Not since the human immunodeficiency virus (HIV) and the acquired immune deficiency
syndrome (AIDS) pandemic began, have we had a transformative experience in dentistry
that has made us deeply reexamine our practices and come to terms with a new reality
of how dentists care for their patient's health. What is different now than in 1985
is the more rapid pace of research and broad global public emphasis on conquering
the severe acute respiratory coronavirus 2 (SARS-CoV-2) that causes Corona Virus Disease
of 19 (COVID-19), and limiting its spread that results in damage to both our health
and finances. Both are pandemics to be reckoned with. HIV introduced the enduring
era of blood-borne pathogens and now SARS-CoV-2 has brought us into the era of respiratory
pathogens. While HIV targets lymphocytes and immune function and SARS-CoV-2 targets
the angiotensin-converting enzyme 2 (ACE-2) widely expressed receptor cells and the
renin-angiotensin system, lessons from our experience with HIV can inform aspects
of our response to the highly infectious SARS-CoV-2.
Enhanced infection control
Dentists, who at the start of the AIDS pandemic were described as working in a confined
dark contaminated space with sharp instruments, have of necessity established themselves
as experts in infection control practices, which have continued to evolve over time.
I began dental school training the University of North Carolina at Chapel Hill in
1982 at the nascence of the AIDS pandemic, when the hepatitis B virus (HBV) was the
main infectious disease of concern at the time. My infection control 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.
A race for vaccines for prevention
As soon as vaccines became available against HBV, healthcare workers were immunized,
and over a short time period vaccine technology moved from plasma-derived 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.
Salivary diagnostics
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.
Therapeutics
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.
Head and neck findings
Dysgeusia and anosmia have resulted from this new viral infection's destruction of
target nerves in the gustatory and olfactory sensory systems. Evidence now supports
glial and neuronal stem cell invasion of ACE2, which is the main host cell receptor
of the SARS-CoV-2 virus, and a secondary receptor, transmembrane protease serine-2
(TMPRSS2), explaining the development of dysgeusia and anosmia.
9
Head and neck involvement of COVID-19 extends beyond the changes in taste and smell.
ACE2 and TMPRSS2 receptor expression, enabling viral entry into the host and clinical
expression of disease, has been found in human major and minor salivary glands and
oral epithelium, including epithelial cells, fibroblasts, T cells and B cells.
9
A recent living systematic review of literature published through June 6, 2020 of
the prevalence of oral signs and symptoms in COVID-19 patients, involving 10,228 patients
in 19 countries, demonstrated the most common finding was gustatory impairments in
45%, suggesting this condition should be considered important in the clinical picture
of COVID-19’s initial presentation and disease progression.
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.
Nearly every month, new reports are revealing oral lesions possibly or probably associated
with COVID-19 infection, with a predominance of attention increasingly placed on hemorrhagic
and aphthous-like ulcerations with necrosis
11
and vesiculobullous and macular lesions.
12
Cruz Tapia and colleagues
11
suggest their four cases of angina bullosa hemorrhagica-like lesions, vascular disorder
and nonspecific stomatitis, support thrombi formation and vasculitis in the oral mucosa
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 (EC)-Clearinghouse
on Oral Problems Related to HIV Infection and World Health Organization (WHO) Collaborating
Centre on Oral Manifestations of the Immunodeficiency Virus gathered to reach consensus
on presumptive and definitive diagnostic criteria of multiple lesions and to classify
them according to levels of association with HIV from strongly associated, less commonly
associated, to those seen in HIV infection.
15
As more becomes known about oral manifestations of SARS-CoV-2, vaccination efforts
continue slowly, and future coronavirus infections/pandemics are likely, the need
may arise for an international collaborative consensus to be reached for defining
and classifying oral lesions and the dysgeusia/anosmia that is becoming more characteristic
of COVID-19. Will global teleconferencing be used to gather this expert data-driven
consensus? Similar to patients who have HIV infection, the host immune response to
SARS-CoV-2 likely impacts COVID-19 disease expression and clinical course of disease
in the oral cavity.
COVID-19 disease sequelae are not fully understood
SARS-CoV-2 is not known to result in chronic infection, yet many post-COVID-19 symptoms
including myocardial and neurological consequences are suggested. Medium and long-term
consequences of infection, particularly if severe disease manifestations, are yet
unexplored. Are there persistent autoimmune sequelae? What is the trajectory of recovery
of smell and taste? Are relapses or reinfections possible? Will there be other neurological
or neurovascular delayed diseases? Is there potential for SARS-CoV-2 virus to hone
to cranial nerves such as in the case of varicella-zoster virus contracted as varicella
(chicken pox) and lying dormant in the dorsal root ganglia of the trigeminal nerve
that reactivates a life-time later as shingles (herpes zoster)? Will there be common
or rare long-term sequelae? Can we determine who is at greatest risk? Are underlying
mechanisms of SARS-CoV-2 infection expressed as immunologic disease manifestations
that may become more apparent with aging of recovered patients? Are there preventive
approaches that can be developed to alleviate subsequent clinical disease expression?
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?
We are better together
In this new global pandemic, we need to learn from early disease hotspots, and continually
reassess successes and failures of varied prevention, diagnosis and treatment approaches.
In the U.S., both HIV and SARS-CoV-2 infection rates and deaths tend to be higher
among people of color, those living in poverty, and other vulnerable populations.
As with HIV, many more SARS-CoV-2 infected individuals are asymptomatic in disease
expression. Fortunately, we believe SARS-CoV-2 is cleared from the body with time
and an antibody response to the virus may provide protection in most people from further
infection and disease progression.
To give a global perspective of relative disease burden, the WHO reports an estimated
38 million (31.6-44.5) globally were living with HIV at the end of 2019; 1.7 million
(1.2-2.2) were newly infected with HIV in 2019 and there were 690,000 (500,000-970,000)
HIV-related deaths in 2019.
17
Although likely underestimates, the WHO similarly reports COVID-19 cases for the year
of 2020 to already exceed 2019 HIV cases at 42.5 million, as we enter the second Fall
2020 wave, with confirmed COVID-19 deaths at 1,147,301 (for 2020 with the first case
reported on January 4, 2020 through October 25, 2020).
18
This means deaths from COVID-19 this year are approaching double the number of annual
deaths last year from HIV.
This will happen again. Who will take the lead?
With viruses constantly mutating and evolving and people living in closer proximity
to animals, our future likely holds the possibility of new strains of coronavirus
or other viruses that come to infect animals making the transition to humans and resulting
in human to human spread, like SARS-CoV-2 did. Systems need to be developed for early
recognition and containment. A broader understanding and mitigation of underlying
conditions that support animal to human disease transmission are critical for prevention.
To understand our current enemy, the SARS-CoV-2 virus, manage COVID-19 disease consequences
and prepare for and hopefully prevent future zoonotic viral pandemics, we need international
multidisciplinary teams leading research to determine which characteristics of COVID-19
are universal versus mediated by local conditions of health, medical resource access,
cultural customs, and other social determinants of health. We have seen this with
our fight against HIV/AIDS through the collaborative efforts of the International
AIDS Society, established in 1988 and representing 180 countries, activities of the
WHO and the Joint United Nations Programme on HIV/AIDS (UNAIDS), and many international
nonprofit and non-governmental organizations.
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.
Where do we go from here?
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.