferon rSIFN-co (n=48) vs. IFN alpha (n=48)
randomized controlled trial some concerns about risk of bias
Nebulized rSIFN-co
12 IU, twice daily immediately after randomization until discharged from the hospital, but not more than 28 days.
Nebulized interferon-alpha
Interferon-alpha-2a or interferon-alpha-2b, 5 million IU, twice daily, immediately after randomization until discharged from thehospital, but not more than 28 days.
All patients received the standard care. The baseline antiviral agents were lopinavir-ritonavir (400mg and100 mg, orally, twice daily) or umifenovir (200 mg,orally, thrice daily).
COVID 19 hospitalized
1. Age over 18 years old; 2. Real-time fluorescent RT-PCR for respiratory or blood specimens to detect novel coronavirus nucleic acid positive; 3. The sequence of virus genes in respiratory or blood samples was highly homologous with the known novel coronavirus; 4. A common or severe type of new type of coronavirus pneumonia was diagnosed. The common patients diagnosed with novel coronavirus pneumonia that have fever, respiratory symptoms, and imaging shows pneumonia. Some severe patients could be included. Accord with any of the following: (1) Respiratory distress, RR >= 30 times / minute; (2) In resting state, means oxygen saturation <= 93%; (3) Arterial blood oxygen partial pressure (PaO2) / oxygen concentration (FiO2) <=300mmHg.
Single-blind.
Multicenter, five hospitals in Wuhan city and Chengdu city, China.
Patients were blinded to treatment allocation, whereas treating physicians were aware of group allocations.
This trial was designed as an exploratory one and was not powered statistically to measure a specific outcome,thus sample size estimates were not based on statistical power assessments.
SNG001 inhaled interferon beta (n=309) vs. placebo (n=314)
randomized controlled trial risk of bias NA
SNG001
in addition to standard of care
placebo
COVID 19 hospitalized
double-blind
SNG001 inhaled interferon beta (n=50) vs. placebo (n=51)
randomized controlled trial some concerns about risk of bias
Interferon beta-1a (SNG001)
6 MIU interferon beta-1a (SNG001) for inhalation use via nebuliser, once daily for 14 days.
Placebo
Nebulisation solution for inhalation use, once daily for 14 days. Placebo had the same formulation as SNG001, excluding the active substance.
Local standard of care treatment in both groups. SNG001 and placebo were identical in appearance.
COVID 19 hospitalized
Adults aged 18 years or older, admitted to hospital with COVID-19 symptoms. Patients had to have a confirmed SARS-CoV-2test result in a UK National Health Service (NHS) diagnostic, qualitative RT-PCR assay or a positive point-of-care test (FebriDx, Lumos Diagnostics, Sarasota, FL,USA) within the previous 24 h.17 Patients unable to use a nebuliser with a mouthpiece (eg, ventilated patients and patients in intensive care); were ecluded.
Double-blind.
Multicentre, 9 specialist hospitals in United Kingdom.
Phase II pilot trial.The OSCI is a 9-point scale, where 0 corresponds to no infection and 8 corresponds to death.
interferon / TFF2 (n=40) vs. standard of care (n=40)
randomized controlled trial some concerns about risk of bias
Interferon kappa plus TFF2
Both proteins (5 mg TFF2 plus 2 mg IFN-k) were dissolved in 5 mL sterilized water, and the combination aerosol was delivered to the patient for 20 to 30 min by a nasal mask driven by a medical compressed air atomizer (YUWELL, 403M). The aerosol inhalation treatment started from the first day of hospitalization and was administered 6 times every 24 h.
Standard care
Standard care alone. Standard care included symptomatic treatment with hydroxychloroquine, antibiotic agents, vasopressors, antifever medicine, vitamin C, immune enhancers, or traditional Chinese medicines.
Both groups received standard of care.
COVID-19 mild to moderate
Male and nonpregnant femalepatients at 18 years of age or older were eligible after they were confirmedas SARS-CoV-2 positive by RT-PCR. In addition, patients wereincluded if their peripheral capillary oxygen saturation (SpO2) was >94% on room air at screening. Symptoms of infection include fever,cough, and myalgia, with diarrhea, with the subsequent developmentof dyspnea or of pneumonia on chest CT. Patients with moderatepneumonia were then included following Diagnosis and TreatmentProtocol for Novel Coronavirus Pneumonia
Open-label.
Single center, Shanghai Public Health Clinical Center, Shanghai, China.
peginterferon (n=60) vs. placebo (n=60)
randomized controlled trial some concerns about risk of bias
Peginterferon Lambda-1a
Peginterferon Lambda-1a (180 mcg subcutaneous injection) single dose alone with standard of care.
Placebo
Normal saline placebo subcutaneous injection along with standard of care Treatment for COVID-19 Infection.
COVID-19 mild to moderate
Age ≥ 18 years and ≤ 75 years at the time of the assessmentAble and willing to understand the study, adhere to all study procedures, and provide written informed consentDiagnosis of COVID-19 disease:If symptomatic, the presence of mild to moderate symptoms without signs of respiratory distress, with FDA-cleared molecular diagnostic assay positive for SARS-CoV-2 within 72 hours from swab to the time of commencing informed consent:If asymptomatic, initial diagnosis of SARS-CoV-2 infection with positive FDA-cleared molecular diagnostic assay obtained no more than 72 hours from initial swab to the time of commencing informed consent
Open-label.
Single-blind.
Phase II. Single-blind study in which only patients are blinded.
pegylated interferon-α2b (n=20) vs. standard of care (n=20)
randomized controlled trial some concerns about risk of bias
Single dose of PEG IFN-α2b
PEG IFN-α2b; 1 mg/kg subcutaneous injection, single dose, plus SOC.
Standard of care
SOC alone.
Antipyretics, cough suppressants, antibiotics, steroids, vitamins, anticoagulants, and hydroxychloroquine were administered as per regulatory recommendation and approval.
COVID-19 mild to moderate
1. Ability to comprehend and willingness to sign a written ICF for the study 2. Male or non-pregnant females, >= 18 years of age at the time of enrolment 3. Understands and agrees to comply with planned study procedures 4. Agrees to the collection of pharyngeal swabs and blood sample as per protocol 5. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen 6.Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study (acceptable methods will be determined by the site).
Open-label.
Multicenter, six study centers in India.
The primary efficacy endpoint was clinical status assessed onday 15 on a WHO 7-point ordinal scale consisting of the following categories: 1, not hospitalized, no limitations of activities; 2, not hospitalized, limitation on activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, on non-invasive ventilation or high flow oxygen devices; 6, hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 7, death.
Phase II. All patients were hospitalized.
pegylated interferon-α2b (n=120) vs. standard of care (n=130)
randomized controlled trial some concerns about risk of bias
Pegylated interferon-α2b
Standard of care plus a single dose of PEG IFN-α2b.
Standard of care
SOC treatments [i.e. antipyretics, cough suppressants, antibiotics, steroids, vitamins, anticoagulants, hydroxychloroquine and antivirals (e.g. remdesivir)] were administered as per the COVID-19 clinical management guidelines of the Ministry of Health, Government of India and the practices of the individual institutions.
COVID-19 mild to moderate
age ≥18 years, RT-PCR-confirmed SARS-CoV-2 infection, pneumonia with no signs of severe disease, respiratory rate ≥24 breaths/min, SpO2 90–94%, and a negative pregnancy test (for female patients of child-bearing potential).
Open-label.
Multicenter; 20 study centers across India.
The scale consists of the following categories: 1, not hospitalized, no limitation of activities; 2, not hospitalized, limitation of activities; 3, hospitalized, does not require supplemental oxygen; 4, hospitalized, requires supplemental oxygen; 5, hospitalized, requires noninvasive ventilation or on high flow oxygen devices; 6, hospitalized, requires invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 7, death.
IFN beta-1a (n=487) vs. placebo (n=482)
randomized controlled trial some concerns about risk of bias
Interferon beta-1a
44 mcg of interferon beta-1a administered by a 0.5 mL subcutaneous injection on Days 1, 3, 5, and 7 while hospitalized for a total of 4 doses. plus remdesivir.
Placebo
0.5 mL placebo injection administered subcutaneously on Days 1, 3, 5, and 7 while hospitalized for a total of 4 doses plus remdesivir.
All hospitalized patients also received intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days. All patients received standard supportive care by the trial site hospital,including glucocorticoids, but other experimental treatments for COVID-19 were prohibited.
COVID-19 severe or critically
Patients already on mechanical ventilation were excluded.
Double-blind.
63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, USA).
Disease severity was defined according to the eight-category ordinal scale used in previous ACTT studies. Patients defined by a score of :1 were not hospitalised and had no limitations to theiractivities; 2 were not hospitalised but had limitations to their activities or required home oxygen supplementation,or both; 3 were hospitalised but did not require supplemental oxygen and no longer required ongoing medical care; 4 were hospitalised and did not require supplemental oxygen but did require ongoing medical care; 5 were hospitalised and required any supplemental oxygen;6 were hospitalised and required non-invasive ventilation or use of high-flow oxygen devices; 7 were hospitalised and receiving invasive mechanical ventilation or extracorporeal membrane oxygenation; and 8 were those who had died.
IFN beta-1a (n=20) vs. standard of care (n=20)
randomized controlled trial some concerns about risk of bias
IFNβ1a
IFNβ1a (Recigen) (Subcutaneous injections of 44μg (12,000 IU) ondays 1, 3, 6) plus a single dose of hydroxychloroquine 400mg and Lopinavir/Ritonavir 400mg/100 mg twice a day for 10 days.
Standard of care
Hydroxychloroquine (Single dose of 400 mg on day1, orally) and Lopinavir/Ritonavir (Kaletra) (400mg/100 mg twice a day for 10 days) .
Three arms: IFNβ1a, IFNβ1b, control group. All three groups received standards of care consisting of the necessary oxygen support, non-invasive, or invasive mechanical ventilation.
COVID-19 severe or critically
Male, non-lactating, and non-pregnant female patients with at least 18 years of age who had confirmed COVID-19, defined as a positive test of Reverse Transcriptase Polymerase-Chain Reaction (RT-PCR) with peripheral capillary oxygen saturation level (SpO2) ≤ 93% on pulse oximetry OR a respiratory frequency ≥ 24/minute while breathing ambient air] AND at least one in every of the following: contactless infrared forehead thermometer temperature of ≥ 37·8, muscle ache, rhinitis, headache, cough or fatigue onadmission AND acute onset time for the symptoms (Days ≤ 14).
Open-label.
Single center, Loghman Hakim Hospital, a leading academic hospital of Shahid Beheshti ,Tehran, Iran.
Seven-step ordinal scale: (I) Not hospitalized, and has no activity limitations; (II) Not hospitalized, but has activity limitations; (III) Hospitalized, but does not need any supplemental oxygen; (IV) Hospitalized, and needs supplemental oxygen; (V) Hospitalized, and needs either High-Flow Nasal Cannula (HFNC) or non-invasive ventilation;(VI) Hospitalized, and needs invasive ventilation; and (VII) Dead.
IFN beta-1a (n=46) vs. standard of care (n=46)
randomized controlled trial high risk of bias
Interferon beta-1a
IFN β-1a in addition to the standard of care. Each 44 micrograms/ml (12 million IU/ml) of interferon β-1a (ReciGen®, CinnaGen Co., Iran) was subcutaneously injected three times weekly for two consecutive weeks.
Standard of care
Hydroxychloroquine (400 mg BD in first day and then 200 mg BD) plus lopinavir/ritonavir (400/100 mg BD) or atazanavir/ritonavir (300/100 mg daily) for 7-10 days (hospital protocol).
Both groups received standard of care. Primary care, respiratory support, fluid, electrolytes, analgesic, antipyretic, corticosteroid and antibiotic were recommended in the hospital protocol if indicated.
COVID-19 severe or critically
Adult patients (aged ≥ 18 years old) with the severe disease with following criteria: (1) hypoxemia (need for noninvasive or invasive respiratory support to provide capillary oxygen saturation above 90%) (2) Hypotension (systolic blood pressure less than 90 mmHg or vasopressor requirement) (3) renal failure secondary to COVID-19 (according to KDIGO definition) (4) neurologic disorder secondary to COVID-19 (decrease of 2 or more scores in Glasgow Coma Scale) (5) thrombocytopenia secondary to COVID-19 (platelet count less than 150000 /mm3) (6) severe gastrointestinal symptoms secondary to COVID-19 (vomiting/diarrhea that caused at least mild dehydration). The diagnosis of COVID-19 was according to either a positive Real-Time Polymerase Chain Reaction (RT-PCR) of the respiratory tract samples or clinical signs/symptoms and imaging findings highly suspicious for COVID-19.
Open-label.
Single center, Imam Khomeini Hospital Complex, Tehran, Iran.
Clinical response was defined according to the six-category ordinal scale. The six categories are: (1) discharge (2) hospital admission, not requiring oxygen (3) hospital admission, requiring oxygen (4) hospital admission, requiring non-invasive positive pressure ventilation (5) hospital admission requiring invasive mechanical ventilation (6) death.
IFN beta-1b (n=20) vs. standard of care (n=20)
randomized controlled trial some concerns about risk of bias
IFNβ1b
IFNβ1b subcutaneous injections of 8,000,000 IU on days 1, 3, 6 plus a single dose of hydroxychloroquine 400mg on the first day and Lopinavir/Ritonavir 400mg/100 mg twice a day for ten days.
Standard of care.
Hydroxychloroquine: single dose of 400 mg on day1, orally, and Lopinavir/Ritonavir (Kaletra): 400mg/100 mg twice a day for 10 days, orally.
Three arms: IFNβ1a, IFNβ1b, control group. All three groups received standards of care consisting of the necessary oxygen support, non-invasive, or invasive mechanical ventilation.
COVID-19 severe or critically
Male, non-lactating, and non-pregnant female patients with at least 18 years of age who had confirmed COVID-19, defined as a positive test of Reverse Transcriptase Polymerase-Chain Reaction (RT-PCR) with peripheral capillary oxygen saturation level (SpO2) ≤ 93% on pulse oximetry OR a respiratory frequency ≥ 24/minute while breathing ambient air] AND at least one in every of the following: contactless infrared forehead thermometer temperature of ≥ 37·8, muscle ache, rhinitis, headache, cough or fatigue onadmission AND acute onset time for the symptoms (Days ≤ 14).
Open-label.
Single center, Loghman Hakim Hospital, a leading academic hospital of Shahid Beheshti ,Tehran, Iran.
Seven-step ordinal scale: (I) Not hospitalized, and has no activity limitations; (II) Not hospitalized, but has activity limitations; (III) Hospitalized, but does not need any supplemental oxygen; (IV) Hospitalized, and needs supplemental oxygen; (V) Hospitalized, and needs either High-Flow Nasal Cannula (HFNC) or non-invasive ventilation;(VI) Hospitalized, and needs invasive ventilation; and (VII) Dead.
IFN beta-1b (n=40) vs. standard of care (n=40)
randomized controlled trial some concerns about risk of bias
Interferon β-1b.
IFN β-1b (250 mcg subcutaneously every other day for two consecutive weeks) plus national protocol medications.
National protocol medications only.
National protocol medications (lopinavir/ritonavir (400/100 mg BD) or atazanavir/ritonavir (300/100 mg daily) plus hydroxychloroquine (400 mg BD in first day and then 200 mg BD) for 7-10 days).
Both groups received national protocol medications. The national protocol consisted lopinavir/ritonavir (400/100 mg BD) or atazanavir/ritonavir (300/100 mg daily) plus hydroxychloroquine (400 mg BD in first day and then 200 mg BD) for 7–10 days. Other supportive cares such as fluid therapy, stress ulcer prophylaxis, deep vein thrombosis, treatment of electrolyte disorders and antibiotic therapy were considered according to the hospital protocols.
COVID-19 severe or critically
Adult patients (≥18 years old) with positive PCR and clinical symptoms/signs of pneumonia (including dyspnea, cough and fever),peripheral oxygen saturation (SPO2) ≤ 93% in ambient air or arterial oxygen partial pressure to fractional inspired oxygen (PaO2/ FiO2) < 300 or SPO2/FiO2 < 315 and lung involvement in chest imaging.
Open-label.
Single-center, Imam Khomeini Hospital Center in Tehran, Iran.
Clinical improvement was defined as improvement of at least two points from the baseline status on the six-category ordinal scale. This scale contains the subsequent categories: (1) death (2) hospital admission requiring invasive mechanical ventilation (3) hospital admission, requiring non-invasive positive pressure ventilation (4) hospital admission, requiring oxygen (5) hospital admission, not requiring oxygen (6) discharge.
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