Background. Pooled testing has been implemented on a limited scale, mainly for screening and surveillance in populations with a low prevalence of COVID-19 to save on limited resources. Objective. To determine the diagnostic accuracy of pooled compared with individual RT-PCR testing for SARS-CoV-2 in individuals suspected of COVID-19. Methods. We searched websites of living CPGs on COVID-19 (Australian COVID-19, COVID NMA, CEBM Oxford), Philippine DOH HTA, databases (PubMed, CENTRAL, medRXIV/bioRXIV), and Clinicaltrials.gov for studies that used pooled testing on individuals suspected of COVID-19. When appropriate, we pooled data for sensitivity and specificity and obtained the range and median of other data, such as positive predictive value and resource savings. We did a priori subgroup analysis for pool size, presence or absence of symptoms and use case, type of specimen, cutoff for positivity, type of kit, and post hoc subgroup analysis for method of pooling and timing of processing. Results. We included 21 studies: 6 diagnostic accuracy studies, and 15 clinical validation studies. Studies had varying populations, index test kit and performance characteristics, positivity rate (0.02 to 15%), and pool size (5 to 16). There was moderate pooled sensitivity, 81% (95% CI 72, 88; I2=73.6%; 6 studies, 776 pools) and high pooled specificity, 99% (95% CI, 98 to 100; I2=1.84%; 5 studies, 666 pools). Positive predictive value based on 21 studies ranged from 67% to 100%. Resource savings in the number of test kits used ranged from 49 to 89%. Identified harms of pooled testing were delayed turnaround time for positive samples and laboratory errors. Conclusion. There is moderate sensitivity and high specificity with pooled testing for the screening of individuals with suspected COVID-19. We recommend further studies to validate the utility based on community prevalence and other test variables.
Background. Pooled data from observational studies suggest that patients with serum vitamin D levels below 30 ng/mL had an increased risk of infection and mortality from COVID-19. This rapid review aimed to determine the efficacy and safety of vitamin D as an adjunct treatment for COVID-19. Methods. We searched MEDLINE (PubMed) and CENTRAL up to July 18, 2021. We also searched trial registries, gray literature, and reference lists of included and excluded studies in the search as well as COVID-19 guidelines. Two reviewers independently screened titles and abstracts, collected data, and assessed for risk of bias. Meta-analysis was conducted, and an evidence profile table using GRADEpro was generated. Outcomes included were mortality, need for mechanical ventilator or progression of oxygen support, duration of mechanical ventilation, ICU admission, hospital length of stay, SARS-CoV-2 positivity at day 21, and adverse events. Results. We found four RCTs (3 low risk of bias and 1 high risk of bias). The sources of bias among the RCTs were unclear allocation, lack of blinding of patients, caregivers, and outcome assessors, and high drop-out rate. This rapid review found that the effects of vitamin D are inconclusive for the following outcomes: mortality (pooled RR 0.62, 95% CI [0.16 to 2.41], I2=49%; n=443, 3 RCTs, very low certainty of evidence), need for mechanical ventilator or progression of oxygen support (RR 0.52, 95% CI [0.24 to 1.13], n=237, 1 RCT, low certainty of evidence), and ICU admission (pooled RR 0.37, 95% CI [0.09 to 1.61], I2=78%; n=443, 3 RCTs, very low certainty of evidence. No significant reduction in hospital length of stay was found among those treated with vitamin D (MD 0 days, 95% CI [-1.19 to 1.09], low certainty of evidence). The duration of mechanical ventilation was also was also not significantly shortened in the treatment group (15 days) compared with placebo (12.8 days), MD 2.2 days, 95% CI [-8.4 to 12.8], low certainty of evidence. Interestingly, a higher proportion of those supplemented with vitamin D showed virologic clearance for COVID-19 on day 21 (RR 3.0, 95% CI [1.26 to 7.14], n=40, 1 RCT). At dosages between 60,000 to 200,000 IU of cholecalciferol, only one episode of vomiting (0.8%) was reported. Conclusion. Based on the evidence found, we are uncertain whether vitamin D is beneficial or harmful for patients with COVID-19. There is very low certainty of evidence to recommend the use of vitamin D supplements as an adjunct treatment for patients with COVID-19. Vitamin D supplementation for patients with COVID-19 should be limited to clinical trials or among those with proven vitamin D deficiency. More published studies are awaited to explore the benefit or harm of vitamin D for COVID-19.
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