Novel Coronavirus (COVID-19): Risk Factors, Cytokine Storms, and Testing

Novel Coronavirus (COVID-19): Risk Factors, Cytokine Storms, and Testing

Friday, March 27, 2020

As of March 27, 2020, there have been 588,861 confirmed coronavirus disease 2019 (COVID-19) cases, with 26,928 people succumbing to the virus and 132,440 patients recovered1. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has an estimated case fatality rate of 2-3%, with increased fatality rates for immunocompromised and elderly populations.2

COVID-19 patients can show an array of symptoms ranging from mild to moderate respiratory issues, such as dry coughing, to very serious infections leading to respiratory distress accompanied by pneumonia.3 Additionally, viral loads detected in asymptomatic patients were similar to symptomatic patients, suggesting transmission of the virus is possible regardless of the presence of symptoms.3

In another study, performed by Kelvin To and colleagues, researchers investigated the viral load and antibody profiles for 23 COVID-19 positive patients. Their findings showed the following:

  • At ~1 week, viral loads peaked
  • At ~2 weeks, viral loads gradually declined
  • There was a correlation between age and viral load
  • IgG and IgM antibodies began increasing at ~ day 10
  • IgG and IgM antibody level against the SARS-CoV-2 internal nucleoprotein and the surface spike receptor-binding domain correlated with neutralizing activity

These findings not only confirm the contagious nature of asymptomatic patients but help to explain SARS-CoV-2 high rates of transmissibility.4 Furthermore, these findings are aligned with other reports of early-stage transmission of infection and have helped direct public health policy to follow social distancing initiatives.

Pre-Existing Conditions that Increase the Risk of SARS-CoV-2

SARS-CoV-2 binds to host cells via angiotensin-converting enzyme 2 (ACE2).5 The expression of ACE2 is increased for individuals who have type I and II diabetes as treatment options include ACE inhibitors and ARBs. Additionally, hypertension, which is treated with ACE inhibitors and ARBs, also results in increased expression of ACE2.5 The increase in ACE2 receptors from hypertension medications, and diabetes medications is the basis of the initial hypotheses that suggest ACE2 upregulation may explain the correlation between these conditions. However, there is certainly not a consensus on these conclusions, with other evidence contradicting these claims to show that ACE2 protects patients from severe acute lung failure.6 The only known is that there is a correlation between severity of COVID-19 cases and patients with hypertension, diabetes, and obesity. More research is needed to establish an explanation of these correlations at this time.

The COVID-19 Cytokine Storm

Cytokines, small proteins that function as a means of signaling and communication between cells, have a variety of functions within the body. Among their diverse responsibilities, they play a key role in immune and inflammatory responses. The cytokines associated with a COVID-19 cytokine storm include increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumor necrosis factor-α.7 As localized inflammation increases, systemic circulation begins to spread it throughout the body. In patients with COVID-19, infections have resulted in respiratory infections and systemic sepsis compounding in severity as a cascade of detrimental secondary infections emerge. Genetics are certainly implicated in the degree to which patients become vulnerable to cytokine storms.8 To learn more regarding effective treatment strategies regarding cytokine storms in severe influenza cases, select here.

Testing Strategy and Kit Availability

SARS-CoV-2 and SARS-CoV-2 antibody testing strategies have differed between countries. Additionally, timelines of testing, population testing strategy and control mechanisms to reduce viral infection rates have been influenced by each countries resources and sociopolitical structure. The United States has committed several of its states to shelter in place directives, while other states have yet to implement these isolation strategies. The balancing act between viral containment and economic viability has begun in nations all over the globe.

Testing strategies share the same degree of country-based variability. For instance, the United States maintains a stay at home directive, even when mild to moderate symptoms manifest unless a high-grade fever begins. Whereas countries like South Korea, as of March 19, have conducted the highest per capita testing strategy in the world with more than 307,000 tests.9

Iceland and the Netherlands are beginning to screen large portions of its population for antibodies to determine what percent of the population has developed immunity and how long immunity is maintained.10

The following companies have released a notice of either COVID-19, SARS-CoV-2, SARS-CoV-2 antibody testing equipment, and kits:

  • Abbott Laboratories
  • AMSBIO
  • Bio-Rad
  • Hamilton Company
  • Henry Schein, Inc
  • Impact Health
  • Millipore Sigma
  • PerkinElmer
  • Premier Medical Laboratory
  • RayBiotech
  • Scanwell Health
  • SmartPharm
  • Sorrento Therapeutics

As information regarding infection rates and risks begins to build, one universal understanding that the scientific community agrees on is limit your contact with others. The necessity to decrease the rate of infection cannot be emphasized enough. In doing so, you will help ease the burden of health care professionals, protect vulnerable populations and increase the global fight against the SARS-CoV-2 pandemic.

References:

  1. “COVID-19 Coronavirus Pandemic: Coronavirus Cases”. March 27, 2020. https://www.worldometers.info/coronavirus/
  2. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020; (published online Feb 24.) DOI:10.1001/jama.2020.2648
  3. Zou L, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med 2020; 382:1177-1179. DOI 10.1056/ (published online March 19.) https://www.nejm.org/doi/full/10.1056/NEJMc2001737
  4. KK-W, Tsang OT-Y, Leung W-S et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020; (published online March 23.) https://doi.org/10.1016/S1473-3099(20)30196-1
  5. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J Virology. 2020; (published online Jan 29.) DOI:10.1128/JVI.00127-20
  6. Imai, Y., Kuba, K., Rao, S. et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 436, 112–116 (2005). https://doi.org/10.1038/nature03712
  7. Huang C, Wang Y, Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395: 497-506
  8. Tisoncik, Jennifer R et al. “Into the Eye of the Cytokine Storm.” Microbiology and molecular biology reviews: MMBR vol. 76,1 (2012): 16-32. doi:10.1128/MMBR.05015-11
  9. Bedingfield, Will. “What the world can learn from South Korea’s coronavirus strategy”. Published online March 21, 2020. https://www.wired.co.uk/article/south-korea-coronavirus
  10. Barber, Gregory. “Researchers Push for Mass Blood Tests as a Covid-19 Strategy. Published online March 25, 2020. https://www.wired.com/story/researchers-push-for-mass-blood-tests-as-a-covid-19-strategy/

 

 

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