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Background Insight into COVID-19 intensive care unit (ICU) patient characteristics, rates and risks of invasive mechanical ventilation (IMV) and associated outcomes as well as any regional discrepancies is critical in this pandemic for individual case management and overall resource planning. Methods and findings Electronic searches were performed for reports through May 1 2020 and reports on COVID-19 ICU admissions and outcomes were included using predefined search terms. Relevant data was subsequently extracted and pooled using fixed or random effects meta-analysis depending on heterogeneity. Study quality was assessed by the NIH tool and heterogeneity was assessed by I2 and Q tests. Baseline patient characteristics, ICU and IMV outcomes were pooled and meta-analyzed. Pooled odds ratios (pOR) were calculated for clinical features against ICU, IMV mortality. Subgroup analysis was carried out based on patient regions. A total of twenty-eight studies comprising 12,437 COVID-19 ICU admissions from seven countries were meta-analyzed. Pooled ICU admission rate was 21% [95% CI 0.12–0.34] and 69% of cases needed IMV [95% CI 0.61–0.75]. ICU and IMV mortality were 28.3% [95% CI 0.25–0.32], 43% [95% CI 0.29–0.58] and ICU, IMV duration was 7.78 [95% CI 6.99–8.63] and 10.12 [95% CI 7.08–13.16] days respectively. Besides confirming the significance of comorbidities and clinical findings of COVID-19 previously reported, we found the major correlates with ICU mortality were IMV [pOR 16.46, 95% CI 4.37–61.96], acute kidney injury (AKI) [pOR 12.47, 95% CI 1.52–102.7], and acute respiratory distress syndrome (ARDS) [pOR 6.52, 95% CI 2.66–16.01]. Subgroup analyses confirm significant regional discrepancies in outcomes. Conclusions This is a comprehensive systematic review and meta-analysis of COVID-19 ICU and IMV cases and associated outcomes. The significant association of AKI, ARDS and IMV with mortality has implications for ICU resource planning for AKI and ARDS as well as suggesting the need for further research into optimal ventilation strategies for COVID-19 patients in the ICU setting. Regional differences in outcome implies a need to develop region specific protocols for ventilatory support as well as overall treatment.

Highlights Lactoferrin (Lf) is a naturally occurring, pleiotropic, non-toxic glycoprotein. Lf has broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. Lf shows in vitro antiviral activity against SARS-CoV, which is likely similar against SARS-CoV-2 via the same mechanism. Lf's immunomodulatory and anti-inflammatory effects may be especially relevant as a potential adjunct for severe COVID-19.

Bioactive polysaccharides occur extensively in TCM herbs and are the basis of potentially useful application of TCM as an adjuvant in cancer therapies.

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Background To characterize COVID-19 ICU admissions, their outcome and associated features, as well as identify their regional discrepancies. Methods Scopus, Embase, preprint servers bioRvix and medRvix and the Intensive Care National Audit and Research Center (ICNARC) website was searched for reports through May 1st 2020 on COVID-19 ICU admissions and outcomes using pre-defined search terms and eligibility criteria.Relevant data was extracted and pooled using fixed or random effects meta-analysis depending on heterogeneity. Study quality was assessed by the NIH tool and heterogeneity was assessed by I2 and Q tests. Baseline patient characteristics, ICU and IMV outcomes were pooled and meta-analyzed. Pooled odds ratios (pOR) were calculated for clinical features against ICU, MV mortality. Subgroup analysis was carried out based on patient regions.Results Twenty-eight studies comprising 12,437 COVID-19 ICU admissions from seven countries were meta-analyzed. Pooled ICU admission rate was 21%[95% CI 0.12 to 0.34] and 69% of cases needed IMV[95% CI 0.61-0.75]. ICU and IMV mortality were 28.3%[95% CI 0.25 to 0.32], 43%[95% CI 0.29 to 0.58] and ICU, IMV duration was 7.78[95% CI 6.99 to 8.63] and 10.12[95% CI 7.08 to 13.16] days respectively. Besides confirming the significance of comorbidities and clinical findings of COVID-19, major correlates with ICU mortality were found to be IMV [pOR 16.46, 95% CI 4.37 to 61.96], acute kidney injury (AKI) [pOR 12.47, 95% CI 1.52 to 102.7], and acute respiratory distress syndrome (ARDS) [pOR 6.52, 95% CI 2.66 to 16.01]. Subgroup analyses confirm significant regional discrepancies in outcomes.Conclusions This is the most comprehensive systematic review and meta-analysis of COVID-19 ICU and IMV cases and associated outcomes to date and the only analysis to analyze and associate IMV with COVID-19 ICU mortality. The significant association of AKI, ARDS and IMV with mortality has implications for ICU resource planning for AKI and ARDS as well as research into optimal ventilation strategies for patients. Regional differences in outcome implies a need to develop region specific protocols for ventilatory support as well as overall treatment.Study Registration PROSPERO registration number CRD42020182482.

The novel coronavirus 2019 pandemic is rapidly advancing despite public health measures. Pharmaceutical prophylaxis is an established approach to potentially control infectious diseases and is one solution to the urgent public health challenge posed by COVID-19. Screening and development of new vaccines and antivirals is expensive and time consuming while the repositioning of available drugs should receive priority attention as well as international government and agency support. Here we propose an old drug chloroquine (CQ) to be urgently repositioned as an ideal antiviral prophylactic against COVID-19. CQ has ability to block viral attachment and entry to host cells. Its proven clinical efficacy against a variety of viruses including COVID-19 and its current deployment in COVID-19 therapeutic trials strengthens its potential candidacy as a prophylactic. Furthermore, CQ has a long safety record, is inexpensive and widely vailable. Here we reviewed CQ's antiviral mechanisms, its laboratory efficacy activity against COVID-19, as well as CQ's pharmacokinetics in its established use against malaria and autoimmune diseases to recommend safe and potentially efficacious dose regimens for protection against COVID-19: a pre-exposure prophylaxis of 250-500mg daily and post-exposure prophylaxis at 8mg/kg/day for 3 days. We recommend further urgent research on CQ for COVID-19 prevention and urge that the above regimens be investigated in parallel with mass deployment by relevant agencies in attempts to contain the pandemic without unnecessary regulatory delays as benefits far outweigh risks or costs.

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