key: cord-355475-kdubhh73
authors: Patton, Lauren L.
title: Viral Pandemics and Oral Health: Lessons Learned From HIV to SARS-CoV-2
date: 2020-11-05
journal: Oral Surg Oral Med Oral Pathol Oral Radiol
DOI: 10.1016/j.oooo.2020.10.022
sha: 
doc_id: 355475
cord_uid: kdubhh73

nan

training was from James J. Crawford, PhD and I was memorably impacted by his "What if Saliva Were Red" video. Originally developed in the 1970s, this video graphically illustrated the widespread dissemination of the otherwise invisible saliva around the dental operatory during routine practice. From this dramatic demonstration, it became clear there was a need for improved cross-infection control practices to prevent infection with blood-borne pathogens. Until around the discovery of HIV in 1985, dentists typically wore gloves only for surgical and some endodontic procedures, long sleeve gowns were nonexistent in restorative dental practice, handpieces were not routinely autoclave sterilized, and masks and protective eyewear was rarely used in general dental settings. And yes, as we somewhat painfully adapt today to the extra gear, particularly the N95 respirator and full-face shields, in the 1980's we mourned the loss of fine tactile sensations with routine use of gloves. In the early AIDS pandemic, enhanced sterilization and engineering designs helped keep us safer from sharps injuries, dental unit waterline contamination and suction equipment backflow, and handpiece cross-contamination, as today enhanced air handling systems, face shields, and new office designs help to keep us safer in our aerosol generating environment. We have now added plexiglass barriers as social distancing/sneeze-guard shields to protect our main office staff, as lessons from our early use of disposable plastic cover barriers on operatory light handles, dental chairs and operatory trays/handpiece setups taught us how to simplify maintaining clean surfaces prone to contamination with potentially infectious agents. We now are challenged with quickly introducing more safety measures for our work in an environment of droplets and aerosols from the mouth in this age of a respiratory pandemic. An early survey in May and June 2020 of practicing dentists in private practice and public health settings in the United States (U.S.), a short 2 months after the first COVID-19 wave and national shortages of personal protective equipment caused offices to move to emergency only dental care, showed that 99.7% of offices had implemented enhanced infection control procedures. 1 These were most often more frequent disinfection, COVID-19 screening procedures including temperature checks, social distancing, and providing face masks to staff and patients. 1 Meeting the challenges of producing a safer office practice environment and educating the public and our dental team members on our risk mitigation strategies are helping overcome public fear of COVID-19 spread in the dental office. The early days of the AIDS pandemic were filled with fear of spread of AIDS in the dental office. A common practice in the early days of the AIDS pandemic among practices that would accept AIDS patients was providing care only at the end of the day so the invisible virus would dry and die on surfaces overnight. Uncertainty over many aspects of the new air-borne COVID-19 disease and the dramatically increased demand on a limited supply of personal protective equipment caused a shut-down of dental practices to only emergency dental services and limitations on use of aerosol-generating dental equipment. Today with practices reopened, a main concern is SARS-CoV-2 viral particles lingering in the air in the operatories, suggesting the need to allow time between patients for the room air to settle and/or implementation of high-efficiency particulate air filtration systems. Fortunately, with today's wide-spread influence of the internet, transition to electronic health records and patient engagement in health, many patients have the capacity for audio/video visits with their healthcare providers. These technological advances helped to transform the nascent telehealth system into one that is a robust alternative for triage and dental visits not requiring hands-on examination and procedural-based care, helping to solve healthcare access challenges.

As soon as vaccines became available against HBV, healthcare workers were immunized, and over a short time period vaccine technology moved from plasmaderived to recombinant DNA technology. 2 Despite globally wide-spread infant HBV vaccination programs implemented in the ensuing years, HBV has not been eradicated.

While HIV has eluded the efforts to develop a preventive vaccine largely due to its global genetic diversity, 3 SARS-CoV-2 has appeared to be relatively genetically stable, thus creating hope for success in efforts toward creation of a SARS-CoV-2 vaccine.

What would be most useful for prevention of future pandemics would be development of a vaccine that was widely effective against many alpha and beta human coronavirus strains. While hope for a COVID-19 vaccine to quell transmission is widespread, we must not lose sight of the fact that diverse vaccine development technologies and novel drug discovery efforts made today will benefit our response to the next pandemic. Given the length of time for drug and vaccine development and approval, we now need to commit to getting ahead of the curve with well-organized and funded collaborative efforts to add to the pipeline.

Molecular evidence of both viruses can be found in whole saliva fluids, although in lower concentration than in blood. Evidence supports SARS-CoV-2 to be community spread via saliva droplets and aerosols through coughing, sneezing, speaking, singing and breathing. 4 One of the key reasons for HIV testing advocacy was the observation that HIV-infected individuals unaware of their infection were the most likely to spread HIV; this is also true for SARS-CoV-2 where 80% of transmission may be due to undocumented asymptomatic infection. 5 Saliva based SARS-CoV-2 diagnosis of this enveloped, positive-sense, single-strand RNA virus by RT-PCR or immunoglobulin/antigen detection has emerged as a promising testing option to the traditional nasopharyngeal swab test. 4 It is likely that the work that went into developing the more recent generation antibody/antigen tests for HIV helped accelerate the pace of development of testing modes for SARS-CoV-2.

OraSure Technologies Inc. (Bethlehem, PA, USA) delved into saliva or oral-fluid based HIV antibody testing. Their efforts that moved from lab to rapid point-of-care to at-home testing over the course of several years have likely paved the way for more rapid progress and acceptance of saliva-based rapid SARS-CoV-2 testing. To date, one study analyzing multiple immunoglobulin response to SARS-CoV-2 in various biological fluids, including self-collected saliva for rapid SARS-CoV-2 diagnosis, has been published as a protocol without results, 6 so additional results of this study and others are needed to support antibody testing for SARS-CoV-2 in saliva. The real hope is for saliva-based point-of-care rapid tests, as was created in OraQuick Advance® HIV-1/2 (Orasure Technologies, Inc.) for diagnosis of HIV infection.

There has been limited progress in developing a specific treatment for COVID-19 at present despite advances in repurposing the nucleotide analog antiviral Remdesivir® and exploiting passive immunity approaches with production of convalescent plasma from recovered patient therapies or multiple neutralizing monoclonal antibody cocktails (Regeneron and Eli Lilly). It took considerable research investments and six years for approval of azidothymidine, the first antiretroviral drug in the fight against HIV, originally synthetized for use as a cancer treatment agent, and even longer until highly effective antiretroviral therapies were available. 7 We are just at the beginning of our human interaction with corona virus diseases and since cross-species transmission of viral pathogens has emerged as a threat to humans, 8 a sustained investment in antiviral research can better prepare us for the future. Our repurposing of today's antiviral drug discoveries fuels hope of more rapid solutions to future viral pandemics that are inevitable. 10 Of the different taste disorders, the most common was dysgeusia (38%), followed by 35% hypogeusia and 24% ageusia. 10 Authors of this review report that the diversity of oral mucosal lesion presentations including irregular and aphthous-like ulcers, white and erythematous plaques, blisters, petechiae, and desquamative gingivitis, found on the lips, tongue, palate, buccal mucosa and gingiva, suggest coinfections and secondary manifestations of COVID-19. patients. Interestingly, the dermatology literature is also demonstrating that vesicular rashes appear early and may help diagnosis, while vascular rashes may be useful in predicting severe disease. 13 To determine co-occurrence of skin lesions (exanthems) and oral cavity lesions (enanthem) in patients with COVID-19, oral cavities were examined in 21 patients with skin rashes and 6 (29%) had oral lesions, all on the palate, and described as macular and/or petechial, with no association with drug intake and laboratory studies suggested they were a stronger indicator of viral etiology than a drug reaction. 14 When the diversity of oral mucosal and salivary gland disorders were observed in HIV/AIDS patients, international collaborative groups such as the European Community We learned from HIV disease management that the antiretroviral drugs can have acute and long-term toxicities including ulcers, xerostomia/parotid lipomatosis, taste disturbances, perioral paresthesia, erythema multiforme and facial fat wasting. 16 Will there be oral toxicities or benefits of COVID-19 treatments particularly as treatments target the cytokine storm, a procoagulant state, and local and systemic activation of inflammation?

In this new global pandemic, we need to learn from early disease hotspots, and We have witnessed great strides in the early months of this pandemic when our U.S. National Institutes of Health created supplemental funding for existing extramural grants to add components related to the clinical impact of SARS-CoV-2 on patients' health outcomes. Internationally, as was the case at my home academic institution, many researchers engaged in and supported for their HIV/AIDS work pivoted to work on COVID-19. While many COVID-19 studies could be conducted in laboratory biosafety level 2 (BSL-2) laboratories using standard precautions, those studies involving virus isolation needed BSL-3 laboratories and procedures. 19 As this is similar to the biosafety categorization for work with HIV, 20 many already established BSL-3 laboratories engaged in HIV research became rapidly repurposed as COVID-19 research facilities.

Almost overnight, our HIV clinical researchers became COVID-19 researchers, as critical new studies were designed. Without HIV/AIDS, this research infrastructure needed for COVID-19 work would likely not have existed. We now need better mobilization of scientific collaboration globally and continued support of federal and international agencies to sustain our work in prevention and treatment for COVID-19 to prepare us for future outbreaks and sustain our global population. This is a global health crisis, needing a global response.

The COVID-19 pandemic has further revealed the fundamental place of dentistry in the health system as an essential health care service whose role is to assure eradication of disease and management of pain in the maxillofacial structures to preserve quantity and quality of life and to prevent decline in a person's systemic health. We have been effective at keeping patients with dental complaints out of our nation's hospital emergency departments during the early COVID-19 shut-downs. We have adapted and will continue to adapt to the challenges ahead. The question arises as to whether we can now mobilize our oral health team to participate in viral disease testing and vaccination efforts in the days ahead.

Here's hoping we have many "wins" in 2021 for our further integration into the health system.

Estimating COVID-19 prevalence and infection control practices among US dentists. JADA. Online ahead of print 15

Hepatitis B: 50 years after the discovery of Australia antigen

Global and regional molecular epidemiology of HIV-1, 1990-2015: a systematic review, global survey, and trend analysis

COVID-19 salivary signature: diagnostic and research opportunities

Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2)

Detection of SARS-CoV-2 RNA and antibodies in diverse samples: protocol to validate the sufficiency of Provider-Observed, Home-Collected blood, saliva, and oropharyngeal samples

Learning from history: do not flatten the curve of antiviral research! Drug Discov Today

Viruses in bats and potential spillover to animals and humans

ACE2 & TMPRSS2 Expressions in Head & Neck Tissues: A Systematic Review

Oral Manifestations in Patients with COVID-19: A Living Systematic Review

Oral lesions in patients with SARS-CoV-2 infection: could the oral cavity be a target organ? Oral Surg Oral Med Oral Pathol Oral Radiol

Report of four cases. Are they a true sign of COVID-19 disease? Spec Care Dentist

Cutaneous Manifestations of COVID-19: An Evidence-Based Review

Classification and diagnostic criteria for oral lesions in HIV infection. EC-Clearinghouse on Oral Problems Related to HIV Infection and WHO Collaborating Centre on Oral Manifestations of the Immunodeficiency Virus

Adverse effects of antiretroviral therapy: focus on orofacial effects

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Centers for Disease Control and Prevention. Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID-19). Available at

Agent Summary Statement for Human Immunodeficiency Viruses (HIVs) Including HTLV-III, LAV, HIV-1, and HIV-2