As COVID-19 Unfolds: What We Know And Where Are We Headed!
About Coronaviruses: Coronaviruses are enveloped +ve sense RNA viruses, with spike like projections on their surface giving them crown like appearance under the electron microscope; hence the name coronavirus, they range from 60 nm-140 nm in diameter. Four genera found: α, β (α& β descend from gene bat pool), γ and δ.
History of human diseases with Coronaviruses: Four coronaviruses including HKU1, NL63, 229E and OC43 have been in circulation amongst humans, and generally cause mild respiratory diseases. In the past two decades, there has been two events wherein crossover of animal beta-corona viruses to humans has resulted in severe disease:
- 2002– 2003: SARS (Severe Acute Respiratory syndrome) a new coronavirus of the β genera and with origin in bats crossed over to humans via the intermediary host of palm civet cats in the Guangdong province of China later designated as affected – people and – deaths.
- 2012: MERS- Cov (the Middle East respiratory syndrome coronavirus), of bat origin, emerged in Saudi Arabia with dromedary camels as the intermediate host and affected 2494 people and caused 858 deaths (fatality rate 34 percent).
Origin of COVID-19: COVID 19 or SARSCoV-2 is a β coronavirus of group 2B and whole genome sequencing has revealed that it has >95 percent homology with the bat coronavirus, >80 percent identity to SARSCoV and >50 percent to MERS-CoV. Many of the initial COVID-19 cases in Wuhan had common exposure to Huanan sea food market. COVID-19 was identified as a coronavirus that environmental samples from the Huanan seafood market tested positive, signifying that the virus originated from there. Although, it is known that the COVID-19 originated from bats, the intermediary animal through which it crossed over to humans is uncertain (snakes, minks and pangolins are the current suspects).
Pathogenesis and Epidemiology: Studies have identified angiotensin-converting enzyme 2 (ACE2) as the entry receptor for this virus. Ongoing studies for finding therapies targeting binding of the virus to ACE2 receptor seems to be promising.
Although elderly people and people with pre-existing conditions are more vulnerable to become severely ill, people from all ages are susceptible, and it is estimated that one in four coronavirus carriers can be asymptomatic. Infection is transmitted through large droplets generated during coughing and sneezing by symptomatic and asymptomatic patients.
Studies have shown higher viral loads in the nasal cavity as compared to the throat. Patients can be infectious for as long as the symptoms last and even while on clinical recovery. The infected droplets can spread one to two millimeters and deposit on surfaces. The virus can remain viable on surfaces for days in favorable atmospheric conditions but are destroyed in less than a minute by common disinfectants including hydrogen peroxide. Infection is acquired either by inhalation of these droplets or touching surfaces contaminated by them and then touching the nose, mouth and eyes. Since, the virus is also present in the stool and contamination of the water supply and subsequent transmission via aerosolization/ feco oral route is also hypothesized. Currently, transplacental transmission from pregnant women to their fetus has not been described but neonatal disease due to post-natal transmission is possible.
Clinical features: The incubation period of the virus is about 14 days and duration of viral shedding varies from 10 days to up to 37 days. The clinical features of COVID-19 are indistinguishable from other respiratory infections including fever (not in all), cough, sore throat, headache, fatigue, headache varies and ranges from asymptomatic state to acute respiratory distress syndrome and multi organ dysfunction. An increase in inflammatory cytokines including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα has been reported with the progression of disease which might be responsible for organ dysfunction. Loss of smell and taste has also been reported in some cases.
According to the CDC, there are 89 verified laboratories using COVID-19 diagnostic tests, including at least one laboratory in all 50 states, along with Guam and Puerto Rico. The diagnosis due to limited capacity precludes testing all patients with suspected COVID-19. In the United States, the Centers for Disease Control and Prevention (CDC) and the Infectious Diseases Society of America have suggested priorities for testing, high priority testing being given to the most critically ill patients and symptomatic healthcare individuals.
- Real-time reverse transcription polymerase chain reaction (rRT-PCR) on respiratory samples is the standard method for testing COVID-19.
- Recently, Abbott has received emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) for the fastest available molecular point-of-care test for the detection of novel coronavirus (COVID-19), delivering positive results in as little as five minutes and negative results in 13 minutes. This test uses isothermal nucleic acid amplification technology instead of PCR and hence does not rely on time consuming series of alternative temperatures of PCR.
- Around the world, there has been efforts to develop blood and serological/antibody tests (detecting IgM and IgG antibodies by ELISA) as diagnostic tools.
Immunity: Although, there are reports of protective antibodies found in the infected individual, itis unknown whether all infected patients mount a protective immune response and how long the protective effect lasts. Neutralizing activity in plasma of recovered patients has been identified.
- Treatment is essentially supportive and asymptomatic
- Patients with severe disease often need oxygenation support
- Transfusion with convalescent plasma has shown promising results. Critically ill patients when received convalescent plasma that has COVID-19 neutralizing activity from the recovered patients, showed improvement.
Investigational approaches/ Potential therapies:
- Convalescent plasma with neutralizing activity
- TMPRSS2 inhibitors: Drugs including camostat, a protease inhibitor may be able to block the viral entry process. Clinical trials are currently undergoing
- Chloroquine and hydroxychloroquine: An anti-malarial drug, hydroxychloroquine has been administered to hospitalized COVID-19 patients and several clinical trials in USA to test its efficiency are underway.
- Lopinavir-ritonavir: did not show promising results with hospitalized COVID-19 patients with pneumonia
- Remdesivir: An anti-viral, adenosine analogue, which incorporates into nascent viral RNA chains and causes their pre-mature termination. Multiple clinical trials are underway to evaluate its efficacy and safety.
- Anti-Ace2 antibodies: Might be able to prevent viral entry in the cells by blocking the receptor.
Potential Vaccines: Unfortunately, there are no current vaccines for COVID-19 but there have been extensive studies carried out globally to find one. Some recent studies have shown promising results:
- Studies by Kim et al showed that the mice that received SARS-CoV-2 subunit vaccines delivered by microneedle array, showed potent virus-specific IgG antibody responses.
- BCG vaccine and COVID-19: In the past, there has been reports of nontargeted protective effect of BCG vaccine against lower respiratory infection. There have been some studies which are investigating whether BCG vaccine can protect against COVID-19.
Cheng, Z. J., & Shan, J. (2020). 2019 Novel coronavirus: where we are and what we know. Infection, 1-9.
Kim, E., Erdos, G., Huang, S., Kenniston, T. W., Balmert, S. C., Carey, C. D., … & Korkmaz, E. (2020). Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development. EBioMedicine, 102743.
Lisa Maragakis (2020) coronavirus-test-what-you-need-to-know, John Hopkins medicine.
McIntosh, K., Hirsch, M. S., & Bloom, A. (2020). Coronavirus disease 2019 (COVID-19). Hirsch MS, Bloom A (Eds.). Accessed Mar5.
Miller, A., Reandelar, M. J., Fasciglione, K., Roumenova, V., Li, Y., & Otazu, G. H. (2020). Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. medRxiv.
New, B. D., & Newswire, P. R. Fully Automated BD Phoenix CPO Detect Test Receives FDA Clearance.
Rothan, H. A., & Byrareddy, S. N. (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity, 102433.
Singhal, T. (2020). A Review of Coronavirus Disease-2019 (COVID-19). The Indian Journal of Pediatrics, 1-6.
World Health Organization. (2020). Laboratory testing of 2019 novel coronavirus ( 2019-nCoV) in suspected human cases: interim guidance, 17 January 2020.
Zhou, P., Yang, X. L., Wang, X. G., Hu, B., Zhang, L., Zhang, W., … & Chen, H. D. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579 (7798), 270-273.
About the Author
Manpreet Semwal is a student in the Molecular Immunology & Microbiology discipline of the Integrated Biomedical Sciences program. Her research focuses on addressing the physiological functions of Reactive oxygen species (ROS) in stromal cells in the young, steady state thymus. She is working in Dr. Ann Griffith’s lab that focuses on identifying the causes and consequences of age-associated thymic stromal dysfunction. Their ultimate goal is to develop novel approaches to extend the health span during aging. Read more about her work in the article, “Manpreet Semwal: Having a Ph.D. Will Help Me Train Future Scientists.”
The “Beyond The Bench” series features articles written by students and postdoctoral fellows at the Graduate School of Biomedical Sciences at The University of Texas Health Science Center San Antonio.