Are oral manifestations related to SARS-CoV-2 mediated hemolysis and anemia?

COVID-19 has displayed heterogeneity in the clinical manifestations ranging from asymptomatic state to life treating severe acute respiratory distress syndrome. Gustatory impairment (45%) in the form of dysgeusia (38%), hypogeusia (35%) and ageusia (24%) are the most common manifestation followed by the mucosal erythema or ulcerations [1]. Apart from these two, literature also reported anosmia as one of the most common manifestations of COVID-19 [2]. Majority of the patients showed only gustatory and olfactory manifestations without any evidence of respiratory symptoms [2]. Many hypotheses have been proposed to envisage oral manifestations seen in COVID-19 patients but none has been tested and proved with appropriate scientific experimentations. A brief overview of proposed pathogenesis is reflected in Table 1 [4], [5], [6], [7]. In the present letter, we proposed a novel hypothesis that links the SARS-CoV-2 with anemia and oral manifestations.

Table 1

Proposed hypotheses for the oral manifestations in COVID-19 patients.

Authors	Year	Pathology	Proposed Hypothesis
Finsterer and Stollberger [3]	2020	Gustatory manifestations	Local inflammatory response resulting from rhinitis hampers the normal function of taste buds.
Finsterer and Stollberger [3]	2020	Gustatory manifestations	Direct interaction of SARS-CoV-2 with gustatory components and ACE2 receptors.
Vaira, Salzano, Fois, et al. [4]	2020	Gustatory manifestations	SARS-CoV-2 may bind essential salivary mucin components, such as sialic acid, consequently accelerating taste particle degradation and disturbing gustatory sensation
Nataf [5]	2020	Gustatory manifestations	ACE2 interaction with SARSCoV-2 may affect normal gustatory functions through dopamine and serotonin synthesis pathway co-regulation.
Mariz et al. [6]	2020	Gustatory manifestations	Inability of ACE2 to degrade Angiotensin II protein during COVID-19 infection, resulting in disorderly taste responses.
Galván Casas et al. [7]	2020	Mucosal ulcers	Not a primary manifestation of SARSCoV-2 but secondary manifestation related to co-infections from bacterial and viruses
Current hypothesis	2020	Gustatory manifestations and mucosal ulcers	Anemia related to SARS-CoV-2 mediated hemolysis causes the oral manifestations.

Hypothesis: Anemia related to SARS-CoV-2 mediated hemolysis causes the oral manifestations.

ACE2, CD147, and CD26 receptors present on the erythrocytes are potential targets for SARS-CoV-2 attachment, which can lead to hemolysis [8]. Moreover, SARS-CoV-2 may mimic the action of hepcidin, which increases circulating and tissue ferritin leading to serum iron deficiency and anemia [8]. In support of this contention, significantly higher number of COVID-19 patients demonstrated severe anemia and hyperferritenemia [9], [10].

Intriguingly, gustatory impairment and mucosal ulcerations including anosmia are the prime manifestations of iron deficiency anemia [11]. These manifestations are results of the impaired oxygen supply and related cellular atrophy in the taste buds, oral epithelium and olfactory epithelium. Thus, we strongly believe that pathogenesis for oral manifestations seen in COVID-19 could be related to SARS-CoV-2 induced anemia. Burning sensation of oral cavity, canker sores and pale oral mucosa are other manifestations associated with iron deficiency anemia and they should also be investigated in COVID-19 patients. We believe that they could be missed out due to mild nature of these symptoms or unawareness among the healthcare workers.

To prove the proposition, a correlative study of total iron binding capacity or hemoglobin level and oral manifestations is warranted in COVID-19 patients. If this proposition holds true then it will help in effective management of oral health of COVID-19 patients.

Funding source

The author received no specific funding for this work.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.