Introduction: Interferons (IFNs) modulate the response of the immune system to viruses and decrease vascular leakage. IFNs have shown in-vitro activity against severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). It may improve acute respiratory distress syndrome (ARDS) complications in COVID-19. It is currently under investigation as a potential treatment for COVID-19. Objective: This review assessed the efficacy and safety of interferon and interferon combination therapy in patients with COVID-19. Methods: A systematic review and meta-analysis were performed. A search was conducted from December 1, 2019, until March 30, 2021, in MEDLINE, Cochrane CENTRAL, clinicaltrials.gov, medRxiv, ChinaXiv, and bioRxiv databases for studies and preprints. The search was conducted using the keywords “interferon” and “COVID-19” with no restrictions on language. Reference lists of selected articles were also reviewed. Randomized controlled trials on the use of interferon or interferon combination therapy compared with standard of care were included. Two reviewers independently screened, appraised, and extracted data. The risk of bias was appraised using the Evaluation of Articles on Therapy. Certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Data were analyzed using RevMan 5.4. Results: Three RCTs with low certainty of evidence involving 4,279 hospitalized COVID 19 adult patients were included. IFN-β with or without lopinavir did not significantly reduce mortality (RR 1.12, 95% CI 0.83-1.51 and RR 1.16, 95% CI 0.96-1.39, respectively) compared with standard of care. IFN-β showed clinical response on day 14 (aOR 4.05 (95% CI, 1.42-11.55) and reduction in mortality (aOR 6.65, 95% 1.67-26.45) after adjustment for co-administration of glucocorticoid and IVIg. It also showed increased odds of recovery on day 16 (OR 3.19, 95% CI 1.24-8.24), but it did not significantly reduce the odds of developing severe disease or death (OR 0.28, 95% CI 0.07-1.08), intubation, or death (OR 0.42, 95% CI 0.09-1.83) and hospital discharge on day 16 (OR 1.63, 95% CI 0.61-4.35). Serious adverse events in patients receiving IFN-β did not differ from those receiving standard of care. Conclusion IFN-β or combined with lopinavir did not reduce mortality and progression to severe disease when added to standard of care but showed clinical response on day 16. It demonstrated a reduction in mortality in one study with small sample size. Adverse and serious adverse events were not statistically significant between groups. Its efficacy and safety should further be assessed in randomized controlled trials with higher sample sizes, without co-interventions, and during the earlier stages of COVID-19. Current use of interferon is limited only in clinical trials and compassionate use in severe to critical COVID-19.
Interferons ; COVID-19 ; SARS-CoV-2 ; Antiviral Agents

Objective: This rapid review aimed to summarize data on the accuracy, benefits, harms, and cost-effectiveness of preoperative COVID-19 clinical risk assessment for asymptomatic individuals. Methods: A comprehensive search in MEDLINE, Cochrane CENTRAL, ChinaXiv, medRxiv, and bioRxiv was done until March 10, 2021, using the keywords “COVID-19”, “surgery”, “RT-PCR”, “clinical risk assessment” and “cost-effectiveness”. We searched for studies that assessed the diagnostic accuracy of preoperative clinical risk assessment in COVID-19 screening among asymptomatic individuals, its cost-effectiveness, and its impact on surgical outcomes and management decisions. Risk of bias was assessed using Evaluation of Articles on Diagnosis (Painless Evidence Based Medicine)10 for accuracy studies, Newcastle-Ottawa Scale11 for cohort studies, and Drummond’s checklist12 for economic evaluations. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the overall evidence. Data from included studies were collated qualitatively using summary tables and analyzed in Review Manager 5.4. Pooling of sensitivity and specificity, odds ratio or adjusted odds ratio, and cost-effectiveness measures using a random-effects model was planned. Heterogeneity was determined using I2. Subgroup and sensitivity analyses were preplanned in case significant heterogeneity was found. Results: Three observational studies were included. Preoperative clinical risk assessment for COVID-19 demonstrated a sensitivity of 0.42 (95% CI 0.15-0.72) and a specificity of 0.85 (95% CI 0.76-0.92), using RT-PCR as a reference standard. Indirect evidence showed that any positive clinical risk assessment, COVID-19 antigen or RT-PCR test is done within 0–7 weeks from surgery was associated with a higher 30-day postoperative mortality (RR 3.96, 95% CI 3.41, 4.59) and pulmonary complications (RR 3.41, 95% CI 3.04, 3.83). Delaying surgery at least seven weeks from COVID-19 diagnosis was associated with lower post-surgical complications. Universal pre-endoscopy virus testing using the antigen rapid diagnostic test (Ag-RDT) (ICER = -26,286 €), standard RT-PCR (ICER = -11,128€), or rapid PCR (ICER = -13,703 €) combined with high-risk personal protective equipment (PPE) use in all patients irrespective of test results were found to be more cost-effective compared to no pre-endoscopy testing and no high-risk PPE use, at an, assumed COVID-19 prevalence of 1% or higher among asymptomatic individuals. Overall certainty of evidence was very low. Conclusion Preoperative clinical risk assessment has poor sensitivity but high specificity for detecting COVID-19 among asymptomatic individuals undergoing elective surgery. Objective diagnostic tests such as RT-PCR or Ag-RDT may still be needed to inform surgery schedules.
COVID-19 ; Mass Screening