COVID-19 Evidence Retrieval Service (CERS) is an initiative by the Faculty of Medicine University of Malaya. CERS is a platform that aims to assist clinicians by retrieving the best available evidence regarding COVID-19. This service is provided by a team of evidence-based medicine experts, librarians, doctors, and medical students.
If you have any clinical questions regarding COVID-19, please get in touch at https://bit.ly/askUMCERS and our expert team will answer your query with a WhatsApp message as soon as possible.
Disclaimer: The appraisals have not been peer-reviewed and represents the opinion of the individual appraiser and not of the University of Malaya. The appraisal summaries are not meant to provide real time answers to the clinical questions but serve as a platform to search for the best available evidence. They are not a substitute for sound clinical judgment or any institutional, national or international guidelines.
We try our best to answer all questions. However due to the large volume of questions coming in, we may not be able to answer every question.
If you have any questions about the appraisal(s) please email coviders@gmail.com
Q1: What is the accuracy of the COVID-19 RT-PCR diagnostic test?
A: This systematic review is limited by the lack of published studies and methodological issues but it identified one diagnostic validation study and potential rapid diagnostic tests in the offing.
Link: shorturl.at/vyJMZ
Literature searched on: 22 March 2020
Q2: What is the standardised personal protective equipment (PPE) method to combat COVID-19?
A: This systematic review shows that PPE with respirator (PAPR) compared to one without and gown compared to apron have better protection against contamination. However the systematic review is limited by single small simulation studies with high risk of bias and is not COVID-specific.
Link: shorturl.at/zQ278
Literature searched on: 22 March 2020
Q3: Mesenchymal stem cell treatment for COVID-19
A: MSC treatment is potentially beneficial and safe in COVID-19 patients but the evidence level is low and should be verified by a trial.
Link: shorturl.at/kzEXY
Literature searched on: 25 March 2020
Updated answer:
Link: shorturl.at/nvF05
(CEBM updated on 21 April 2020)
Literature searched on: 22 May 2020
Q4: How accurate is IgG/IgM COVID-19 rapid in detecting new infection in the first week?
A: COVID-19 IgM test has moderately high sensitivity (>80%) but result is uncertain due to the inclusion of many serum samples of patients with illness duration more than one week.
Link: shorturl.at/jlDHJ
Literature searched on: 29 March 2020
Updated answer:
A: Some rapid antibody test kits show reasonably high sensitivity and specificity but they are less likely to be able to detect COVID-19 infection in the first week.
Q5: If we use 3 surgical masks, the protection is equivalent to using N95 mask?
A: This systematic review is limited by comprehensive literature search and the included study has moderate to high risk of bias and is not COVID-19 specific.
Link: shorturl.at/adjM8
Literature searched on: 24 March 2020
Q6: Does anosmia has diagnostic value for COVID 19?
A: This scoping review is mainly limited by the lack of published studies. Nasal congestion is a common symptom of any viral infections, which may affect the sense of smell. Therefore, future adequately powered observational studies are required to demonstrate the associations of anosmia and COVID-19 infections. At this outbreak of Coronavirus, experts 2-4 proposed the use of anosmia as part of the screening questions for COVID-19 infection and subsequently activation of isolation if suggestive of COVID-19 to prevent the spread of this virus.
Link: shorturl.at/juAF8
Literature searched on: 23 March 2020
Updated answer:
A: This question has been covered by CEBM.
Link: shorturl.at/EIJQU
Literature searched on: 21 May 2020
Q7: Do hypertensive adults on ACEI having COVID-19 have better prognosis?
A: This question has been covered by CEBM and MOH Singapore rapid review teams.
Link: shorturl.at/awxyD
Literature searched on: 29 March 2020
Updated answer:
Link: shorturl.at/am016
(CEBM updated 31 March 2020)
Literature searched on: 4 June 2020
Q8: What is the effectiveness of hydroxychloroquine in reducing mortality and complications in patients with COVID-19?
A: CEBM has answered this as such: Several in vitro studies report antiviral activity of chloroquine and hydroxychloroquine against SARS-CoV-2. At present, there is insufficient in vivo evidence to recommend their use for the current pandemic outside of clinical trials. Further, high-quality studies are urgently needed to provide guidance to clinicians and policy-makers.
Link: shorturl.at/sBTW1
Updated answer
A: CEBM has also stated that: Current data do not support the use of hydroxychloroquine for prophylaxis or treatment of COVID-19. There are no published trials of prophylaxis. Two trials of hydroxychloroquine treatment that are in the public domain, one non-peer reviewed, are premature analyses of trials whose conduct in both cases diverged from the published skeleton protocols registered on clinical trial sites. Neither they, nor three other negative trials that have since appeared, support the view that hydroxychloroquine is effective in the management of even mild COVID-19 disease.
Link: shorturl.at/gvBDY
Literature searched on: 23 April 2020
Q9: What is the treatment effect of Vitamin C for COVID-19?
A: There is no published evidence as yet on the preventive or therapeutic effect of vitamin C on COVID-19 infection.
Link: shorturl.at/coHUV
Literature searched on: 3 April 2020
Updated search: 24 May 2020
No new evidence.
Q10: What is the most effective way to triage patient with suspected COVID 19?
A: WHO guideline outlines a comprehensive pathway of screening and triage of suspected COVID-19. However, there is no systematic review or study that examine the most effective way of screening and triage on patients with suspected COVID-19 infection.
Link: shorturl.at/yAFHZ
Literature searched on: 22 March 2020
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Updated search: 22 May 2020
To date, there was no study assessing the effectiveness of different methods of triage process on patients with suspected COVID-19.
Q11: Should the public wear mask to protect others as some may be asymptomatic or mildly symptomatic?
A: Although the review methodology was robust, the review is non-COVID specific studies and was performed nine years ago. The majority of the studies included are at moderate and high risk of bias.
Link: shorturl.at/iAHQ9
Literature searched on: 2 April 2020
Q12: By transfusing severe COVID-19 patient with plasma of those recovered from COVID-19, what is the prognosis?
A: The Ministry of Health, Singapore has answered this as such: There is currently limited published evidence on the use of CP for treating COVID-19 infection. Studies are underway with results expected later this year. Evidence to date for convalescent plasma (including H-IVIG) is for the treatment of other viral infections with mixed results. Positive survival benefit is based on small, low-quality studies and case reports, while two RCTs in severe influenza do not show any significant benefit.
Link: shorturl.at/hklq2
Literature searched on: 17 April 2020
Updated answer:
Link: shorturl.at/fpI57
(MoH Singapore updated 18 May 2020)
Literature searched on: 4 June 2020
Q13: Is Kaletra-Lopinavir/Ritonavir an effective treatment option for COVID-19?
A: Addition of lopinavir-ritonavir to standard care does not produce clinical improvement and does not reduce mortality in patients with severe COVID-19 patients.
Link: shorturl.at/vLT39
Literature searched on: 29 March 2020
Updated answer:
Link: shorturl.at/mvABR
(CEBM updated 14 April 2020)
Literature searched on: 4 June 2020
Q14: In view of the limitation in performing RT-PCR tests, is there any role of Rapid test under specific criteria? What should be the criteria?
A: There are rapid point of care tests being developed for the detection of COVID 19. However, evidence of their performance in clinical settings is lacking.
Link: shorturl.at/vMOX7
Literature searched on: 8 April 2020
Updated answer:
A: This systematic review found that current commercially available point-of-care diagnostic tests for SARS-CoV-2 antibodies (IgM/IgG) had low sensitivity and high specificity. The tests also correlated weakly with the gold standard RT PCR. This makes such tests unsuitable for clinical decision making.
Link: https://www.mdpi.com/2077-0383/9/5/1515
Literature searched on: 22 May 2020
Q15: What healthcare workers’ practices reduce transmission of respiratory infections to family members?
A: While results of the systematic reviews were related to respiratory infections, it seems reasonable to extrapolate these results to SARS-CoV-2. The benefits of healthcare workers practices such as social distancing, hand hygiene and wearing masks are self‐evident, however, they do require quantifying. There is a lack of evaluation on social distancing interventions. The current evidence suggests that surgical masks are adequate for the general public and non-high risk medical staff that do not have close contact with COVID-19 patients. Respiratory masks are recommended for high risk encounters especially with patients suspected of or confirmed cases. It should be noted that masks are only one aspect of personal protection equipment measures; where appropriate, it needs to be accompanied by other behavioural and infection control measures.
Link: shorturl.at/rtuOU
Literature searched on: 6 April 2020
Q16: What is the mental health risk among the public during a lockdown?
A: Although this review provides a comprehensive review of the psychological implications of quarantine, all the included studies were not assessed for risk of bias and there was a potential risk of publication bias.
Link: shorturl.at/ehkWY
Literature searched on: 23 March 2020
Updated search: 22 May 2020
No new evidence.
Q18: Can CPAP be used for patients who require oxygen support in COVID-19?
A: CPAP possibly has a role in the management of the hypoxaemic COVID-19 patient. The evidence is derived from experience with non-COVID-19 patients.
Link: shorturl.at/hjWZ8
Literature searched on 13 April 2020
Updated answer:
A; Indirect and low-certainty evidence suggests that the use of non-invasive ventilation (NIV) probably reduces mortality. Possible increased risk for transmission of COVID-19 to health care workers is noted.
Link: doi:10.7326/M20-2306
Literature searched on: 14 June 2020
Q19: Is early endotracheal intubation the choice for patients with developing respiratory failure?
A: At present, there is no recommendation on the early endotracheal intubation for patients with developing respiratory failure. The decision for early endotracheal intubation is at the discretion of treating clinicians, depending on the clinical response of treatment or severity of clinical presentation.
Link: shorturl.at/bBKV2
Literature searched on: 14 April 2020
Q20: Is there evidence for NIV in COVID-19 management?
A: NIV reduced endotracheal intubation rate and hospital mortality in patients with acute hypoxemic nonhypercapnic respiratory failure [mild category] but this is not COVID specific where there are concerns regarding infection control.
Link: shorturl.at/gCJP0
Literature searched on: 15 April 2020
Q17: What is the risk of vertical transmission to neonate for a COVID positive mother compare to PUI mother?
A: The methodology used to conduct the review was not robust and there is no primary study. Thus the quality of evidence for the above finding is low.
Link: shorturl.at/dptKZ
Literature searched on: 7 April 2020
Q21: Is there any guide available for triaging away patients in a primary care clinic?
A: There is inadequate data to recommend a triage strategy for in-person assessment of potential COVID-19 patients in primary care.
Link: shorturl.at/ckCVX
Literature searched on: 19 April 2020
Q22: How effective is ultraviolet (UV) light system for room sterilization or decontamination?
A: There is no firm conclusion that ultraviolet light system is effective for room sterilization and decontamination as the majority of data were synthesized from non-randomized studies or studies of before-and-after quasi experimental studies, which are subjected to multiple biases.
Link: shorturl.at/aeHW5
Literature searched on: 18 April 2020
Q23: What chemical(s) is suitable for use in Disinfection Chamber/ Booth/ Tunnel?
A: There are no relevant scientific studies to answer this clinical question.
Literature searched on: 18 April 2020
Updated answer:
Various disinfectants can kill coronavirus. However, it is unlikely that the disinfectants used in a disinfection box/chamber will be effective against coronavirus that has already entered the human body.
Link: shorturl.at/ahQRS
Literature searched on: 7 May 2020
Q24: What is the best method to sanitize N95 masks for reuse in the primary care setting?
A: Decontamination of N95 respirator can be achieved by various methods (Ultraviolet germicidal irradiation, microwave, and heat-based methods) with variation in the maintenance of function and mask fit. The Autoclaving of N95 respiratory is not appropriate. Do note that the papers used are pre-prints and have not yet been peer-reviewed.
Link: doi:10.31219/osf.io/4whsx
Literature searched in: 24 April 2020
Q25: What are the commonest clinical features of COVID-19?
A: CEBM has answered as such: Fever and cough are the two most common symptoms present in COVID-19. Other common symptoms are reported includes headache, rhinorrhea, gastrointestinal symptoms, sore throat, and fatigue.
Link: shorturl.at/cdsO6
Literature searched on: 24 April 2020
Q26: How frequent should we do surveillance sampling for our HCW (who are asymptomatic and managing PUI/COVID19)?
A: No relevant scientific studies have examined the frequency of surveillance sampling for our HCW (who are asymptomatic and managing PUI/COVID19)
Literature searched on: 24 April 2020
Q27: What will be the suitable disinfectant use on human in order to kill COVID present on clothing and external organ i.e. hair, parts of body etc?
A: No evidence to support the use of disinfectants on the clothing or body surfaces of human as a method to kill SARS-CoV-2.
Literature searched on: 26 April 2020
Q28: Is there any guide available for triaging away patients in a primary care clinic?
A: During a disaster such as a pandemic, resources are scarce and there is a need to allocate these scarce resources carefully. The main conclusion by the authors was that it is important to avoid making arbitrary decisions when considering the issue of triaging patients during a disaster. However, most of the included articles were of low quality. Also, this evidence is not COVID specific and addresses the ethical issues rather than the method to triage patients appropriately.
Link: shorturl.at/jpPTV
Literature searched on: 18 April 2020
Q29: What are the sensitivities and specificities of different gene focus (N gene, E gene, RdRp gene etc), for PCR in differentiating SARS-CoV-1 from other coronaviruses?
A: The existing practices in detecting genetic material of coronaviruses reported that E gene and RdRp gene assays to be highly sensitive and specific in differentiating SARS-CoV-1 from other coronaviruses in PCR.
Link: shorturl.at/mosx1
Literature searched on: 7 April 2020
Q30: How common is anosmia?
A: Loss of smell is highly prevalent in COVID-19 patients. The presence of anosmia can help to distinguish between COVID-19 and non-COVID patients.
Link: https://doi.org/10.1002/alr.22587
Literature searched on: 30 April 2020
Q31: After a positive COVID patient tested negative; a couple of times, are they really clear of COVID especially antibody, faeces, etc?
A: A small follow up study in China (n=20 patients) showed viral RNA was detected in 15% on Day 7 but all were cleared of the virus by Day 14.
Link: doi: 10.1007/s11606-020-05822-1
Literature searched on: 3 May 2020
Q32: What is the earliest time for PCR to be positive after a person is contracted with COVID-19 viruses?
A: No relevant evidence from the human COVID-19 study.
Link: shorturl.at/fkDR4
Literature searched on: 5 May 2020
Q33: Is there any level of viral load that we can safely say that the COVID-19 patient will not be able to transmit the disease even though their RT PCR is still positive?
A: No relevant scientific studies focus on the safe infective threshold of COVID-19 viral load despite their PT PCR remains positive.
Literature searched on: 7 May 2020
Q34: Is hand sanitization using disinfectant with little alcohol effective to kill virus i.e less 99%?
A: Studies show that hand rub products with an alcohol content of at least 70% reduced SARS virus load by 3 log units (99.9% of bacteria had been removed). This is not specific to COVID but can be extrapolated as SARS is a similar coronavirus.
Link: shorturl.at/fyHMO
Literature searched on: 7 May 2020
Q35: What is the association between smoking and COVID-19 to get a severe disease?
A: CEBM states that current evidence on smoking and severity of COVID-19 is inconclusive. Nevertheless, smoking is a risk factor for a range of comorbidities, many of which are associated with worse COVID-19 outcomes.
Link: shorturl.at/pqtVY
Literature searched on: 30 April 2020
Q36: The incubation period for covid-19 is 14 days. What is the recommendation for screening asymptomatic individuals who have been exposed beyond the incubation period?
A: No relevant studies or guidelines are found regarding laboratory testing after 14 days of home quarantine if the exposed person is asymptomatic.
Link: shorturl.at/xFN04
Literature searched on: 1 May 2020
Q37: Does the asymptomatic carrier have immunity if being exposed again in the future?
A: No relevant studies found.
Link: shorturl.at/gBJV8
Literature searched on: 3 May 2020
Q38: Does recovery confer lifelong immunity?
A: No evidence that recovery confers lifelong immunity from COVID.
Literature searched on: 3 May 2020
Q39: What is the reinfection rate of COVID-19?
A: A case series of 55 COVID-19 in China found a prevalence of 9% having reactivation. The incidence of reactivation cannot be determined.
Link: shorturl.at/hvyOS
Literature searched on: 13 May 2020
Q40: How does different type of rapid test kit affect the detection rate of COVID-19 cases?
A: This question has been covered by the CEBM (Molecular and antibody point-of-care tests to support the screening, diagnosis and monitoring of COVID-19).
Link: shorturl.at/hjyP6
Literature searched on: 15 May 2020
Q41: Which COVID-19 symptoms are associated with severe disease?
A: Dyspnoea is statistically significantly associated with severity of COVID-19.
Link: shorturl.at/jGPY8
Literature searched on: 12 May 2020
Q42: What is the minimal material requirement for PPE?
A: PPE material with good water repellency and water resistance, and poor air permeability is effective in providing a desirable protective function against droplet splash. However this type of material might be uncomfortable because of poor air permeability.
Link: shorturl.at/pBHKY
Literature searched on: 20 May 2020
Q43: Can diathermy convert bodily fluid into aerosol during surgery?
A: Electrocautery in tissue with potential high viral loads, i.e. aerodigestive tract, should be considered as a droplet forming procedure and as an AGMP.
Strength of evidence: moderate
Link: doi:10.1186/s40463-020-00425-6
Literature searched on: 20 May 2020
Q44: What level of antibody titre indicates immunity to COVID-19?
A: Review of coronavirus (non-COVID-19) studies revealed some protection from prior infection but a clear-cut protect neutralizing antibody level was not established.
Link: shorturl.at/ezSX2
Literature searched on: 21 May 2020
Q45: Can we wear 2 pieces of 3 ply surgical mask to replace N95??
A: There is no study available to determine if two surgical masks can replace N95 mask. However, there is a study comparing surgical masks and N95. This study shows there is a low level of evidence that medical masks and N95 respirators provided a similar level of protection against viral respiratory infections.
Link: shorturl.at/eglq7
Literature searched on: 12 May 2020
Q46: What is the evidence of extension of clinic practice hours in prevention of COVID-19 transmission?
A: At present, there was no evidence found on the extension of clinic practice hours in the prevention of COVID19 transmission.
Literature searched on: 5 June 2020
Q47: Who is more infectious? A symptomatic COVID19 patient or an asymptomatic COVID19 patient?
A: Epidemiologic, virologic and modelling evidence suggest that SARS-CoV-2 can be transmitted by persons with presymptomatic or asymptomatic infection, but as to who is more infectious, the evidence is still unclear.
Link: shorturl.at/dguxz
Literature searched on: 6 May 2020
Q48: How effective is school closure to reduce transmission COVID-19 among school-going children?
A: Existing studies cannot accurately determine the effectiveness of school closure to prevent COVID-19 transmission. There is a possibility of the small benefit of school closure based on modelling studies in UK.
Link: shorturl.at/sHJY7
Literature searched on: 11 June 2020
Q49: What is the long term effect to the lungs for a recovered mild COVID-19 infected patient (that did not require oxygen support)?
A: No studies reporting long term pulmonary effects in mild COVID infection. However, there was some indirect evidence that a majority showed improvement in lung imaging from a retrospective cohort study. Indirect evidence from a literature review on SARS and MERS reported that those with other coronaviruses did continue to have abnormalities of chest imaging but this was not with regards to mild disease.
Link: shorturl.at/fhvz7
Literature searched on: 19 June 2020
Q50: What are the outcomes/complications of non-COVID patients during a pandemic?
A: The current evidence points to potential mortality excess found among patients due to both COVID-19 or non-Covid 19. More reliable data is required to accurately determine and quantify them. To date, no data is reported on other morbidities or complications.
Link: https://www.bmj.com/content/369/bmj.m1809
Literature searched on: 27 May 2020