A urine mass spectrometry-based same-day diagnostic test for COVID 19

COVID-19 due to SARS-CoV-2 has evolved into a global pandemic, surpassing over a million deaths world-wide during September 2020. Diagnosis in the acute phase is based on detection of genomic material using RT-PCR. However, RT-PCR, though a same-day test, has several drawbacks. These include: (i) False negative rate of between 20 and 40% in the early phase of the disease, (ii) the need for kits and reagents to perform RNA extraction, and the reverse transcription and PCR steps, and, (iii) an appreciable infection control risk posed to healthcare workers because nasopharyngeal swabbing is an aerosol generating procedure. Furthermore, detection of the virus by RT-PCR provides no information on likely disease prognosis or organ specificity. These drawbacks, including the cumbersome nature of the assays, has resulted in severe testing backlogs. In many parts of South Africa turnaround times increased to between 5 and 10 days. The testing strategy and criteria was subsequently altered to reduce the turnaround time. This resulted in many undiagnosed cases. Thus, alternative and additional testing capacity is urgently required. To address these shortcomings, we propose the development of a mass spectrometrybased same-day test for COVID-19 using urine. Urine represents the filtrate of whole blood and, in line with other diseases, would be expected to contain viral genomic material and proteins (though whole virus is not readily culturable from the urine). Our preliminary data support this hypothesis and mass spectrometry testing of a limited number of samples has revealed that COVID-19 is characterised by a distinct urine signature that can be rapidly identified by mass spectrometry. This is not surprising given that we have previously, using mass spectrometry, developed a host biomarkerbased rule-out test and a rule-in test for TB, which comprises a combination of host and TB-specific biomarkers (the rule-out test is exclusively host biomarker-based when compared to a range of other diseases). The biomarker signature has been patented through the University of Cape Town. The concept of exclusively using the host response or host biomarker signature has gained traction and widespread acceptance in the TB field where blood-based signatures of risk and diagnosis, and urine-based signatures of diagnosis have been validated for this purpose, and the published data now incorporates many studies. It is envisaged that the mass spectrometry-based COVID-19 assay will be developed and immediately deployed. There is good precedent for this. Mass spectrometry-based tests are already used in the clinical service for measuring a variety of analytes including drug levels. In the future it would be attractive to develop urine-based rule-in and rule-out tests in the form of antigen capture assays or point-of-care antibody-based tests. Expected Outputs Results will be disseminated through patents, high impact journal publications, conference presentations, and press releases. However, the primary output is the development of proof-of-concept mass spectrometry-based assay for COVID-19 that can be used for disease conformation and for screening those in the community, thus improving case detection rates and control of the epidemic. The proposed study also incorporates several capacity developments and networking offsets, including the generation and strengthening of collaborations between academic and in the future commercial companies (both locally and abroad). Nascent scientists will gain new knowledge and build on their existing expertise through the partnerships with leaders in the diagnostics arena, and those with interests in platform development and commercialisation. The implications of the proposed work will include early and rapid case detection of COVID-19, potential reduction in transmission (which we will study), thereby subverting amplification of the epidemic and reducing morbidity (lung and organ damage) and mortality.