OBJECTIVE:

To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19.

DESIGN:

Living systematic review and network meta-analysis.

DATA SOURCES:

World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021.

STUDY SELECTION:

Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.

METHODS:

Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach.

RESULTS:

The first iteration of this living network meta-analysis includes nine randomised trials-six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain.

CONCLUSIONS:

Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection.

SYSTEMATIC REVIEW REGISTRATION:

This review was not registered. The protocol established a priori is included as a supplement.

READERS' NOTE:

This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Ivermectin, an antiparasitic drug, has been repurposed for COVID-19 treatment during the SARS-CoV-2 pandemic. Although its antiviral efficacy was confirmed early in vitro and in preclinical studies, its clinical efficacy remained ambiguous. Our purpose was to assess the efficacy of ivermectin in terms of time to viral clearance based on the meta-analysis of available clinical trials at the closing date of the data search period, one year after the start of the pandemic. This meta-analysis was reported by following the PRISMA guidelines and by using the PICO format for formulating the question. The study protocol was registered on PROSPERO. Embase, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), bioRvix, and medRvix were searched for human studies of patients receiving ivermectin therapy with control groups. No language or publication status restrictions were applied. The search ended on 1/31/2021 exactly one year after WHO declared the public health emergency on novel coronavirus. The meta-analysis of three trials involving 382 patients revealed that the mean time to viral clearance was 5.74 days shorter in case of ivermectin treatment compared to the control groups [WMD = -5.74, 95% CI (-11.1, -0.39), p = 0.036]. Ivermectin has significantly reduced the time to viral clearance in mild to moderate COVID-19 diseases compared to control groups. However, more eligible studies are needed for analysis to increase the quality of evidence of ivermectin use in COVID-19.

ObjectiveTo determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19).

DesignLiving systematic review and network meta-analysis.

Data sourcesWHO covid-19 database, a comprehensive multilingual source of global covid-19 literature to 19 January 2021, and six additional Chinese databases to 20 January 2021.

Study selectionRandomized trials in which people at risk of covid-19 were randomized to drug prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.

MethodsAfter duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.

ResultsThe first iteration of this living network meta-analysis includes nine randomized trials - six addressing hydroxychloroquine (6,059 participants), one addressing ivermectin combined with iota-carrageenan (234 participants) and two addressing ivermectin alone (540 participants), all compared to standard care or placebo. Hydroxychloroquine has no important effect on admission to hospital (risk difference (RD) 1 fewer per 1,000, 95% credible interval (CrI) 3 fewer to 4 more, high certainty) or mortality (RD 1 fewer per 1,000, 95% CrI 2 fewer to 3 more, high certainty). Hydroxychloroquine probably has no important effect on laboratory-confirmed infection (RD 2 more per 1,000, 95% CrI 18 fewer to 28 more, moderate certainty), probably increases adverse effects leading to drug discontinuation (RD 19 more per 1,000, 95% CrI 1 fewer to 70 more, moderate certainty) and may have no important effect on suspected, probable or laboratory-confirmed infection (RD 15 fewer per 1,000, 95% CrI 64 fewer to 41 more, low certainty). Due to serious risk of bias and very serious imprecision - and thus very low certainty evidence, the effects of ivermectin combined with iota-carrageenan on laboratory-confirmed infection (RD 52 fewer per 1,000, 95% CrI 58 fewer to 37 fewer), and ivermectin alone on laboratory-confirmed infection (RD 50 fewer per 1,000, 95% CrI 59 fewer to 16 fewer) and suspected, probable or laboratory-confirmed infection (RD 159 fewer per 1,000, 95% CrI 165 fewer to 144 fewer) remain uncertain.

ConclusionHydroxychloroquine prophylaxis does not have an important effect on hospital admission and mortality, probably increases adverse effects, and probably does not have an important effect on laboratory-confirmed SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, we are highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection.

Systematic review registrationThis review was not registered. The protocol established a priori is included as a supplement.

FundingThis study was supported by the Canadian Institutes of Health Research (grant

CIHR-IRSC:

0579001321).

Readers noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

BACKGROUND:

To date, there has been little agreement on what drug is the "best" drug for treating severe COVID-19 patients. This study aimed to assess the efficacy and safety of different medications available at present for severe COVID-19.

METHODS:

We searched databases for randomized controlled trials (RCTs) published up to February 28, 2022, with no language restrictions, of medications recommended for patients (aged 16 years or older) with severe COVID-19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all-cause mortality (ACM), and treatment-emergent adverse events (TEAEs).

RESULTS:

We identified 4021 abstracts and of these included 48 RCTs comprising 9147 participants through database searches and other sources. For decrease in ACM, we found that ivermectin/doxycycline, C-IVIG (i.e., a hyperimmune anti-COVID-19 intravenous immunoglobulin), methylprednisolone, interferon-beta/standard-of-care (SOC), interferon-beta-1b, convalescent plasma, remdesivir, lopinavir/ritonavir, immunoglobulin gamma, high dosage sarilumab (HS), auxora, and imatinib were effective when compared with placebo or SOC group. We found that colchicine and interferon-beta/SOC were only associated with the TEAEs of severe COVID-19 patients.

CONCLUSION:

This study suggested that ivermectin/doxycycline, C-IVIG, methylprednisolone, interferon-beta/SOC, interferon-beta-1b, convalescent plasma (CP), remdesivir, lopinavir/ritonavir, immunoglobulin gamma, HS, auxora, and imatinib were efficacious for treating severe COVID-19 patients. We found that most medications were safe in treating severe COVID-19. More large-scale RCTs are still needed to confirm the results of this study.

By 9 February 2021, the Coronavirus has killed 2,336,650 people worldwide and it has been predicted that this number continues to increase in year 2021. The study aimed to identify therapeutic approaches and drugs that can potentially be used as interventions in Coronavirus 2019 (COVID-19) management. A systematic scoping review was conducted. Articles reporting clinical evidence of therapeutic management of COVID-19 were selected from three different research databases (Google Scholar, PubMed, and Science Direct). From the database search, 31 articles were selected based on the study inclusion and exclusion criteria. This review paper showed that remdesivir and ivermectin significantly reduced viral ribonucleic acid (RNA) activity. On the other hand, convalescent plasma (CP) significantly improved COVID-19 clinical symptoms. Additionally, the use of corticosteroid increased survival rates in COVID-19 patients with acute respiratory distress syndrome (ARDS). Findings also indicated that both hydroxychloroquine and favipiravir were effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, lopinavir-ritonavir combination was not effective against COVID-19. Finally, ribavirin, galidesivir, and sofosbuvir showed potential therapeutic benefit in treating COVID-19, but there is a lack of clinical evidence on their effectiveness against SARS-CoV-2. Remdesivir, ivermectin, favipiravir, hydroxychloroquine, dexamethasone, methylprednisolone, and CP are the therapeutic agents that can potentially be used in COVID-19 management.

BACKGROUND:

Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations. Considering the particular impact of COVID-19 in the Americas, this document aims to present recommendations for the pharmacological treatment of COVID-19 specific to this population.

METHODS:

Fifteen experts, members of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) make up the panel responsible for developing this guideline. Questions were formulated regarding prophylaxis and treatment of COVID-19 in outpatient and inpatient settings. The outcomes considered in decision-making were mortality, hospitalisation, need for mechanical ventilation, symptomatic COVID-19 episodes, and adverse events. In addition, a systematic review of randomised controlled trials was conducted. The quality of evidence assessment and guideline development process followed the GRADE system.

RESULTS:

Nine technologies were evaluated, and ten recommendations were made, including the use of tixagevimab + cilgavimab in the prophylaxis of COVID-19, tixagevimab + cilgavimab, molnupiravir, nirmatrelvir + ritonavir, and remdesivir in the treatment of outpatients, and remdesivir, baricitinib, and tocilizumab in the treatment of hospitalised patients with severe COVID-19. The use of hydroxychloroquine or chloroquine and ivermectin was discouraged.

CONCLUSION:

This guideline provides recommendations for treating patients in the Americas following the principles of evidence-based medicine. The recommendations present a set of drugs that have proven effective in the prophylaxis and treatment of COVID-19, emphasising the strong recommendation for the use of nirmatrelvir/ritonavir in outpatients as the lack of benefit from the use of hydroxychloroquine and ivermectin.

Background Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations. Considering the particular impact of COVID-19 in the Americas, this document aims to present recommendations for the pharmacological treatment of COVID-19 specific to this population. Method Fifteen experts, members of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) make up the panel responsible for developing this guideline. Questions were formulated regarding prophylaxis and treatment of COVID-19 in outpatient and inpatient settings. The outcomes considered in decision-making were mortality, hospitalisation, need for mechanical ventilation, symptomatic COVID-19 episodes, and adverse events. In addition, a systematic review of randomised controlled trials was conducted. The quality of evidence assessment and guideline development process followed the GRADE system. Results Nine technologies were evaluated, and ten recommendations were made, including the use of tixagevimab + cilgavimab in the prophylaxis of COVID-19, tixagevimab + cilgavimab, molnupiravir, nirmatrelvir + ritonavir, and remdesivir in the treatment of outpatients, and remdesivir, baricitinib, and tocilizumab in the treatment of hospitalised patients with severe COVID-19. The use of hydroxychloroquine or chloroquine and ivermectin was discouraged. Conclusion This guideline provides recommendations for treating patients in the Americas following the principles of evidence-based medicine. The recommendations present a set of drugs that have proven effective in the prophylaxis and treatment of COVID-19, emphasising the strong recommendation for the use of nirmatrelvir/ritonavir in outpatients as the lack of benefit from the use of hydroxychloroquine and ivermectin.

Background: We provided a comprehensive evaluation of efficacy of available treatments for coronavirus disease 2019 (COVID-19). Methods: We searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database up to August 19, 2021. Randomized controlled trials for suspected or confirmed COVID-19 patients published on peer-reviewed journals were included, regardless of demographic characteristics. Outcome measures included mortality, mechanical ventilation, hospital discharge and viral clearance. Bayesian network meta-analysis with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs). Odds ratio (OR) was used as the summary measure for treatment effect. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by the treatment classifications. Results: We identified 222 eligible studies with a total of 102,950 patients. Compared with the standard of care, imatinib, intravenous immunoglobulin and tocilizumab led to lower risk of death; baricitinib plus remdesivir, colchicine, dexamethasone, recombinant human granulocyte colony stimulating factor and tocilizumab indicated lower occurrence of mechanical ventilation; tofacitinib, sarilumab, remdesivir, tocilizumab and baricitinib plus remdesivir increased the hospital discharge rate; convalescent plasma, ivermectin, ivermectin plus doxycycline, hydroxychloroquine, nitazoxanide and proxalutamide resulted in better viral clearance. From the treatment class level, we found that the use of antineoplastic agents was associated with fewer mortality cases, immunostimulants could reduce the risk of mechanical ventilation and immunosuppressants led to higher discharge rates. Conclusions: This network meta-analysis identified superiority of several COVID-19 treatments over the standard of care in terms of mortality, mechanical ventilation, hospital discharge and viral clearance. Tocilizumab showed its superiority compared with SOC on preventing severe outcomes such as death and mechanical ventilation as well as increasing the discharge rate, which might be an appropriate treatment for patients with severe or mild/moderate illness. We also found the clinical efficacy of antineoplastic agents, immunostimulants and immunosuppressants with respect to the endpoints of mortality, mechanical ventilation and discharge, which provides valuable information for the discovery of potential COVID-19 treatments.

OBJECTIVE:

To conduct a systematic review on the effectiveness and safety of pharmacological and nonpharmacological interventions, in the ambulatory setting, aimed at preventing severe disease in patients with COVID-19.

DATA SOURCES:

Electronic databases (PubMed, EMBASE, and EuropePMC) were searched on January 6, 2021.

STUDY SELECTION AND DATA EXTRACTION:

A systematic review was conducted, adhering to PRISMA guidelines. The quality of individual trials was assessed using the Cochrane Risk-of-Bias Tool 2, and the certainty of evidence was assessed using GRADE.

DATA SYNTHESIS:

The collective search retrieved 3818 citations. Eight trials relating to 9 pharmacological interventions were identified. No evidence for nonpharmacological interventions was identified. Low certainty evidence of effectiveness in preventing severe disease was found for fluvoxamine (absolute difference: -8.7%; 95% CI.: -1.8% to -16.4%) and bamlanivimab plus etesevimab (absolute difference: -4.9%; 95% CI.: -0.8% to -8.9%). Both trials were limited by small sample sizes and short durations of follow-up. In addition, very low certainty evidence of effect was found for ivermectin plus doxycycline and sulodexide. Based on published data, insufficient evidence of effect was found for bamlanivimab (monotherapy), casirivimab plus imdevimab, ivermectin (monotherapy), nitazoxanide, and peginterferon lambda.

RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE:

This review assessed all ambulatory treatments for COVID-19 that may improve patient outcomes and reduce hospitalizations.

CONCLUSION:

Recent trials have shown promising results for a number of pharmacological agents to treat COVID-19 in the ambulatory setting. However, larger, more robust trials are needed to support the routine use of these agents outside of monitored clinical trials.

OBJECTIVE:

To analyze the use of antimicrobial drugs in patients during the COVID-19 pandemic.

METHODS:

We searched for literature about antimicrobial treatment in COVID-19 patients through the Cochrane Library, Embase, PubMed, the Chinese biomedical literature database, CNKI, the Chinese journal full-text database, Wanfang, and Vipu. The quality evaluation of the literature was performed by Jadad's quality score.

RESULTS:

A total of three articles reported on ivermectin treatment in patients with COVID-19, and the Meta-analysis showed no clinical and statistical heterogeneity among the studies (I2 = 15%, P = .31), a fixed effect model was used to incorporate effect sizes. The clinical effect of the observed group was not different from the control group (P = .16). None of the three ivermectin articles with clinical effect as the effect indicator showed a significant difference (P > .05), suggesting no publication bias. A total of four publications reported the treatment with azithromycin in patients with COVID-19, and the Meta-analysis showed no clinical and statistical heterogeneity between the studies (I2 = 0%, P = .88), using a fixed-effect model to incorporate the effect sizes. The clinical effect of the observed group was not different from the control group (P = .57). None of the four azithromycin articles with a clinical effect as the effect index was statistically significant (P > .05), suggesting no publication bias.

CONCLUSION:

During the COVID-19 pandemic, the patient's use of antibiotics does not significantly improve clinical efficacy, so antibiotic use is recommended only for patients with complicated bacterial infections.