**10. COVID-19 and Gastro-intestinal involvement**

Though pulmonary manifestations such as fever and cough are the commonly reported presenting symptoms in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the presenting symptoms in other organs such as the GI tract and hepatobiliary, including nausea/vomiting and diarrhoea, were also reported [69–77]. The entry of SARS-CoV-2 in human cell is through protein ACE-2 which is found on the surface of lung alveolar epithelial cells and also on enterocytes of the small intestine [70]. One of the study of 1099 patients with COVID-19 in retrospective analysis showed that the main presenting symptoms were fever (87.9%) and cough (67.7%), followed by diarrhoea (3.7%) and vomiting (5.0%) [69]. Out of

all the GI symptoms, there was higher incidence of diarrhoea and abdominal pain present in severe COVID-19 patients than that in patients with mild COVID-19 [69]. In one of the larger studies, systematic review and meta-analysis of 35 studies on GI manifestations, consisting of 6686 patients of COVID-19infection, the three commonest symptoms include nausea and/or vomiting, diarrhoea and loss of appetite with the pooled prevalence of all GI symptoms was 15% [71].

Currently, loss of appetite was reported, ranging from 1.0% to 79% [71]. It can be explained by taste dysfunction up to some extent, which was found in as high as 88.0% in group of 417 mild-to-moderate COVID-19 patients in Europe. Also taste dysfunction almost go hand in hand with olfactory dysfunction with a high prevalence of 85.6% and may further aggravate loss of appetite as identified in the study [47, 72].

Furthermore, SARS-CoV-2 RNA was first detected in a stool specimen from the first reported COVID-19 case in the United States (US) [73]. In a study of Chinese cohort with 73 COVID-19confirmed hospitalised patients, 53.42% of the patients had detected viral RNA in the stools, after the complete clearance from the respiratory tract with undetectable viral RNA but still it had been identified in the stool specimen [74]. SARS-CoV-2 has also been detected in stool samples of the patients in one of the studies without having GI symptoms [75].

Many a times diagnosis of COVID-19 has been missed as initial presenting symptom may be involving GI tract rather than respiratory tract. Many researchers proposed that patients with GI symptoms might have a bad prognosis than those without digestive symptoms, hence clinician had to give importance to patients presenting with GI symptoms such as diarrhoea for early diagnosis [76, 77]. In the same study, rate of severity of disease was also significantly increased in patients with GI symptoms as compared with those without GI symptoms [76]. Pan and colleagues also showed the same result that as the severity of the disease increased, there is worsening of GI symptoms [77].

#### **11. COVID-19 and Skin involvement**

Skin manifestations of COVID-19 include a wide variety of skin disorders which may include specific COVID-19 related dermatoses and a variety of other skin disorders that may be worsened by COVID-19 infection [78–85]. Like other viral infections, skin rash is the most common manifestation, which is described as confluent, erythematous, morbilliform, maculopapular rash. Urticarial rash is found in one fifth of the skin manifested cases. Early lesions can be in form of vesicular eruptions which may appear before symptoms also. Pseudo-chilblain like lesions is described as late manifestation in which acral areas will have red vesicles or pustules. Livedo reticularis/racemose-like pattern can appear with COVID-19 symptoms. Purpuric "vasculitic" pattern is associated with severe COVID-19 infection [78, 79]. Acute urticaria is well known to be triggered by viral infections and COVID-19 is no exception [80]. Urticarial vasculitis has also been well demonstrated in a few patients. Urticarial vasculitis differs from urticaria and in that the lesions tend to persist beyond 24 hours and can be painful instead of pruritic [81]. Confluent maculopapular rash is also a well known manifestation of viral infections. Monomorphic vesicular exanthema is often considered an important clue to COVID-19infection. It differs from chicken pox in the fact that chicken pox rash tends to be polymorphic. Chilblain like acral pattern often manifests with cold sensitivity and purplish discoloration of the extremities. This is believed to be a manifestation of hypercoagulability and prothrombotic consequence of COVID-19. Livedo reticularis is believed to be often of similar aetiology. Purpuric lesions

are one of the most common manifestations of COVID-19. Purpuric lesions involving the heel known as "COVID-19 heel" is one the specific markers of COVID-19 infection [82–85].

The mutant strains of COVID-19 are believed to cause more extra pulmonary symptoms and thus skin manifestations of COVID-19 too could become more evident.
