How Do Novel Coronaviruses Affect Human Health?

by İTÜ | Mar 09, 2020
The outbreak of COVID-19 caused by the coronavirus named 2019-nCoV spread from Wuhan, China, influenced the world.

The outbreak of COVID-19 caused by the coronavirus named 2019-nCoV spread from Wuhan, China, influenced the world. We talked to Assoc. Prof. Dr. Ceren Çıracı Muğan from the department of Molecular Biology and Genetics of Istanbul Technical University regarding the impact of coronavirus on human health.

In 2019, an outbreak started in the city of Wuhan, China, and still continues in March 2020. As of March 4, it has infected over 90,000 people globally11. Due to the contagiousness, lack of efficient treatment and mortality rate of coronavirus, extensive government action including compulsory quarantines are being implemented as the coronavirus knows no borders. Internationally, countries have limited travel to and from affected areas and have implemented scanning actions to be able to detect potential carriers of the virus.

We discussed the human health perspective of coronavirus (corona, meaning crown in Latin) infection with Assoc. Prof. Dr. Ceren Çıracı Muğan from the department of Molecular Biology and Genetics, who focuses her research on the understanding the mechanism of actions of immune responses from a host standpoint.

Could you define the family of Coronaviruses?

Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The name coronavirus originates from the Latin corona, meaning "crown" which refers to the morphology of the virus particles. Coronaviruses are a family of viruses that are widespread in different species of animals such as cats, cattle, camels and bats. Animal coronaviruses can rarely infect people and spread between people such as Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV). This recently emerged virus is called the novel (new) coronavirus 2019 (2019-nCoV) and the disease that 2019-nCoV causes is called COVID-191-3.

The genome size of coronaviruses ranges from 26000 to 32000 bases and considered the largest amongst the previously discovered RNA viruses. The genome of 2019-nCoV was sequenced quickly during the outbreak. The genetic sequence analysis indicated that the 2019-nCoV is within the β-coronavirus genus, with a 79 % nucleotide identity to SARS-CoV and 51.8% identity to MERS-CoV. Morever, 2019-nCoV is 96% identical across the entire genome to a bat coronavirus. Inoculation of the 2019-nCoV onto surface layers of human airway epithelial cells in vitro resulted in cytopathic effects and stopped cilium beating of the cells4. The cilium is crucial to keep the airways clear of mucus and dirt, therefore allowing us to breath easily.

What are the source and spread of the COVID-19?

We know the viruses circulate in a range of animals, sometimes these viruses can make the jump from animals to humans and this is called a “spillover”. It could be due to range of many factors such as mutations in the virus or increased contact between humans and animals. Tens of thousands of cases of COVID-19 have been reported to be spreading from person to person in parts of the country by health officials of China. Most of the reported cases are associated with travel from Wuhan, now also are being reported in an increasing number of international locations, including the United States. The sequences from U.S. patients are similar to the one that China initially announced, suggesting a likely single, recent emergence of this virus from an animal reservoir. Many of the infected individuals had some link to a large seafood and live animal market, indicating animal-to-person spread. Later, a growing number of infected people reportedly did not have exposure to animal markets, suggesting person-to-person spread1-3.

Viruses can infect all living things whose cell(s) have the right receptor for the virus entry. 2019-nCoV infected people by binding human angiotensin-converting enzyme (ACE2), resulting severe pneumonia and high mortality rate in patients. ACE2 is found on the surface of vascular endothelial cells, mostly on those of the lungs7. ACE2 plays an important role in the renin–angiotensin system (RAS) which is a hormone system that regulates blood pressure and fluid and electrolyte balance, as well as systemic vascular resistance6. Animal studies noted that RAS inhibitors might efficiently ease the symptoms of acute severe pneumonia and respiratory failure. Interestingly the binding of 2019-nCoV to ACE2 resulted in the exhaustion of ACE2 and the balance of the RAS system was destroyed, which could result in the worsening of acute severe pneumonia. Thus, it could be speculated that ACEI and AT1R inhibitors could be used in patients with pneumonia when blood pressure is under control and they might even reduce the pulmonary inflammation and mortality11.

Although this may not be the main way the virus spreads, 2019-nCoV contaminated surfaces or objects can possibly infect people as well, if they touch their mouth, nose or even eyes.

What we know about the diagnostic testing and treatment of COVID-19?

The ongoing research on 2019-nCoV has enhanced the development of new diagnostic tools; a real-time RT-PCR diagnostic test specific for 2019-nCoV is now avaliable. The test kit is called “Centers for Disease Control and Prevention (CDC) 2019-Novel Coronavirus (2019-nCoV) Real-Time Reverse Transcriptase (RT)-PCR Diagnostic Panel.” It is compatible with the Applied Biosystems 7500 Fast DX Real-Time PCR Instrument with SDS 1.4 software. This test is aimed for use with upper and lower respiratory specimens from people who meet CDC criteria for 2019-nCoV testing. CDC’s test kit is suggested to be used by qualified laboratories in the United States. The test kits also is shipped to qualified international laboratories, such as World Health Organization (WHO) Global Influenza Surveillance Response System (GISRS) laboratories2. 2019-nCoV RNA has been detected in blood and stool specimens, upper respiratory tract specimens and bronchoalveolar lavage fluid, but whether infectious virus is present in extrapulmonary specimens remains to be determined2.

Re-analyzation of the computational data and findings reported in two recent manuscripts by Ji et al., 2020 and by Pradhan et al., 2020 suggested that snakes are the intermediate hosts of 2019-nCoV and the 2019-nCoV spike protein insertions shared a similarity to HIV-18,9. However, another study by Zhang et al, 2020, relying on larger-scale datasets and utilizing the most up to date bioinformatics approaches and databases, arrived a different conclusion than Ji et al and Pradhan et al, which the latter was retracted later on. Based on Zhang et al’s analyses and currently avaliable data of coronaviruses, they concluded that the intermediate hosts of 2019-nCoV are likely to be mammals and birds than snakes, and the new insertions detected in the spike protein are naturally evolved from bat coronaviruses10.

There is no specific antiviral drug for 2019-nCoV licensed by the U.S. Food and Drug Administration (FDA) to treat 2019-nCoV infection. Vaccine development for these type of viruses may not be that easy. Antibodies against the viral surface proteins can be generated, however, these antibodies won’t be efficient when the virus got another mutation. Therefore, further research into the pathogenesis of human coronavirus infection is a must for identifying appropriate therapeutic targets. People infected with 2019-nCoV should receive supportive care to relieve symptoms. For severe cases, treatment should support vital organ functions.  People who suspect they may have been exposed to 2019-nCoV should immediately contact their healthcare provider1,2.

Death toll passed 3200, according to the official sources12. What is the severity of COVID-19?

The whole clinical picture of 2019-nCoV is not completely understood. Reported illnesses have ranged from mild to severe, including death as a result of septic shock or other reasons. However, asymptomatic infection with 2019-nCoV have also been reported. The available data are currently not enough to identify risk factors for severe clinical outcomes. From the limited 2019-nCoV data in hand, and the data from related coronaviruses such as SARS-CoV and MERS-CoV, it is not hard to guess that older adults, and individuals who have chronic medical conditions, such as immunocompromising conditions, may be at greater risk for more severe outcomes. 2019-nCoV RNA might be detectable in the upper or lower respiratory tract for weeks after illness onset, just like the infections with MERS-CoV and SARS-CoV. However, detection of viral RNA does not necessarily point out the presence of infectious virus. Current literature on the 2019-nCoV and other relevant coronaviruses (MERS-CoV, SARS-CoV) suggest that the incubation period for the infection to occur may range from 2–14 days1-3.

There is a battle between host and virus. The race is not given to the swift nor the battle to the strong but to those who endure. The mortality rate is approximately 2% and this rate is higher for men (2.8%) than for women (1.7%)12. Patients with severe symptoms go to hospital anyways, and there is still 98% survival rate for them. I strongly believe that the immune system has a very important role in winning over the pathogen in general, therefore we need to strengthen it.

Symptoms may appear in as few as 2 days or as long as 14 days and sometimes even longer than 2 weeks after exposure and can include fever, cough and shortness of breath. How to keep yourself safe from new coronavirus and the COVID-19 ilness?

World Health Organization (WHO), Turkish Republic Ministry of Health General Directorate of Public Health13 and National Health Commision of People’s Rebuplic of China (NHC of PRC) 1 advise on the following points to keep ourselves safe.

•        Wearing masks properly is one of the effective ways to protect from getting infected

•        If you are not feeling well or have symptoms such as fever, fatique, cough and shortness of breath, a mask is also needed to prevent you from spreading viruses to others

•        Cover your cough and sneeze with tissue paper or cough into your sleeve, but avoid covering with your hands directly

•        Wash your hands frequently and properly, wash your hands with soap and running water thoroughly for at least 20 seconds, after returning home, touching trash or garbage, contacting with animals and handling animal wastes

•        Strengthen your immune system and exercise regularly

•        Regular exercise is one the most important ways to help you stay away from catching any infections

•        Make sure that shared spaces have good air flow and avoid going to crowded places such as hospitals, railways stations and airports. Wear a mask if transport or movement is necessary.

•        Seek prompt medical attention if you have symptoms of fever and respiratory infections

•        Avoid close contact with people who have flu or cold-like symptoms

•        Eat thoroughly cooked meat and eggs. Avoid contact with wild animals or farmed livestock without any protection

About Assoc. Prof. Dr. Ceren Çıracı Muğan

Ceren Ciraci received her PhD from Iowa State University and completed her postdoctoral studies at the University of Iowa Inflammation Program. She is currently an associate professor in the molecular biology department at Istanbul Technical University. Dr Ciraci has an interest in innate and adaptive immunity, in particular the study of Nod-like Receptors (NLRs). Her lab currently focuses on the regulation of adaptive immune responses through the components of innate immunity based on the preliminary results that utilized in vivo mouse models of airway inflammation.

 

References:

  1. International health commision of Republic of China (http://en.nhc.gov.cn/)
  2. Center for disease control (cdc.gov)
  3. The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (2019-NCOV ) - China CCDC, February 17 2020
  4. Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., Niu, P., Zhan, F., Ma, X., Wang, D., Xu, W., Wu, G., Gao, G.F., Tan, W., 2020. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. https://doi.org/10.1056/nejmoa2001017
  5. International Committee on Taxonomy of Viruses (24 August 2010). "ICTV Master Species List 2009 – v10”
  6. Fountain, J.H., Lappin, S.L., 2018. Physiology, Renin Angiotensin System, StatPearls.
  7. Golan, D.E., Armstrong, E.J., Armstrong, A.W., Tashjian, A.H., 2012. Principles of pharmacology: The pathophysiologic basis of drug therapy: Third edition, Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy: Third Edition.
  8. Ji, W., Wang, W., Zhao, X., Zai, J., Li, X., 2020. Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross‐species transmission from snake to human. J. Med. Virol. https://doi.org/10.1002/jmv.25682
  9.  Pradhan, P., Pandey, A.K., Mishra, A., Gupta, P., Tripathi, P.K., Menon, M.B., Gomes, J., Vivekanandan, P., Kundu, B., 2020. Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag. bioRxiv. https://doi.org/10.1101/2020.01.30.927871
  10.  Zhang, C., Zheng, W., Huang, X., Bell, E.W., Zhou, X., Zhang, Y., 2020. Protein structure and sequence re-analysis of 2019-nCoV genome does not indicate snakes as its intermediate host or the unique similarity between its spike protein insertions and HIV-1. bioRxiv. https://doi.org/10.1101/2020.02.04.933135
  11. Sun ML, Yang JMSun YP, Su GH.2020. Inhibitors of RAS Might Be a Good Choice for the Therapy of 2019-NCOV  Pneumonia. oi: 10.3760/cma.j.issn.1001-0939.2020.0014. [Epub ahead of print]
  12.  https://www.worldometers.info/coronavirus/
  13. https://hsgm.saglik.gov.tr/tr/bulasici-hastaliklar/2019-n-cov.html