Diverse clinical manifestations of the Coronavirus Disease-2019 (COVID-19)

Abstract

Since Coronavirus disease 2019 (COVID-19) was declared a pandemic by World Health Organization (WHO) in March 2020, over 240 million cases and 4.8 million deaths have been reported worldwide [1] as of October 2021. A myriad of COVID-19 clinical manifestations has been reported during the pandemic with the spectrum of the disease ranging from an asymptomatic presentation to severe respiratory failure through to multiple organ dysfunction [2]. The rising trend has been occasioned by general non-adherence to COVID-19 protocols with contribution from the diverse clinical manifestations which serves as a barrier to early diagnosis. Clinically COVID-19 has been categorized into mild, moderate, severe, and critical stages. Individuals with respiratory failure are classified as severe whereas those with acute respiratory distress syndrome (ARDS) and multiple organ dysfunction are said to be at the critical stage [3]. About a quarter to one-third of patients infected with SARS-CoV-2 are usually asymptomatic [4].

Typically, symptomatic COVID-19 patients present with clinical features suggestive of respiratory system involvement such as cough and sore throat with prodromal symptoms of fever, malaise. Acute onset of anosmia and dysgeusia in the setting of the patent nasal airway are indicative of COVID-19 and have been included in the primary screening symptoms of the disease [2,5]. These mild upper respiratory features can progress to pneumonia and respiratory failure [2]. Atypical presentations due to involvement of other organ systems such as cardiovascular, gastrointestinal, genitourinary, haematological, ophthalmic, dermatological, otorhinological and central nervous systems have also been recorded. By the diverse presentations, COVID-19 may mimic other disease conditions which may lead to a delayed or missed diagnosis. In this issue there two patients with COVID-19 presenting as appendicitis and acute pancreatitis respectively have been reported. COVID-19 clinically mimicking appendicitis has also been described in the literature [6]. Cases of acute pancreatitis caused by SARS-CoV-2 have been documented and tend to be common in those with severe disease [7]. Autopsy reports have revealed inflammation, necrosis and calcification of the pancreas in patients infected by the SARS-CoV-2 with about two-thirds of these patients manifesting clinical features of acute pancreatitis before their death [8]. The underlying pathophysiological mechanisms responsible for pancreatic damage is yet to be well established [9]. Gastrointestinal symptoms as outlined in the case report are a relatively common presentation of COVID-19 and often precede respiratory symptoms [10]. Hepatobiliary involvement also occurs with up to 50% of COVID-19 patients having abnormal liver function tests, which may be an indicator of progressive respiratory disease or may herald multiple organ failure [2,10]. Evidence of a wide array of COVID-19 manifestations due to the involvement of other major organ systems is available in the literature. These include diverse cardiac presentations from acute cardiac injury due to both ischaemic and non-ischaemic mechanisms, acute kidney injury and other features of renal dysfunction, stroke, Guillain-Barre Syndrome and other neuropsychiatric conditions resulting from damage to central and peripheral nervous systems [2,11–14]. 

The diverse manifestation of COVID-19 has been attributed to the ability of the SAR-CoV-2 virus to directly damage multiple organ tissues. This is possible due to the widespread expression of angiotensin-converting enzyme 2 (ACE2) receptors and transmembrane serine protease 2 (TMPRSS2) in multiple organ systems which enable the virus to enter target cells [15]. This leads to a cascade of signals which can induce the production of pro-inflammatory and pro-thrombotic mediators that cause tissue damage through inflammation, thrombosis, capillary leak syndrome and disseminated intravascular coagulation [16]. An exaggeration of this immune response referred to as the cytokine storm can ultimately result in ARDS and multiorgan failure [16]. Generally, the level of immune response in an infected individual is a determinant of COVID-19 outcome [3]. Other factors that indirectly mediate the variable manifestations in these patients include hypoxia, bacterial sepsis, cardiogenic shock, adverse effects of medications used, and underlying chronic conditions [2,10]. These atypical presentations may occur with or without typical respiratory manifestations and tend to be associated with critical illness and poor clinical outcomes including death [2,10,11,14]. The risk of adverse outcomes is highest among older adults and those with underlying comorbid conditions such as diabetes, hypertension, chronic kidney disease, chronic lung disease and malignancy [2]. In addition to being abreast with the various clinical manifestations of COVID-19, it is imperative that healthcare personnel also have a high index of suspicion in this era of the pandemic. Together these will prevent misdiagnosis, facilitate early diagnosis and institution of proper management including appropriate interventions to limit the spread of COVID-19. The suggestion made by authors of the case reports to perform a polymerase chain reaction test and computed tomographic scan of the chest of patients whose diagnoses are not clear is worth pursuing. Indeed, increased awareness of the diverse presentation of COVID-19 among the general population will also enable affected individuals to report early to health facilities for appropriate care..

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