COVID-19: History
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Contributor:
Yung-Fang Tu
,
Chian-Shiu Chien
,
Aliaksandr A. Yarmishyn
,
Yi-Ying Lin
,
Yung-Hung Luo
,
Yi-Tsung Lin
,
Wei-Yi Lai
,
De-Ming Yang
,
Shih-Jie Chou
,
Yi-Ping Yang
,
Mong-Lien Wang
,
Shih-Hwa Chiou
,
skills technology
,
Yang I. Pachankis

We present an overview of the current state of knowledge on the SARS-CoV-2 and COVID-19 pandemic. In addition to an overview of the epidemiological, clinical, and radiological features of SARS-CoV-2, we also summarize possible therapeutic options currently under investigation and the future outlook for the disease. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic. The current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis. Further on, regression analytical review is presented on the virological and evolutionary history of SARS-CoV viruses.

  • COVID-19
  • SARS-CoV-2
  • pneumonia
  • ACE2
  • clinical trials

1. General Clinical Features of COVID-19

The usual symptoms of COVID-19 include fever (83–98%), cough (59–82%), shortness of breath (19–55%), and muscle ache (11–44%), which are similar to those of SARS and MERS. [1] Some patients may have sore throat, rhinorrhea, headache and confusion a few days before the onset of fever, indicating that fever is a critical symptom, but not the only initial manifestation of infection. [1] The pattern of fever has not yet been fully understood. A small proportion of patients had hemoptysis [2][3], and a number of cases were found relatively asymptomatic. [4] COVID-19 patients may have normal or lower white blood cell counts, lymphopenia, or thrombocytopenia, with the increased C-reactive protein level. [1][2][3] People who have fever and upper respiratory tract symptoms with leukopenia or lymphopenia should be suspected for this disease, especially for patients with travel history to the endemic area or close exposure record.

However, the clinical course of COVID-19 pneumonia exhibits a broad spectrum of severity and progression patterns. In some patients, dyspnea develops within a median of 8 days after the onset of illness (range of 5–13 days), while in others, respiratory distress may be absent. [2] Around 3–29% patients may need the admission to the intensive care unit. Severely ill patients may have poor disease course of rapid progression to multiple organ dysfunction and even death [1][2], and those who have shortness of breath and hypoxemia can quickly progress into acute respiratory distress syndrome (ARDS), severe sepsis with shock, and even multiple organ dysfunction within one week. [3][5] ARDS was observed to develop in 17–29% of hospitalized patients approximately 8 days after symptoms onset, and the global mortality rate reached approximately 5.4% [2].

It is also worth noting that the gastrointestinal symptoms of COVID-19 may be caused by the direct viral damage to the intestine rather than the immunopathogenic response to the lung infection of the host. Since angiotensin-converting enzyme 2 (ACE2), the main cellular receptor of SARS-CoV-2 is expressed in the human gastrointestinal epithelial cells, it is believed that the viral shedding at the gastrointestinal tract and fecal–oral transmission is highly plausible. [6] Indeed, it was reported that the rectal swabs showed positive results even after the nasopharyngeal tests were constitutively negative [7]. Besides, the live virus was also detected in stool samples of diseased patients. This evidence strongly indicate that stool can be contagious for a long time after the discharge of patients based on two negative nasopharyngeal swabs. Thus, adding rectal swabs to the discharge criteria should be considered for the prevention of both nosocomial and community spread of COVID-19.

Aside from the gastrointestinal symptoms, a retrospective study of 214 patients in China reported that 5.6 % of patients experienced hypogeusia and 5.1 % experienced hyposmia [8]. Though the loss of olfaction during SARS-CoV-2 infection could be explained by the swelling of the nasal mucosa, a larger population of patients should be included to determine whether hypogeusia and hyposmia could be a common neurological manifestation of COVID-19. Nevertheless, hyposmia and hypogeusia are now being recommended as the early warning signs and an indication for early self-isolation.

2. Radiological Features of COVID-19

The radiological examinations, including chest X-ray (CXR) and chest computed tomography (CT) scan, are important for early detection and treatment of COVID-19 [9]. The imaging findings of COVID-19 pneumonia mimic influenza, SARS-CoV, and MERS-CoV pneumonia [10][11][12][13][14]. The primary Wuhan study revealed that upon diagnosis, 74 [75%] patients showed bilateral pneumonia, and the remaining 25 [25%] patients showed unilateral pneumonia. [1] In addition, 14 [14%] patients showed multiple mottling and ground-glass opacities [1]. In the subsequent study, it was reported that the predominant pattern of abnormality observed was peripheral (44 [54%]), ill-defined (66 [81%]), and mainly involved the right lower lobes (225 [27%] of 849 affected segments) [1]. Bilateral multiple consolidation usually occurs in more severe cases [9].

Chest CT is more efficient in detecting pneumonia at the early stages of COVID-19. However, the imaging findings of COVID-19 pneumonia on chest CT are variable and nonspecific [15][16][17]. The most common patterns of COVID-19 on chest CT scans include multiple GGO lesions (56.4%), and bilateral patchy shadowing (51.8%), and the other patterns consist of local patchy shadowing (28.1%), and interstitial abnormalities (4.4%). Severe cases tend to yield more prominent radiologic findings on chest CT scan, such as more bilateral patchy shadowing (82%), more multiple GGO lesions (60%), and more local patchy shadowing (55.1%) than non-severe cases. No CXR or chest CT abnormality was identified in 17.9% of non-severe cases and 2.9% of severe cases [1][2][18]. Pure GGO lesions can be found in the early stages. Focal or multifocal GGO lesions may progress into consolidation or GGO lesions with superimposed interlobular/intralobular septal thickening as crazy-paving pattern during disease progression, and the expansion of consolidation represented disease progression [19][19][19]. Pure consolidative lesions were relatively less common. Pulmonary cavitary lesion, pleural effusion, and lymphadenopathy are rarely reported [20][21][19][22].

However, interestingly, it was also reported that asymptomatic patients could show early CT changes [23]. Conversely, as mentioned earlier, another study has shown positive RT-PCR results for SARS-CoV-2 in the absence of CT changes [24]. Despite the limited number of cases available for thorough radiographic study, we can observe the trend of varied presentations of COVID-19 pneumonia. Asymptomatic patients showing positive CT findings undoubtedly pose challenges for the current diagnostic protocol, especially those patients who have false-negative RT-PCR results.

Moreover, different radiographic patterns are seen as the COVID-19 progresses. Typically, after the first to second week of the onset, lesions progress to bilateral diffused pattern with consolidations. By contrast, both ground-glass opacification and consolidation were present relatively early in SARS [5]. This again could be indicative of the significant difference in diagnostic sensitivity between these two diseases, especially at early or asymptomatic stage. In conclusion, correlating imaging features with clinical and laboratory findings to assess patients may be essential to facilitate early diagnosis of COVID-19 pneumonia (Figure 1).

Ijms 21 02657 g001 550

Figure 1. Overview of symptomatic, radiological and laboratory characteristics of COVID-19.

Comparison between Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2

Whereas several human coronaviruses that cause mild respiratory diseases, such as HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, were estimated to circulate in the human population for centuries, SARS-CoV, MERS-CoV, and SARS-CoV-2 were zoonotically transferred from other mammalian species in the last 20 years [11][12][13][14]. Horseshoe bats are the natural reservoirs of these novel coronaviruses, and the intermediate hosts that transmitted the virus to the human were identified to be the masked palm civet for SARS-CoV, and dromedary camel for MERS-CoV (Table 1). The recent metagenomics study has detected the most similar coronaviruses to SARS-CoV-2 in the Malayan pangolin (Manis javanica), one of the species presumably smuggled to the Huanan wet market in Wuhan [25].

Table 1. Comparison of the epidemiological, clinical and radiological features of the diseases caused by SARS-CoV, MERS-CoV, and SARS-CoV-2.

  SARS-CoV MERS-CoV SARS-CoV-2
Disease SARS MERS COVID-19
Transmission
  • Respiratory droplets
  • Close contact with diseased patients
  • Fecal-oral
  • Aerosol [26]
  • Respiratory droplets
  • Close contact with diseased patients/camels
  • Ingestion of camel milk
  • Respiratory droplets
  • Close contact with diseased patients
  • Possibly fecal-oral [6]
  • Possibly aerosol [27]
Latency 2–7 days 2–14 days 97.5% became symptomatic within 11.5 days (CI, 8.2 to 15.6 days) [28]
Contagious period 10 days after onset of disease When virus could be isolated from infected patients Unknown
Reservoir Bats Bats Bats
Incidental host Masked palm civets Dromedary camels Malayan pangolin [29]
Origin Guangdong, China Saudi Arabia Hubei, China
Fatality rate ~10% ~36% ~2.3%
Radiologic features Diverse from focal faint patchy ground-glass opacities to bilateral ill-defined air space consolidations on plain chest radiograph. Non-specific to distinguish between three different diseases. Ref. [30][31][32][33]
Clinical presentation From asymptomatic or mild disease to acute upper respiratory distress and multiorgan failure leading to death. Varies between individuals. Ref. [34]
Vomiting and diarrhea are also reported.

The difference in the transmission patterns between SARS-CoV, MERS-CoV, and SARS-CoV-2 is also indicative of the specific intrinsic characteristics of SARS-CoV-2 [11]. In the case of SARS-CoV and MERS-CoV, substantial virus shedding happens only after the onset of symptoms, therefore, the transmission mainly occurs in a nosocomial manner, namely, after the infected patients have sought medical help [35]. However, human-to-human transmission of SARS-CoV-2 occurs predominantly in communities and between family members, which might indicate that the pathogen could be spread far before the onset of symptoms. A recent study suggested that the half-lives of SARS-CoV-2 and SARS-CoV were similar in aerosols with the median infectious period estimated to be around 1.1 to 1.2 hour [27]. Therefore, as an echo to SARS-CoV, the possibility of air-borne and fecal–oral transmission of SARS-CoV-2 cannot be ruled out, however, more evidence is still needed.

In addition to the pre-existing factors that contribute to the blind spot of disease control, previous studies found that during active surveillance, two individuals with close contact history with confirmed cases showed positive results on RT-PCR. Another report revealed patients that had been proven to recover from COVID-19 by two consecutive RT-PCR tests, turned out to show positive results a few days later. While the patients continued to be asymptomatic and no people within their close contact were infected, they were still considered as infectious viral carriers [24].

In conclusion, the evidence exists that the infected cases can be contagious before the onset and after treatment of COVID-19 pneumonia. Thus, current criteria for hospital discharge and discontinuation of quarantine may have to be reevaluated in order to achieve a more intact protocol for adequate disease control. Table 1 compares different features of SARS-CoV, MERS-CoV, and SARS-CoV-2.

2. Virological Features

Even though SARS-CoV viruses are popularly believed to be a form of respiratory syndrome, by which it was named, evidence exists that there is a structural similarity between HIV-1 gp41 and SARS-CoV Spike 2 proteins [36]. This feature in fusion peptide continues to mutate in SARS-CoV-2 and its variants [37][38]. Further questions have been raised on the categorical rationale on the virological features of SARS-CoV series that it is too over-lengthed for single-strand virus, and corresponds better to the negative-sense paramyxovirus [39].

This entry is adapted from the peer-reviewed paper 10.3390/ijms21072657

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