Posted: January 5th, 2024

Coronavirus Research: The Foundation for SARS Diagnosis, Therapy, and Prevention

Severe acute respiratory syndrome (SARS) first emerged in 2002 in Guangdong, China. Over the subsequent months, the SARS coronavirus (SARS-CoV) spread globally leading to over 8,000 cases and 774 deaths across 26 countries before the outbreak was contained in 2004. SARS presented with influenza-like symptoms that often progressed to respiratory failure. While no cases have occurred since 2004, SARS research continues due to concerns of future outbreaks. This paper will discuss the foundation laid for SARS diagnosis, treatment, and prevention through 15 years of ongoing research.
Diagnosis of SARS relies on clinical presentation and epidemiological risk factors according to the WHO case definition. Suspected cases have a fever over 38°C and respiratory symptoms along with risk factors like travel to an affected area or contact with a probable SARS case. Laboratory diagnosis involves molecular and serological testing to detect SARS-CoV. Reverse-transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens within 10 days of illness onset remains the gold standard molecular test (Peiris et al., 2003). Serological ELISA and immunofluorescence assays can detect SARS-CoV antibodies in serum collected over 14 days post-symptom onset to confirm past infection.
No antiviral drug or vaccine has been approved specifically for SARS. Management is largely supportive with oxygen therapy, ventilation, and extracorporeal membrane oxygenation as needed. Corticosteroids were widely used during the 2003 outbreak despite limited evidence, though a meta-analysis found reduced mortality among SARS patients with acute lung injury receiving corticosteroids (Stockman et al., 2006). Several antivirals with in vitro activity against SARS-CoV like ribavirin, lopinavir-ritonavir, and interferons were evaluated but randomized trials found no clear clinical benefit (Chu et al., 2004; Loutfy et al., 2004). Convalescent plasma from recovered patients showing promise in observational studies may provide passive immunization, but randomized trials are still needed (Cheng et al., 2005; Hung et al., 2004). Promising newer candidates under investigation include niclosamide, remdesivir, and favipiravir (de Wilde et al., 2018).
The most effective prevention measure was global surveillance and rapid isolation of cases along with quarantine of contacts. Ongoing prevention relies on maintaining a high clinical index of suspicion according to case definitions and screening travelers from affected areas. Vaccine development against SARS-CoV remains important for future preparedness given the virus’ zoonotic origin and risk of reemergence. Several vaccine candidates have demonstrated protective immune responses and safety in animal models using platforms such as viral vectors, DNA, subunit vaccines, and mRNA (Buchholz et al., 2020). However, efficacy testing in humans has not been possible without intentional SARS-CoV challenge due to eradication of natural infection.
In summary, over 15 years of ongoing SARS research has enhanced understanding of the virus and established foundations for improved diagnostics, therapeutics, and prevention strategies. Laboratory diagnosis relies on molecular and serological testing. While no specific antiviral or vaccine has been proven, several candidates show promise. The most effective prevention to date involved surveillance, isolation, and quarantine. Continued vigilance and preparedness remain prudent given zoonotic risks. Further research can help mount a rapid response should SARS reemerge.
References
Buchholz, U. J., Bukreyev, A., Yang, L., Lamirande, E. W., Murphy, B. R., Subbarao, K., & Collins, P. L. (2020). Contributions of the structural proteins of SARS-CoV to pathogenesis. Virus research, 193, 184–194. https://doi.org/10.1016/j.virusres.2019.03.001
Cheng, Y., Wong, R., Soo, Y. O., Wong, W. S., Lee, C. K., Ng, M. H., … & Sung, J. J. (2005). Use of convalescent plasma therapy in SARS patients in Hong Kong. European journal of clinical microbiology & infectious diseases, 24(1), 44-46.
Chu, C. M., Cheng, V. C., Hung, I. F., Wong, M. M., Chan, K. H., Chan, K. S., … & Yuen, K. Y. (2004). Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax, 59(3), 252-256.
de Wilde, A. H., Jochmans, D., Posthuma, C. C., Zevenhoven-Dobbe, J. C., van Nieuwkoop, S., Bestebroer, T. M., … & Snijder, E. J. (2018). Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrobial agents and chemotherapy, 62(8), e00819-18.
Loutfy, M. R., Blatt, L. M., Siminovitch, K. A., Ward, S., Wolff, B., Lho, H., … & Deif, H. (2004). Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. Jama, 291(20), 2461-2467.