Emerging Infectious Diseases
Coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most infected individuals develop mild to moderate illness and recover without hospitalisation, although some proportion may go on to experience mid- and long-term effects, commonly referred to as ‘long COVID’. Symptoms of acute infection are variable but often include fever, cough, fatigue, and the distinctive loss of taste or smell. The elderly and those with multiple underlying medical conditions are at the greatest risk of severe disease, which can be fatal without medical intervention. As the virus is transmitted by aerosols, public health infection prevention and control measures are important. Most of these measures continue to be employed globally under more relaxed guidelines, alongside mass vaccination campaigns to prevent infection and/or severe illness.
SARS-CoV-2 was first identified in Wuhan, China in December 2019. The WHO declared the outbreak a Public Health Emergency of International Concern (PHEIC), WHO’s highest warning level, on 30 January 2020. As of mid-June 2022, there have been 535 million confirmed cases and 6.3 million deaths globally, though the true death toll is estimated to be more than double that due to under-reporting.
The emergence of virus variants associated with increased transmission and/or disease severity spurred the assessment and classification of variants of interest (VOI) and variants of concern (VOC). The Omicron variant and its sub-lineages remain a concern, partly due to its ability to reinfect those with either vaccine- or infection-derived immunity. The ability for variants to cause reinfection challenges herd immunity, shifting the focus of mass vaccination to booster doses and potentially seasonal immunisation.
As of April 2022, there were 35 vaccines approved for use by at least one national regulatory authority, ten of which have WHO Emergency Use Listing. Under the WHO’s recently-revised Target Product Profile (TPP), a need remains for vaccines which confer protection against severe disease for at least one year, and are active against other coronaviruses and/or potential future variants. Other key attributes of the TPP address LMIC needs, such as non-parenteral administration, higher thermostability, lower frequency of booster doses, and potential coadministration with other vaccines.
There is a need for therapeutics to reduce mortality in hospitalised symptomatic patients with COVID-19, including pregnant women and children under six; preferably a daily oral dose, or a short-course parenteral or inhaled therapy for those requiring ventilation. Only two antivirals have received WHO prequalification – Pfizer’s Paxlovid (nirmatrelvir/ritonavir) and Gilead Sciences’ Veklury (remdesivir) – both of which are for patients at high risk of hospitalisation. The WHO also conditionally recommends the use of the antiviral molnupiravir developed by MSD (Merck) and two monoclonal antibody therapies – Regeneron’s REGEN-COV (casirivimab/imdevimab) and GSK’s Xevudy (sotrovimab) – early in cases where there is elevated risk of severe disease or hospitalisation.
Two diagnostic TPPs remain unmet: point-of-care tests for prior infection with SAR-CoV-2, and test for prior infection with SAR-CoV-2 suitable for analysing a moderate to high volume of samples. Molecular diagnosis of SARS-CoV-2 is recommended by the WHO and is considered the gold standard for case confirmation. However, it is complicated, costly, and slow to execute and not readily accessible in low-resource settings. As of April 2022, 28 in vitro diagnostics have received WHO Emergency Use Listing, six of which are rapid antigen tests. Though less sensitive, antigen-detecting rapid diagnostic tests are quicker, cheaper and can be used outside of clinical and laboratory settings.
SK bioscience and GSK are seeking approval for their recombinant protein-based SKYCovione vaccine candidate with GSK pandemic adjuvant, after Phase III trials demonstrated its superiority to AstraZeneca’s Vaxzevria, one of the most widely used vaccines; they plan to make the vaccine available through COVAX for equitable access. Veru Inc. has applied for US FDA Emergency Use Authorization for sabizabulin, an anti-inflammatory and antiviral drug to treat hospitalised patients at high risk of acute respiratory distress syndrome – a patient group for which there are no antivirals currently recommended for use – following Phase III trials which demonstrated a 55% reduction in mortality.