Guidelines

Opinion: Dentistry, Diagnostic Test Accuracy (DTA) and the Covid-19 Antibody Test

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Link to the Dental Elf

Virus Outbreak Germany

As we are acutely aware the whole country has been locked down in an attemp to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 (Covid-19)), while we restructure the healthcare systems and direct research funding into either a treatment and/or a vaccine. The next stage is to rapidly scale up diagnostic testing to collect robust base-rate data at both an individual, and population level for future high quality decision-making (Ioannidis, 2020). The need to know who has been infected will be particularily important for dental care professionals due to the potential risk of Covid-19 spread via aerosol generating procedures (Coulthard, 2020). So what is the current state of affairs regarding quick point-of-care antibody testing? How good is it, how good should it be, and why is this important?

Firstly I am going to use a recently published paper that evaluated 10 antibody tests for SARS-CoV-2 using Enzyme-Linked Immunosorbent Assay (ELISA) and Lateral Flow Immune Assay (LFIA), lateral flow assay utilise the same technology commonly used for pregnancy tests (Crook, 2020). This particular paper has sparked considerable controversy which I will go into later. If you need more detail on how these tests work and their advantages/disadvantages then please take a look at the Oxford COVID-19 Evidence Service (Green et al., 2020). When looking at diagnostic accuracy testing the two main concepts to understand are:

Sensitivity – The ability of a diagnostic test to give a positive result when it is supposed to be positive.

Specificity – The ability of a diagnostic test to indicate a negative result when it is supposed to be negative.

 Results

After extracting the primary data from the individual tests, meta-analysis was carried out using the ‘mada’ package in R. The summary estimate for sensitivity was 62.7% (95%CI: 57.5 to 67.7) and specificity 96.9% (95%CI: 95.2 to 98.0) The results for the ELISA test and the 9 LFIA tests were plotted below on to a Summary Receiver Operating Characteristic (sROC) curve ( See Figure 1). The y-axis represents the sensitivity (1.0 =100%), and the x-axis represents 1- specificity (0.10 = 10%). For a test to be perfect the summary estimate point should be in the top left corner representing 100% true-positives and 0% false-positives. The blue dot represents the summary estimate for the tests surrounded by a 95% confidence area, the red dot represents the specification target of >98% (95%CI: 96 to 100%)  for sensitivity, and >98% (95%CI: 96 to 100%) for specificity, set by the Medicines & Healthcare Products Regulatory Agency (MHRA., 2020).

Figure 1. sROC curve – Antibody tests

sROC_DT_1_LI (2)

Discussion

So why is so important to set the levels of sensitivity and specificity so high? Imagine we have a small city with a population of 100,000. The prevalence of people who have had the virus and recovered is 6%  and you are using an LFIA test with a sensitivity of 63% and specificity of 97%. Out of 6600 people who test positive for virus antibody only 3780 are true positives which corresponds to 57% having a correct positive diagnosis (See Figure 2.). Another important consideration is that 3% of the population who do not have antibodies test positive (n= 2820) and could lead them to believe they are immune.

Figure 2.Frequency tree of Covid-19 antibody screening

Annotation 2020-05-09 193854

The second point about this paper is that in its present format it cannot be used in any future analysis since the companies that supplied the tests required a commercial confidentiality agreement to be signed with the UK Department of Health making it impossible to discriminate between tests. The current set of results show poor performance, and that is why the MHRA has specifically set its targets high because of the risks that  results could pose if they were used to ease a lockdown, or they become part of an immunity passport system (Mahase., 2020; WHO, 2020). The final point is that whenever we have to deal with diagnostic tests or screening devices in either our professional or private lives we need to be able to identify the products, their comparators, and how accurate they are before making a significant decision to use or purchase the product. False-positive and false-negative results can pose significant harms to both ourselves and the population in general.

Disclaimer:  The article has not been peer-reviewed; it should not replace individual clinical judgement, and the sources cited should be checked. The views expressed in this commentary represent the views of the author and not necessarily those of the host institution. The views are not a substitute for professional advice.

References

COULTHARD, P. 2020. Dentistry and coronavirus (COVID-19) – moral decision-making. Br Dent J, 228, 503-505.

CROOK, D. W. 2020. Evaluation of antibody testing for SARS-CoV-2 using ELISA and lateral flow immunoassays [Online]. Department of Microbiology, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom.  [Accessed].

GREEN, K., , A. W., DICKINSON, R., GRAZIADIO, S., ROBERT WOLFF, MALLETT, S. & ALLEN, A. J. 2020. What tests could potentially be used for the screening, diagnosis and monitoring of COVID-19 and what are their advantages and disadvantages? [Online]. Available: https://www.cebm.net/covid-19/what-tests-could-potentially-be-used-for-the-screening-diagnosis-and-monitoring-of-covid-19-and-what-are-their-advantages-and-disadvantages/ [Accessed].

IOANNIDIS, J. P. 2020. A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data [Online]. STAT. Available: https://www.statnews.com/2020/03/17/a-fiasco-in-the-making-as-the-coronavirus-pandemic-takes-hold-we-are-making-decisions-without-reliable-data/ [Accessed].

MAHASE., E. 2020. Covid-19: Confidentiality agreements allow antibody test manufacturers to withhold evaluation results.

MHRA.2020.Target_Product_Profile_antibody_tests_to_help_determine_if_people_have_immunity_to_SARS-CoV-2_ [Online]. Available: https://www.gov.uk/guidance/guidance-on-coronavirus-covid-19-tests-and-testing-kits [Accessed].

WHO.2020. “Immunity passports” in the context of COVID-19 [Online]. Available: https://www.who.int/news-room/commentaries/detail/immunity-passports-in-the-context-of-covid-19 [Accessed].

Disclaimer: the article has not been peer-reviewed; it should not replace individual clinical judgement, and the sources cited should be checked. The views expressed in this commentary represent the views of the author. The views are not a substitute for professional medical advice.

 

What is the most appropriate gown/apron for preventing Covid-19 contaminated fluids transfer in dental practice?

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Originally posted on the Dental Elf

L0028811 A nurse and a surgeon, both wearing gown and mask. Etching b

Question:

Which gown/apron combination provides the best protection in the dental practice?

Bottom-line answer:

From this reanalysis of the primary data the reusable cotton surgical gown may be more practical in the dental environment in the long-term than the disposable fluid resistant gown due to its reduce potential for cross contamination during use. The plastic apron creates the most cross contamination and should only be used if there is significant risk of fluid contamination.

Background

This paper is a reanalysis of a recent systematic review (Verbeek et al., 2020) on personal protective equipment (PPE), reframing the question to fit into the new clinical workflow created by Covid-19, and dental aerosol generating procedures (AGPs). I have covered face masks in a previous post.

Much has been written on the epidemiology of Covid-19 and its transmissibility via contact, droplets, aerosols, or faeco-oral route. The main concern within dentistry being the aerosol generated during many routine dental procedures (Coulthard, 2020). To reduce this contamination risk Public Health England’s guidance document for personal protective equipment updated 3 May 2020 Section 10.4 (GOV.UK, 2020) states that:-

‘Disposable fluid repellent coveralls or long-sleeved gowns must be worn when a disposable plastic apron provides inadequate cover of staff uniform or clothes for the procedure or task being performed, and when there is a risk of splashing of body fluids such as during AGPs in higher risk areas or in operative procedures. If non-fluid-resistant gowns are used, a disposable plastic apron should be worn’.

As this advice is generic and the workflow within a critical care unit differs from a dental practice it is important to evaluate the best available evidence from a primary care rather than secondary care perspective.

Method

To save unnecessary duplication of search strategies and risk of bias/quality assessments I utilised the most up to date Cochrane Review of PPE for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff (Verbeek et al., 2020). This systematic review included 17 studies with 1950 participants evaluating 21 interventions. The authors concluded:

‘We found low- to very low-certainty evidence that covering more parts of the body leads to better protection but usually comes at the cost of more difficult donning or doffing and less user comfort, and may therefore even lead to more contamination. More breathable types of PPE may lead to similar contamination but may have greater user satisfaction.’

The authors conclusion helped to focus the next stage of analysis which was based around the levels of contamination and wearability. From the included studies two randomised simulation trials, one of a parallel design (Wong et al., 2004) and a second of a cross-over design (Guo et al., 2014) were selected as they contained sufficient primary data to undertake a meta-analysis. A simulation trial utilises aerosolised fluorescent dye sprayed on the PPE instead of true viral contamination. It was possible to extract data on contamination of  fluid resistant disposable gowns, standard cotton surgical gowns, and plastic aprons. The data was placed in Excel and then transferred to R for meta-analysis using the ’meta’ package. A random effect model was used with a Hartung Knapp conversion due to variability within the studies. Prediction intervals were included to facilitate the estimation for future studies.

Findings

The first meta-analysis compared a fluid resistant disposable gown with a standard cotton gown for both Wong and Guo. In Guo’s study the group tried two methods of doffing PPE: their individual accustomed removal method (IARM), and gown removal methods recommended by the Centers for Disease Control and Prevention (CDC).

The overall result favoured the cotton gown, but the result was non-significant, the mean difference (MD) was 0.91 (95%CI: -0.34 to 2.66) (See Figure 1.). The second meta-analysis showed significantly less contamination of the cotton surgical gowns compared with the plastic apron, the  MD was 8.4 (95%CI: 0.59 to 16.2) (See Figure 2.). The final analysis looked at the  contamination of the clinician post PPE removal showing equal contamination between the different PPE types MD was -0.02 (95% CI: -1.43 to 1.40) (See Figure 3).

Figure 1.Forest plot of disposable fluid resistant gown vs cotton gown

FIGURE 1

Figure 2. Forest plot of plastic apron vs cotton gown

FIGURE 2.

Figure 3. Forest plot of body contamination

 FIGURE 3

Conclusion

From the results of the meta-analysis there is little difference between the disposable fluid resistant gown and the reusable cotton surgical gown in terms of contamination/protection of both the wearer, patient, and clinical environment. The results favour the cotton gown as cotton through its material and properties can absorb droplet contaminants and thereby reduce opportunities for such contaminants to spread to the environment. The plastic apron performed worst and may significantly increase the risk of cross contamination both to the clinician and patient and should only be necessary where there is a risk of serious fluid contamination.

There is an interesting paper recently published by Phan and co-workers (Phan et al., 2019) who observed that ‘90% of observed doffing was incorrect, with respect to the doffing sequence, doffing technique, or use of appropriate PPE. Common errors were doffing gown from the front, removing face shield of the mask, and touching potentially contaminated surfaces and PPE during doffing’.

These results presented are hypothetical and due to the lack of specific studies of virus penetration through gowns in dentistry and are based on surrogate, and composite outcomes. There is an urgent need for specific studies to address PPE performance in the dental surgery environment.

Disclaimer:  The article has not been peer-reviewed; it should not replace individual clinical judgement, and the sources cited should be checked. The views expressed in this commentary represent the views of the author and not necessarily those of the host institution. The views are not a substitute for professional advice.

References

COULTHARD, P. 2020. Dentistry and coronavirus (COVID-19) – moral decision-making. Br Dent J, 228, 503-505.

GOV.UK. 2020. COVID-19 ( personal protective equipment (PPE) [Online]. Available: https://www.gov.uk/government/publications/wuhan-novel-coronavirus-infection-prevention-and-control/covid-19-personal-protective-equipment-ppe [Accessed].

GUO, Y. P., LI, Y. & WONG, P. L. 2014. Environment and body contamination: a comparison of two different removal methods in three types of personal protective clothing. Am J Infect Control, 42, e39-45.

PHAN, L. T., MAITA, D., MORTIZ, D. C., WEBER, R., FRITZEN-PEDICINI, C., BLEASDALE, S. C., JONES, R. M. & PROGRAM, C. P. E. 2019. Personal protective equipment doffing practices of healthcare workers. Journal of occupational and environmental hygiene, 16, 575-581.

VERBEEK, J. H., RAJAMAKI, B., IJAZ, S., SAUNI, R., TOOMEY, E., BLACKWOOD, B., TIKKA, C., RUOTSALAINEN, J. H. & KILINC BALCI, F. S. 2020. Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff. Cochrane Database Syst Rev, 4, CD011621.

WONG, T. K., CHUNG, J. W., LI, Y., CHAN, W. F., CHING, P. T., LAM, C. H., CHOW, C. B. & SETO, W. H. 2004. Effective personal protective clothing for health care workers attending patients with severe acute respiratory syndrome. American journal of infection control, 32, 90-96.

Other  links

Personal protective equipment: a commentary for the dental and oral health care team on  Verbeek et al .

Mouthwash; can it reduce levels of Covid-19 in the mouth?

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mouthwaskhttps://www.nationalelfservice.net/dentistry/oral-medicine-and-pathology/mouthwash-reduce-levels-covid-19-mouth/

Question:

In dental practice what is the most effective mouthwash for a patient to use to reduce the potential concentration of Covid-19 in the oral cavity ?

 

Bottom line answer: 

From this review  four mouthwashes were identified: 0.2% chlorhexidine mouthwash (CHX), 1% povidone iodine (PI) , 1.5% hydrogen peroxide (H2O2), or 0.05% hypochlorous acid (HOCl). CHX had poor virucidal properties and the other three (PI, H2O2,HOCl) all have good virucidal properties but poor microbial substantivity, with the benefits being lost within a few minutes as saliva flow may potentially replace the virus.  Of the three the most clinically acceptable in terms of virucidal activity, commercial availability, and taste is the 1.5% hydrogen peroxide.

Background

Two recent papers from China mention the potential use of chlorhexidine in prevention and control of aerosol transmission risk (An et al., 2020; Su, 2020) based on CDC guidelines (Kohn et al., 2003). There are also a number of papers identifying the presence of viral particles in the saliva of patients diagnosed with Covid-19 (Khurshid et al., 2020; Sabino-Silva et al., 2020; Xu et al., 2020).  Even though there is good evidence that chlorhexidine is effective at reducing  the bacterial count in bioaerosols derived from dental treatment (Shetty et al., 2013; Gupta et al., 2014; Santos et al., 2014; Swaminathan et al., 2014; Saini, 2015; Mohan and Jagannathan, 2016; Retamal-Valdes et al., 2017) it has poor virucidal activity (Farzan and Firoozi, 2019; Kampf et al., 2020). Two common oral mouthwashes have been suggested for the reduction of Covid-19, these being providone-iodine, and hydrogen peroxide, one further mouthwash mentioned was hypochlorous acid.

Method

In this rapid review, the authors searched via the electronic database Medline (Ovid) and Google Scholar for studies comparing the pretreatment use PI, H2O2, HOCl mouthwashes in the reduction in viral microorganisms in the oral cavity. Reviews, and papers investigating non-respiratory viruses were excluded. There was no restriction by language or publication or year (see Appendix A).

Results

Only one paper could be found relating to the antiviral capacity of common oral mouthwashes and that was Eggers and co-workers (Eggers et al., 2018) regarding povidone-iodine. This pharmaceutical industry funded study was carried out in-vitro using a povidone-iodine solution diluted to 0.23% and after 15 seconds it had produced a Log10 reduction factor for SARS-CoV, and MERS-Cov of  (A reduction of 39,811 copies/ml).

Discussion

To date there are no high-quality studies that have been peer reviewed or otherwise relating to the virucidal efficacy of commonly used oral mouthwashes. Having said that it is possible to hypothesize that both povidone-iodine and hydrogen peroxide do exhibit substantially more virucidal activity than chlorhexidine ( Log10 reduction factor of 0.6)  against  respiratory viruses  by a factor of 8000 times (Kampf et al., 2020). It must also be borne in mind that apart from chlorhexidine the other mouthwashes have poor substantivity allowing the oral microflora to reestablish within several minutes (Addy and Wright, 1978; Lafaurie et al., 2018). If the patient were to have Covid-19 the virus could potentially be replaced quite rapidly via the saliva (Khurshid et al., 2020; Sabino-Silva et al., 2020; Xu et al., 2020).

Therefore, of the three mouthwashes the most clinically acceptable in terms of virucidal activity, commercial availability, and taste is hydrogen peroxide. As a clinical workflow regarding restorative aerosol generating procedures the patient could be asked to rinse with 10 ml of 1.5% hydrogen peroxide for 1 minute prior to placement of the rubber dam and then the exposed surface of the teeth, and rubber dam swabbed down with hydrogen peroxide prior to treatment. These results are hypothetical and due to the lack of specific studies of the virucidal activity of mouthwashes in dentistry are based on surrogate, and composite outcomes. There is an urgent need for specific studies to address mouthwash use in the dental surgery environment.

Disclaimer:  The article has not been peer-reviewed; it should not replace individual clinical judgement, and the sources cited should be checked. The views expressed in this commentary represent the views of the author and not necessarily those of the host institution. The views are not a substitute for professional advice.

References

ADDY, M. & WRIGHT, R. 1978. Comparison of the in vivo and in vitro antibacterial properties of povidone iodine and chlorhexidine gluconate mouthrinses. Journal of clinical periodontology, 5, 198-205.

AN, N., YUE, L. & ZHAO, B. 2020. [Droplets and aerosols in dental clinics and prevention and control measures of infection]. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology, 55, E004.

EGGERS, M., KOBURGER-JANSSEN, T., WARD, L. S., NEWBY, C. & MÜLLER, S. 2018. Bactericidal and virucidal activity of Povidone-Iodine and chlorhexidine gluconate cleansers in an in vivo hand hygiene clinical simulation study. Infectious diseases and therapy, 7, 235-247.

FARZAN, A. & FIROOZI, P. 2019. Which Mouthwash is Appropriate for Eliminating Coronaviruses? A. Regeneration, Reconstruction & Restoratiion, 5.

GUPTA, G., MITRA, D., ASHOK, K. P., GUPTA, A., SONI, S., AHMED, S. & ARYA, A. 2014. Efficacy of preprocedural mouth rinsing in reducing aerosol contamination produced by ultrasonic scaler: a pilot study. Journal of periodontology, 85, 562-8.

KAMPF, G., TODT, D., PFAENDER, S. & STEINMANN, E. 2020. Persistence of coronaviruses on inanimate surfaces and its inactivation with biocidal agents. Journal of Hospital Infection.

KHURSHID, Z., ASIRI, F. Y. I. & AL WADAANI, H. 2020. Human Saliva: Non-Invasive Fluid for Detecting Novel Coronavirus (2019-nCoV). International journal of environmental research and public health, 17.

KOHN, W. G., COLLINS, A. S., CLEVELAND, J. L., HARTE, J. A., EKLUND, K. J. & MALVITZ, D. M. 2003. Guidelines for infection control in dental health-care settings-2003.

LAFAURIE, G., ZAROR, C., DÍAZ‐BÁEZ, D., CASTILLO, D., DE ÁVILA, J., TRUJILLO, T. & CALDERÓN‐MENDOZA, J. 2018. Evaluation of substantivity of hypochlorous acid as an antiplaque agent: A randomized controlled trial. International journal of dental hygiene, 16, 527-534.

MOHAN, M. & JAGANNATHAN, N. 2016. The efficacy of pre-procedural mouth rinse on bacterial count in dental aerosol following oral prophylaxis. Dental and Medical Problems, 53, 78-82.

RETAMAL-VALDES, B., SOARES, G. M., STEWART, B., FIGUEIREDO, L. C., FAVERI, M., MILLER, S., ZHANG, Y. P. & FERES, M. 2017. Effectiveness of a pre-procedural mouthwash in reducing bacteria in dental aerosols: randomized clinical trial. Brazilian oral research, 31, e21.

SABINO-SILVA, R., JARDIM, A. C. G. & SIQUEIRA, W. L. 2020. Coronavirus COVID-19 impacts to dentistry and potential salivary diagnosis. Clinical oral investigations, 24, 1619-1621.

SAINI, R. 2015. Efficacy of preprocedural mouth rinse containing chlorine dioxide in reduction of viable bacterial count in dental aerosols during ultrasonic scaling: A double-blind, placebo-controlled clinical trial. Dental Hypotheses, 6, 65-71.

SANTOS, I. R. M. D., MOREIRA, A. C. A., COSTA, M. G. C. & CASTELLUCCI E BARBOSA, M. D. 2014. Effect of 0.12% chlorhexidine in reducing microorganisms found in aerosol used for dental prophylaxis of patients submitted to fixed orthodontic treatment. Dental press journal of orthodontics, 19, 95-101.

SHETTY, S. K., SHARATH, K., SHENOY, S., SREEKUMAR, C., SHETTY, R. N. & BIJU, T. 2013. Compare the efficacy of two commercially available mouthrinses in reducing viable bacterial count in dental aerosol produced during ultrasonic scaling when used as a preprocedural rinse. Journal of Contemporary Dental Practice, 14, 848-851.

SU, J. 2020. [Aerosol transmission risk and comprehensive prevention and control strategy in dental treatment]. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology, 55, E006.

SWAMINATHAN, Y., THOMAS, J. T. & MURALIDHARAN, N. P. 2014. The efficacy of preprocedural mouth rinse of 0.2% chlorhexidine and commercially available herbal mouth containing salvadora persica in reducing the bacterial load in saliva and aerosol produced during scaling. Asian Journal of Pharmaceutical and Clinical Research, 7, 71-74.

XU, R., CUI, B., DUAN, X., ZHANG, P., ZHOU, X. & YUAN, Q. 2020. Saliva: potential diagnostic value and transmission of 2019-nCoV. International journal of oral science, 12, 11.

 

Appendix A. Medline (Ovid) Search strategy

Keyword Search result
1 exp *dentistry/ or exp *dental care/ 291185
2 (dental or oral or tooth or teeth).mp. 1138218
3 1 or 2 1179282
4 exp Mouthwashes/ 14314
5 ((oral or dental or mouth) adj3 (wash$ or rins$)).mp. 2899
6 (mouthrins$ or “mouth rins$”).mp. 2821
7 (rinse$ or rinsing$).mp. 14275
8 (mouthwash$ or “mouth wash$”).mp. 6676
9 5 or 6 or 7 or 8 19294
10 chlorhexidine/ 8265
11 chlorhexidine.mp. 12146
12 chx.mp. 3444
13 10 or 11 or 12 13721
14 Antiviral Agents/ 77993
15 exp Coronavirus Infections/ or exp Coronavirus/ 16185
16 3 and 9 10412
17 15 and 16 3
18 3 and 15 294
19 3 and 9 and 15 3
20 Saliva/ 41183
21 15 and 20 14
22 from 21 keep 1-3, 10-12 6
23 Hypochlorous Acid/ 2330
24 Povidone-Iodine/ 2817
25 Hydrogen Peroxide/ 57630
26 from 17 keep 1-3 3
27 virus.mp. or exp Viruses/ 1023534
28 16 and 23 and 27 1
29 16 and 24 and 27 0
30 16 and 25 and 27 0
31 chlorhexidine.mp. or exp Chlorhexidine/ 12146
32 16 and 27 and 31 11
33 from 32 keep 9, 11 2
34 16 and 23 9
35 from 34 keep 2, 4, 7 3

Editors Note:

A Cochrane rapid review related to this question is in development.

Antimicrobial mouthwashes (gargling) and nasal sprays to protect healthcare workers when undertaking aerosol generating procedures (AGPs) on patients without suspected or confirmed Covid-19 infection