**2. Special populations**

#### **2.1 Pregnant and breastfeeding women**

The general approach to prevention, evaluation, diagnosis, and treatment of pregnant women with suspected COVID-19 is largely similar to that in nonpregnant individuals.

#### **2.2 Children**

Symptomatic infection in children appears to be relatively uncommon; when it occurs, it is usually mild, although severe cases have been reported.

#### **2.3 People with HIV**

The impact of HIV infection on the natural history of COVID-19 is uncertain. The clinical features appear the same as in the general population. However, many of the comorbid conditions associated with severe COVID-19 (eg, cardiovascular disease) occur frequently among persons with HIV, and it is unclear whether these or other potential confounding features, rather than HIV infection itself, contribute to the risk. Low CD4 cell count may be associated with critical illness and death in patients with HIV and COVID-19.

### **3. Oral manifestations associated with COVID-19**

Although many physicians continue to question the direct link between SARS-CoV-2 and oral disease, studies suggest that the mouth might be the most vulnerable area to this virus due to the abundance of the ACE2 (angiotensin converting enzyme) receptor in oral tissue.

The ACE2 receptor has been well-documented to be the target receptor of the SARS-CoV-2 virus and the portal of entry into the human cell. Compared with other oral tissues, cells of the salivary glands, tongue, and tonsils carry the most RNA linked to proteins that the SARS-CoV-2 virus needs to infect cells [11].

Oral manifestations associated with COVID-19 infection includes:

### **3.1 Gingival inflammation**

Bleeding and inflammation in oral tissue have been suggested to be a result of a generalized increase in inflammation due to elevated levels of cytokines and interleukins initiated by the SARS CoV-2 virus. COVID-19 disease severity has been linked to an immune dysregulation, leading to a cytokine storm. Periodontal disease can increase levels of circulating cytokines, particularly interleukin-6 (IL-6), which has been implicated as one of the major interleukins leading to the cytokine storm [12] and periodontal disease is currently being examined as a possible contributing disease toward COVID-19 severity.

#### **3.2 Xerostomia (dry mouth)**

COVID-19 has been suggested to cause dry mouth for a variety of reasons. The most common is mouth breathing by an individual due to mask use. Mouth breathing can desiccate oral tissue especially without frequent hydration. Studies suggest that another biologic mechanism involves viral entry into the salivary glands, which are known to be abundant in the ACE2 receptor [13].

#### **3.3 Oral ulcerations and gingival tissue breakdown**

COVID-19 has been associated with vascular anomalies due to viral damage of blood vessels a process whereby the virus gains entry into the endothelial cells that line blood vessels via the ACE2 receptor and damages them. Tissue necrosis, including oral ulcerations, can be the result of vessel damage. Ulceration and tissue damage can be further exacerbated by increased inflammation and upregulation in inflammatory markers due to the SARS-CoV-2 virus [14].

#### **3.4 Loss of taste and smell**

A sudden onset in loss of taste (ageusia) and smell (anosmia) are two symptoms that can be the earliest indicators of COVID-19. An average of 47% (up to 80%) of individuals who test positive for COVID-19 can have subjective complaints of taste and smell loss, particularly in cases of asymptomatic or mild disease [15]. The mechanism behind this loss is suspected to be viral disruption of cranial nerves 1, 7, 9, and 10, as well as the supporting cells of neural transmission [16]. In addition, because the tongue has an abundance of ACE2 receptors, direct viral entry into tongue cells is possible.

#### **4. Laboratory findings**

Common laboratory findings among hospitalized patients with COVID-19 include lymphopenia, elevated aminotransaminase levels, elevated lactate dehydrogenase levels, elevated inflammatory markers (eg, ferritin, C-reactive protein, and erythrocyte sedimentation rate), and abnormalities in coagulation tests. Lymphopenia is especially common, even though the total white blood cell count can vary. On admission, many patients with pneumonia have normal serum procalcitonin levels; however, in those requiring ICU care, they are more likely to be elevated. Several laboratory features, including high D-dimer levels and more severe lymphopenia, have been associated with critical illness or mortality.
