CLINICAL PATHOLOGY OF SARS-CoV-2 (COVID-19)
The disease caused by SARS-CoV-2 is also named severe specific contagious pneumonia (SSCP), Wuhan pneumonia, and, recently, COVID-19 (110). Compared to SARS-CoV, SARS-CoV-2 has less severe pathogenesis but has superior transmission capability, as evidenced by the rapidly increasing number of COVID-19 cases (111). The incubation period of SARS-CoV-2 in familial clusters was found to be 3 to 6 days (112). The mean incubation period of COVID-19 was found to be 6.4 days, ranging from 2.1 to 11.1 days (113). Among an early affected group of 425 patients, 59 years was the median age, of which more males were affected (114). Similar to SARS and MERS, the severity of this nCoV is high in age groups above 50 years (2, 115). Symptoms of COVID-19 include fever, cough, myalgia or fatigue, and, less commonly, headache, hemoptysis, and diarrhea (116, 282). Compared to the SARS-CoV-2-infected patients in Wuhan during the initial stages of the outbreak, only mild symptoms were noticed in those patients that are infected by human-to-human transmission (14).
The initial trends suggested that the mortality associated with COVID-19 was less than that of previous outbreaks of SARS (101). The updates obtained from countries like China, Japan, Thailand, and South Korea indicated that the COVID-19 patients had relatively mild manifestations compared to those with SARS and MERS (4). Regardless of the coronavirus type, immune cells, like mast cells, that are present in the submucosa of the respiratory tract and nasal cavity are considered the primary barrier against this virus (92). Advanced in-depth analysis of the genome has identified 380 amino acid substitutions between the amino acid sequences of SARS-CoV-2 and the SARS/SARS-like coronaviruses. These differences in the amino acid sequences might have contributed to the difference in the pathogenic divergence of SARS-CoV-2 (16). Further research is required to evaluate the possible differences in tropism, pathogenesis, and transmission of this novel agent associated with this change in the amino acid sequence. With the current outbreak of COVID-19, there is an expectancy of a significant increase in the number of published studies about this emerging coronavirus, as occurred with SARS and MERS (117).
SARS-CoV-2 invades the lung parenchyma, resulting in severe interstitial inflammation of the lungs. This is evident on computed tomography (CT) images as ground-glass opacity in the lungs. This lesion initially involves a single lobe but later expands to multiple lung lobes (118). The histological assessment of lung biopsy samples obtained from COVID-19-infected patients revealed diffuse alveolar damage, cellular fibromyxoid exudates, hyaline membrane formation, and desquamation of pneumocytes, indicative of acute respiratory distress syndrome (119). It was also found that the SARS-CoV-2-infected patients often have lymphocytopenia with or without leukocyte abnormalities. The degree of lymphocytopenia gives an idea about disease prognosis, as it is found to be positively correlated with disease severity (118). Pregnant women are considered to have a higher risk of getting infected by COVID-19. The coronaviruses can cause adverse outcomes for the fetus, such as intrauterine growth restriction, spontaneous abortion, preterm delivery, and perinatal death.
Nevertheless, the possibility of intrauterine maternal-fetal transmission (vertical transmission) of CoVs is low and was not seen during either the SARS- or MERS-CoV outbreak (120). However, there has been concern regarding the impact of SARS-CoV-2/COVID-19 on pregnancy. Researchers have mentioned the probability of in utero transmission of novel SARS-CoV-2 from COVID-19-infected mothers to their neonates in China based upon the rise in IgM and IgG antibody levels and cytokine values in the blood obtained from newborn infants immediately postbirth; however, RT-PCR failed to confirm the presence of SARS-CoV-2 genetic material in the infants (283). Recent studies show that at least in some cases, preterm delivery and its consequences are associated with the virus. Nonetheless, some cases have raised doubts for the likelihood of vertical transmission (240–243).
COVID-19 infection was associated with pneumonia, and some developed acute respiratory distress syndrome (ARDS). The blood biochemistry indexes, such as albumin, lactate dehydrogenase, C-reactive protein, lymphocytes (percent), and neutrophils (percent) give an idea about the disease severity in COVID-19 infection (121). During COVID-19, patients may present leukocytosis, leukopenia with lymphopenia (244), hypoalbuminemia, and an increase of lactate dehydrogenase, aspartate transaminase, alanine aminotransferase, bilirubin, and, especially, D-dimer (244). Middle-aged and elderly patients with primary chronic diseases, especially high blood pressure and diabetes, were found to be more susceptible to respiratory failure and, therefore, had poorer prognoses. Providing respiratory support at early stages improved the disease prognosis and facilitated recovery (18). The ARDS in COVID-19 is due to the occurrence of cytokine storms that results in exaggerated immune response, immune regulatory network imbalance, and, finally, multiple-organ failure (122). In addition to the exaggerated inflammatory response seen in patients with COVID-19 pneumonia, the bile duct epithelial cell-derived hepatocytes upregulate ACE2 expression in liver tissue by compensatory proliferation that might result in hepatic tissue injury (123).