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dcyphr | Coronavirus disease 2019 (COVID-19): current status and future perspectives

Abstract 

Much research on COVID-19 is needed to understand its nature (i.e., how it spreads) and to come up with more targets for vaccines and medication. This study discusses what is currently known about the structure and qualities of SARS-CoV-2, including how it spreads and where it comes from.  


Introduction

SARS-CoV-2 belongs to the Betacoronavirus (β-CoVs) genera of the Orthocoronavirinae subfamily, making it known to infect mammals and similar to the previous SARS-CoV and MERS-CoV. COVID-19 has spread to 72 countries and affected hundreds of thousands of people worldwide, designating it as an international health concern. There are currently no existing cures, vaccines, or specific medications for it, so research and an accurate understanding of the virus are crucial. 

Structure of SARS-CoV-2

The SARS-CoV-2 genome (the complete set of genes in a cell) encodes a polyprotein that is then cleaved and broken down into amino acids via enzymes, creating, among other proteins, the spike (S) surface glycoprotein -a structural protein. This protein is important in the attachment of SARS-CoV-2 to host cells. Thus, comprehending the structure and function of this protein may help in generating antibody drugs that ultimately contribute to developing future vaccines. 

Etiology and pathogenesis of SARS-CoV-2

SARS-CoV-2, like SARS-CoV and MERS-CoV, causes atypical pneumonia, which can be explained by humans having dipeptidyl peptidase 4 (DPP4) and angiotensin-converting enzyme 2 (ACE2) receptors in the respiratory tract. The SARS-CoV-2 surface spike (S) glycoprotein binds to these receptors well. Moreover, unlike SARS-COV, SARS-CoV-2 spike proteins bind to human ACE2 receptors 10-20x better, allowing it to spread easier. Once in the lungs, SARS-CoV-2 reproduces quickly, triggering a powerful immune response that can result in cytokine storms and lung tissue damage. Cytokine storms are key causes of acute respiratory distress syndrome (ARDS) and multiple organ failure, making it part of an especially poor presentation of COVID-19 infection. Furthermore, after SARS-CoV-2 infection patients are left with fewer and weaker T-cells, which contribute to weakened and lessened immune function. All of these contribute to lung/breathing failure in SARS-CoV-2 patients. 

Epidemiological characteristics of SARS-CoV-2

Origins of SARS-CoV-2

Many studies suggest that bats may be the natural host and pangolins may be the intermediate host for SARS-CoV-2. The first source of and whether the virus is transmitted directly from bats or via pangolin still needs to be investigated. Finding out the source will help to understand how the virus spreads and help stymie the outbreak. 


Transmission route of SARS-CoV-2

SARS-CoV-2 is transmitted between people by respiratory droplets that come into contact with one’s eyes, mouth, or nose. It may also be transmitted through aerosol in closed environments with little airflow. Some studies have suggested that it may travel through the digestive tract. Whether SARS-CoV-2 can be transmitted to babies via breastfeeding requires more research.


Susceptible population

There is an overall general susceptibility to catching COVID-19, but populations of particular concern are the elderly, those with weakened immune systems, pregnant women, and newborns. 


Incubation period

The average incubation period for SARS-CoV-2 patients is 3-7 days, revealing a substantial time period in which the disease can be transmitted. Asymptomatic patients can also spread the disease. Research supports the recommendation of surveilling patients for 14 days. 


Basic reproduction number (R0) of SARS-COV-2

Reproduction number represented as R0, or R naught, is a measure of how many susceptible people an infected patient will likely infect (i.e., R0 of measles=15). The average R0 of SARS-CoV-2 is about 3.28. 


Clinical presentation

The main early symptoms of COVID-19 are fever, fatigue, dry cough, muscle pain, and labored breathing. Other less common symptoms include headache, runny nose, sore throat, stuffy nose, vomiting, and diarrhea. Particularly bad patients usually showcase labored breathing and/or particularly low levels of oxygen in their blood after a week of infection. After this would come septic shock (organ failure and severely low blood pressure),  acute respiratory syndrome, an over-accumulation of acid in the body, and problems with the body dealing with blood clotting. 


Pathological characteristics

Pathological characteristics of SARS-CoV-2 were found to be related to acute respiratory syndrome as well as very similar to those seen in SARS-CoV and MERS-CoV. 


Computed tomography (CT) imaging characteristics

CT is helpful when patients present with a persistent cough, fever, and fatigue. CT imaging also supports the devastating effects SARS-CoV-2 has on the lungs. 


Detection of SARS-CoV-2

Using reverse transcription-quantitative PCR (RT-qPCR) or viral gene sequencing of nasopharyngeal swabs, stool, or blood samples, scientists are able to detect the nucleic acid of SARS-CoV-2. Studies have shown that saliva samples may be effective and less invasive to collect for SARS-CoV-2 detection. CRISPR-based SHERLOCK (Specific High-sensitivity Enzymatic Reporter UnLOCKing) technique uses synthetic SARS-CoV-2 RNA fragments for COVID-19 detection. This technique is quicker and more accurate than RT-qPCR, so it will likely be used with clinical patients. 

Treatments 

General treatments

Patients should be in a safe and comfortable environment in which food and water are not an issue, and vital signs are actively monitored. They should also be kept away from others to keep the disease from spreading. 


Antiviral therapy

Interferon-alpha (IFNα) has been shown to directly interfere with and inhibit viral replication as well as help immune responses. Lopinavir/ritonavir (Kaletra) has been shown to help severe patients of SARS or MERS by improving acute respiratory syndrome. It may also inhibit the protein synthesis of SARS-CoV-2. Ribavirin can thwart RNA and DNA replication of viruses by stopping inosine monophosphate dehydrogenase activity. Chloroquine is a cheap and safe drug that has been shown to effectively stop SARS-CoV-2 in vitro. Arbidol is shown to similarly stop the reproduction of COVID-19 in vitro. Remdesivir has been reported to obstruct SARS-CoV and MERS-CoV in vivo (in a living organism). 


Cellular therapy 

Human Natural Killer (NK) cells are immune cells that break down the membrane of antibody-coated virus-infected cells by the process of antibody-dependent cellular cytotoxicity (ADCC). NK cell therapy can enhance immunity and is currently viewed as a viable strategy for treating and preventing pneumonia from SARS-CoV-2. 

Mesenchymal stem cells (MSCs) have been shown to effectively treat acute respiratory syndrome and reduce lung fibrosis, designating it as a favorable therapy for COVID-19 patients. 


Immunotherapy 

Convalescent plasma (plasma removed from the blood of a recovered patient) therapy has been used for previous infection diseases like Ebola and may effectively treat SARS-CoV-2 patients. Monoclonal antibodies may be important to SARS-COV-2 remission. The monoclonal antibody CR3022 targets the 193-amino acid receptor binding domain (RBD) of the spike protein of SARS-CoV-2 without overlapping with the ACE2 binding site. Thus, this monoclonal antibody has potential for treating COVID-19 pneumonia by itself or with other monoclonal antibodies.


Chinese medicine

Glycyrrhizin, hesperetin, baicalin, and quercetin are Chinese medicines that may help with preventing and treating COVID-19 pneumonia. 

Conclusion & future directions

COVID-19 affects the lungs, liver, gastrointestinal organs (i.e., small intestine), esophagus, testis, and kidney. Its characteristics and ease with which it infects humans make designing therapies, drugs, and vaccines imperative. Research may have to focus on establishing animal models that summarize various aspects of human disease and vaccines.