In early December 2019, the first case of pneumonia of unknown origin was identified in Wuhan. As of May 17, 2020, approximately 4,710,614 cases have been reported from over a hundred countries worldwide. More than 315,023 patients have died from severe infection with this novel virus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This enveloped RNA, beta coronavirus was first identified by high-throughput sequencing. SARS-CoV-2 has a receptor-binding domain structure similar to that of SARS-CoV, as shown with the help of homology modeling [1]. Zhou et al. [2] found that 96% of SARS-CoV-2 and bat coronaviruses are similar at the whole-genome level. The clinical disease course of this highly contagious illness, known coronavirus disease 2019 (COVID-19), has not yet been well described in the medical literature. During this ongoing pandemic, the center-specific clinical experience of COVID-19 is being shared by researchers worldwide. To date, there is no effective vaccine or targeted therapy available. Therefore, supportive treatment alone is the mainstay of clinical management [3]. Subsequently, it’s proven that the virus causing COVID-19 is similar to SARS-CoV and was designated as SARS-CoV-2 [4,5]. The COVID-19 outbreak was declared a “Public Health Emergency of International Concern” by the World Health Organization (WHO) on January 30, 2020 [6]. SARS-CoV-2 is capable of human-to-human transmission, and has spread worldwide by SARS-CoV-2-infected international travelers. In this study, we explored the clinical features and related laboratory parameters of more than 3,000 cases of COVID-19 and evaluated critical factors that may affect the disease course and prognosis. This review also focuses on the COVID-19 disease course and symptoms among pregnant women, with the intent to analyze the effect of COVID-19 on the progress of pregnancy and neonatal outcomes. We also evaluated the possibilities of vertical transmission of COVID-19 infection. This analysis is critically important and discusses COVID-19 as a public health hazard to “sensitize” the policymakers, health care givers, and primary physicians.

The human coronavirus is one of the primary pathogens of respiratory infections worldwide. The 2 highly pathogenic coronaviruses, SARS-CoV and the Middle East respiratory syndrome-related coronavirus (MERS-CoV), cause severe respiratory syndrome in humans and have led to global epidemics in the past decades. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the coronavirus strain that causes a COVID-19 spread worldwide, posing a critical threat to global health. MERS-CoV is a species of coronavirus was first reported in Saudi Arabia in 2012, which is responsible for a viral respiratory disease [7,8]. In addition, 4 different human coronaviruses (HCoV) have been shown to induce mild upper respiratory disease, including HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1 [9]. Despite the high number of infections linked with COVID-19, it seems to have a lower death rate than either SARS-CoV or MERS-CoV [10-12].

The similarity of the phylogenetic profiles between SARS-CoV-2 and SARS-CoV also lead to some overlapping clinical symptoms. Certain organs are more predisposed to COVID-19 infection when compared with SARS-CoV, MERS-CoV, and seasonal influenza infections. For example, seasonal influenza is more common in respiratory outpatient clinics and wards [13-15]. There are 6 coronavirus species currently known to cause infections in humans. SARS-CoV-2 is most closely linked to SARS-CoV as they share a similar receptor, that is, angiotensin-converting enzyme receptor-2. This evidence indicates that COVID-19 may partially mimic SARS [2]. The SARS-CoV mortality has been reported as more than 10%, while MERS-CoV has been reported to be higher than 35% [16].

The global society has experienced viral epidemics in the past, such as SARS in 2003, followed by MERS in 2012. SARS and MERS were public health calamities worldwide due to high death rates of 9.6% for SARS-CoV and 34.4% for MERS-CoV globally [1,29,30]. In the current scenario of an ongoing pandemic, the knowledge and experience of clinical management acquired in the past have been a great help in countries such as Taiwan, with only 7 deaths reported till date [30]. Many single-center-based experiences with relatively low numbers of cases have been published in the medical literature on COVID-19. The current review included the latest studies from January to May 2020 to analyze the clinical characteristics of COVID-19.

This review included more than 3000 patients and reflected the most recent data since the emergence of the novel coronavirus. The median age for symptomatic cases that required hospital care was 53 years (range, 47-62 years) (Table 1). Although the disease affected all age groups, the elderly patients had a relatively severe disease course. This analysis showed that a higher proportion of infected patients were male (55.2%) compared with females (44.8%). A similar finding was shown by a recently published study on 13,184 cases, where 55% of males were affected by COVID-19 infection [31]. The same study has also emphasized that cases with severe outcomes were predominantly males in the older age group. The predisposition for infection among males could have been attributed to a smoking habit, which is usually valid for most lung-related infective and neoplastic lesions. However, our limited data showed that approximately 86% of COVID-19 cases were non-smokers. This has also been discussed by Sanchez-Ramirez and Mackey [32]; they categorically identified a significant association between COVID-19 infection and a contemporary history of respiratory disease, current smoking, and former smoking.

Initial blood-based investigations (Table 3) showed no changes in the initial hemoglobin levels, and a predominance of reduced TLC counts among 27.69% of cases, along with reduced absolute lymphocyte counts among 65.08% of cases. This is a common laboratory finding associated with any viral illness. A similar finding of lymphopenia (72.3%) and other deranged laboratory parameters was reported by Zhan et al. [33] in their cohort of 405 cases from China. A few cases (18.45%) also had mildly raised neutrophils, probably representing a secondary bacterial infection, as viral illnesses make the epithelial mucosa more prone to bacterial infections. The most common symptoms (Table 1) were fever (85.0%), cough (70.63%), fatigue (32.05%), chest tightness (37.36%), dyspnea (31.95%), shortness of breath (31.19%), and expectoration (33.27%). Fever and cough were also the most prevalent symptoms in other studies [33,34]. Minor symptoms included body myalgia (15.48%), diarrhea (11.39%), chills (10.12%), and sore throat (9.40%). Symptoms such as chest pain (5.54%), abdominal pain (3.80%), and hemoptysis (1.21%) were rarely present. These rare symptoms always have the potential to masquerade as symptoms associated with angina, with cardiac pain as the elderly population is commonly being infected. These symptoms are primarily due to a generalized response against the infection, and the predisposition of the lungs to the infection makes cough and expectoration common symptoms.

COVID-19 was commonly associated with comorbidities such as hypertension (21.60%), diabetes (9.96%), and cardiovascular disease (5.78%) (Table 2). The association of comorbidities with COVID-19 can be attributed to the general risk factor of increased infectivity among the elderly population. A recently published meta-analysis [35] of 25 studies involving 11 pre-existing comorbid conditions in 484 subjects showed that cardiovascular disease (risk ratio [RR] 2.25, 95% confidence interval=1.60-3.17, number of studies=14), hypertension (1.82 [1.43 to 2.32], n=13), diabetes (1.48 [1.02 to 2.15], n=16) were among the top comorbid conditions significantly associated with COVID-19.

Analysis of the biochemical parameters revealed high levels of raised albumin (53.72%), LDH (45.71%), and natriuretic peptide (34.84%), followed by various liver enzymes ALT (21.86%) and AST (25.33%) (Table 3). Parameters such as total bilirubin were raised among only 7.94% of the cases studied. LDH has been identified as a marker for severe prognosis in multiple diseases, including cancer and infection. In severe COVID-19 cases, the elevated LDH levels suggested that LDH may be correlated with lung damage and tissue injury [36-38]. This could indicate an overall compensatory response to the viral illness, which predominantly affects the respiratory system. Further, severe COVID-19 is associated with drastically elevated inflammatory cytokine levels, such as CRP (59.51%) and tumor necrosis factor (TNF) (58.26%). Biguenet et al. [39] confirmed that both LDH and CRP levels were elevated in the first ten days of the illness. In a few cases, ESR (57%), IL-6 (54%), IL-2 (52%), IL-10 (30%), and IL-8 (10.16%) increased with elevated prolactin levels (6.5%). Although, there is no direct evidence of an association between COVID-19 and pro-inflammatory cytokines and chemokines in lung pathology, elevated serum cytokines signify a rapid multiplication of the virus and massive inflammatory infiltrates, resulting in acute lung injury [40,41].

Symptomatic management was the mainstay of treatment, and more than 50% of cases required a combination of oxygen therapy (58.26%), antiviral therapy (57.97%), and antibiotics (50.35%) (Table 4). Combinations of antiviral and antibiotic therapies were utilized to prevent secondary bacterial infections and further deterioration of the illness. The cases in our study had common complications related to cardiac injuries (27.69%), followed by ARDS (23.06%). A few cases of acute renal injury (6.76%) and septic shock (4.15%), and occasional cases of DIC (1.60%) were also noted. In a study conducted in China, acute cardiac injury was the most common complication, with most cases dying between 2-19 days after admission to the ICU [42]. The treatment responses and associated comorbidities affected the duration of hospital stay and mortality. The overall mortality rate was about 172/2,621 (6.56%), and the hospital recovery rate was approximately 41.89%. The figures appear to represent the initial pandemic intervention in the most affected areas of the Asia Pacific region. However, in another study, a total of 17 deaths were reported from a meta-analysis of 12,258 cases in the United States of America [43]. This difference can be attributed to many factors such as clinical symptoms, smoking status, age, and other associated comorbid conditions. Other factors could be the ethnicity, time and sudden load of epidemic cases, available infrastructure, calamity preparedness, and so on. The countries that were not affected in the initial pandemic wave had some crucial period for preparedness and are expected to be relatively better in overall outcome figures.

Maternal and neonatal outcomes in COVID-19: Clinical and laboratory characteristics of COVID-19 among pregnant women were analyzed from 4 published retrospective studies (Table 5). The most common symptoms were fever (53.50%) and cough (35.41%), followed by malaise (19.46%) and shortness of breath (13.58%). The findings showed no difference in the frequency and characteristics of clinical symptoms between pregnant and non-pregnant women. Other published studies have reported similar findings [44,45]. Another published meta-analysis [46] of 28 studies on 11,432 pregnant women suggested that symptoms such as fever and myalgia were less frequently reported than in age-matched non-pregnant women, and pregnant women were more likely to need hospital admission. In addition to clinical features, other minor symptoms such as nausea and vomiting have been reported in non-pregnant women, but overlooked by pregnant women, probably because these symptoms are usually present throughout pregnancy. Laboratory parameters such as decreased TLC (80.20%) and lymphocytes count (44.30%), and elevated CRP levels (50.73%), have also been reported in another study on 1,316 pregnant women, where lymphocytopenia and high CRP levels were observed in 55-100% of cases. The majority of the women were on antiviral and antibiotic therapy, along with oxygenation therapy support. In relatively later published studies [47], data related to hydroxyl-chloroquine (79.7%) treatment have also been reported.

Most of the pregnancies had a gestational age of 28-41 weeks, and underwent an institutional cesarean section delivery (77.07%). This is probably because most of the studies were from the referral hospital identified for COVID-19 management. A preterm delivery rate of 28.10% was observed in our study. A similar study from Ethiopia on pregnant women reported a preterm birth rate of 14.3% [46]. The findings related to APGAR score at 1 minute and 5 minutes after birth were within the normal range. The study also observed that the incidence of COVID-19 among newborn neonates was 25/665 (3.75%). A total of 60/186 (32.25%) neonates were transferred to neonatal intensive care. The odds of preterm birth were higher in COVID-19 infected pregnant women than in non-infected pregnant women [47]. Most studies [44,45,48] have reported good APGAR scores along with events such as fetal distress, miscarriage, respiratory distress, and preterm delivery in pregnant women. COVID-19 infection was evaluated in maternal blood, cord blood, amniotic fluid, and breast milk; all of the studies [43,45,48] reported no evidence of vertical transmission. The rate of infection of 3.1% among neonates in our study can probably be attributed to environmental exposure after birth. Overall, clinical and laboratory characteristics were similar in both pregnant and non-pregnant women.

The major limitation of this review is the geographic location; however, it could not be avoided as it coincided with the epicenter of COVID-19 infection. The selection of studies published in English also limits our review, as we may be missing some vital information published in the local languages. The selection bias for studies with a larger number of clinical and laboratory parameters might have resulted in the loss of vital information in smaller case series and reports. The pandemic is still ongoing; however, since it erupted in the Asia-Pacific region, the outcome will be based on region-specific clinical and data management.

This review summarizes the clinical and laboratory parameters of COVID-19 patients, which would enable primary physicians and health care givers to provide an early and definitive diagnosis for an accelerated response. The primary objective for this in-depth analysis is to learn about common and less common signs and symptoms in normal as well as pregnant women. There is also the need to understand symptoms that might masquerade as pre-existing physiological conditions such as pregnancy or associated comorbidities. This may facilitate administrative policymakers and public health experts to deliver health policy-related decisions based on existing knowledge.