An overview of the SARS outbreak
SARS, a viral respiratory disease, is a member of the Coronaviridae virus family that infects mammals and human beings.
The disease was first identified in November 2002 in the Guangdong province of southern China. It causes flu-like symptoms including fever, fatigue, headache, chills, diarrhoea and breathing difficulties, which can turn fatal in severe cases.
The incubation period is usually two to seven days after infection. In some cases, however, it may take up to ten days for symptoms to appear.
The airborne virus primarily transmits through small droplets of saliva coughed or sneezed by an infected person. It can also spread indirectly if an infected person touches surfaces with unwashed hands.
An overview of the MERS outbreak
MERS, a viral respiratory infection, is also caused by a member of the Coronaviridae family of viruses.
The first case was identified in Saudi Arabia, however, retrospective investigations have shown that the first case of MERS occurred in Jordan.
MERS spreads through the infected person’s respiratory secretions through coughing and can also transmit from animals to humans. Most of the people infected with MERS had respiratory issues and complained about shortness of breath. Other symptoms included fever and cough, while some suffered from pneumonia and kidney failure.
The median incubation period for secondary cases associated with limited human-to-human transmission is around five days.
Less than 200 MERS cases were identified in the first 18 months since the first identification, indicating that the virus is less contagious compared to SARS.
Response to the outbreak
SARS control and containment measures
The absence of pharmaceutical interventions made it imperative to ensure early detection and implementation of isolation policies to contain the outbreak. The key steps included establishing an operational authority and an incident management structure to respond to the outbreak.
The authorities focused on developing tools to identify and isolate all SARS patients and emphasised on contact tracing to prevent further SARS-CoV transmission. Clinicians and public health workers were also trained to facilitate early detection and for the implementation of new guidelines for reporting new cases.
Furthermore, screening measures were deployed for travellers coming from SARS-affected areas to mitigate transmission risks. Several infection control measures were also implemented at healthcare facilities to contain the outbreak.
MERS control and containment measures
MERS was less contagious compared to SARS, but strict infection control procedures and protocols were implemented in hospitals to limit the spread of the disease. Special emphasis was placed on delivering PPE kits to the healthcare workers and ensure basic health logistics at responding faculties.
The authorities also issued guidelines so that people exhibiting symptoms of respiratory infection follow cough etiquette, respiratory hygiene and wear masks. A restriction was also placed on movement of camels.
Recent travellers returning from the Middle East with respiratory issues were tested for MERS-CoV. However, the World Health Organization (WHO) did not advise the deployment of special screening at entry points or trade restrictions during the outbreak.
Furthermore, healthcare professionals were provided with necessary training for respiratory protection device and PPE use.
SARS vs MERS vs COVID-19: Disease and outbreak comparison
The first case of SARS was reported on 16 November 2002 and the WHO issued a global alert regarding the outbreak on 12 March 2003. The first cases in the US and Europe was reported on 19 March 2003.
A total of 8,437 suspected, probable, and confirmed cases and 813 deaths were reported. The disease had a mortality rate of 9.6%.
WHO announced on 5 July 2003 that the SARS outbreak was contained. The SARS outbreak affected 29 countries, with China, Hong Kong, Taiwan and Canada reporting maximum number of cases.
The first case was reported in Saudi Arabia on 16 September 2012. A total of 2,494 suspected, probable, and confirmed cases and 858 deaths were reported.
MERS had a mortality rate of 34%. The disease affected 27 countries, with most of the cases reported from Saudi Arabia.
The first case of atypical pneumonia was reported by Chinese state media on 31 December 2019. The virus was named SARS-CoV-2 and the disease was named COVID-19 on 11 February 2020.
The WHO declared COVID-19 as a pandemic on 11 March 2020. The mortality rate for the disease is around 1%-3%, although the exact rate yet to be ascertained.
Pharmaceutical industry response to SARS and MERS
Several pharmaceutical companies started the development of vaccines and related therapeutics following the SARS and MERS outbreaks. Most of the candidates for SARS, however, did not enter the trial phase as the outbreak was contained quickly. Some of the agents, however, are still being evaluated for MERS.
Roughly 20 vaccine candidates for SARS and MERS entered developmental stage following the outbreak. The initial enthusiasm was shown by both small biotechs as well as major leaders in vaccine development. However, most of candidates never entered the clinic as interest plummeted after the outbreaks were contained.
Further, around 40 therapies were being developed for SARS and MERS including small molecules, therapeutic antibodies and combinations of antibodies. The quick containment of the SARS outbreak and sporadic recurrences of MERS restricted pharmaceutical companies’ ability to evaluate the efficacy of the therapies.
Developments and Conclusions
Early-phase vaccines and therapeutics for SARS/MERS
There are no approved vaccines or therapeutic options for either diseases currently. The developers did not see the need for testing interventions for SARS as a recurrence was unlikely.
MERS, which persists with a very low incidence rate, made the development of vaccines equally challenging. Some of the MERS vaccine candidates and therapeutics, however, entered trial phase.
Inovio Pharmaceuticals’ INO-4301 and N.F. Gamaleya Scientific Research Institute of Epidemiology and Microbiology’s MERS vaccine entered Phase I/II phase (ongoing), according to GlobalData, Pharma Intelligence Center. The Phase I trials of Vaccitech’s VTP-500 vaccine for MERS are also underway.
The Phase I trials of Regeneron Pharmaceuticals’ REGN-3048 and REGN-3051 therapeutics have been completed. SAB Biotherapeutics has also completed Phase I testing of SAB-301.
Current and future of SARS/MERS management
The chances that a potential vaccine for SARS/MERS will be introduced in the market is extremely low due to low developer interest. The successful control of SARS outbreak and rare incidences of MERS made it extremely difficult for the developers to run trials and seek approval for any pipeline candidate.
Such challenges in the path of vaccine development also limited financial opportunities associated with developing vaccines. The future development will have to be driven by the public sector as the private sector lacks enthusiasm due to low likelihood of a meaningful financial return.
Lessons learned and implications for COVID-19
Rapid response ability
The SARS/MERS outbreaks have demonstrated the capabilities and the enthusiasm of the drug development industry to start the rapid development of prophylactic and therapeutic interventions. Around 60 vaccine candidates and therapeutic agents entered development, but nearly all of them failed to reach the market.
The industry exhibited similar readiness and in two months of the virus discovery more than a hundred preventive and treatment agents entered developmental stage, during the ongoing COVID-19 pandemic.
Development must be rapid
The developers focused on novel agents, a process which may take years to complete, during the SARS outbreak. The experience demonstrated the need to focus on platforms, which will help in accelerating the development of vaccines or therapeutics.
The adoption of this strategy was evident during the COVID-19 pandemic. Several COVID-19 candidates were either mRNA or DNA vaccines to enable rapid development. Moderna’s vaccine candidate, for example, entered Phase I studies around three months after receiving the genetic sequence of the virus.
Focus on profitability
The previous experiences have shown that the enthusiasm for the development of vaccines fade as soon as the outbreaks are controlled. Further, the sporadic incidence did not trigger enough interest on part of the developers.
As COVID-19 continues to spread unabated, the vaccine development is unlikely to face similar difficulties and the financial opportunity will keep the companies engrossed. The number of interested developers, however, is likely to drop once effective vaccines and therapeutics become available.