Biosensor Testing SARS-CoV-2 Antibody Testing Can Predict COVID-19 Severity in Patients

The 2019 coronavirus disease (COVID-19) pandemic continues to spread around the world, causing over 59.17 million confirmed infections and over 1.39 million deaths. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China in December 2019.

Understanding the size of the virus and its prevalence in a population is an essential part of containing its spread. Therefore, accurate, efficient and cost-effective testing is critical for implementing effective social distancing measures, managing local epidemics and breaking chains of transmission.

Better tests can also help predict COVID-19 severity in patients in the early stages of their encounter with the virus. Early understanding of a patient’s likely prognosis with the disease through high-sensitivity testing could enable the necessary therapeutic interventions that would mitigate its impact on those who are vulnerable to more severe or critical cases.

Research labs worked around the clock to develop better detection tests with high specificity and sensitivity. These tests aimed to detect neutralizing antibodies (NAbs), which block the spike glycoprotein (S) receptor binding domain (RBD) of SARS-CoV-2.

This NAb-RBD binding prevents the virus protein from interacting with the human angiotensin-converting enzyme 2 (ACE2) receptor, which is found in abundance in the epithelial cells lining the respiratory and intestinal tracts, which is the medium through which the virus gains entry into the host cell.

Early humoral immune response to SARS-CoV-2 can predict clinical outcome (recovery, severity, or mortality). However, due to the lack of highly sensitive serological testing methods during the first key days of the infection, this speculation has not yet been fully investigated.

In a recent prepress document published on medRxiv * server, researchers from New York, USA, found an association of mortality with an early humoral response to SARS-CoV-2 infection within the first few days of symptom onset (DAOS), using a test-on- highly sensitive and automated probe biosensor (TOP) analysis for SARS-CoV-2.

I study

Researchers report two sensitive and automated TOP biosensor tests for SARS-CoV-2 specific viral total antibodies (TAb) and surrogate neutralizing antibodies (SNAb). The competitive binding test detects SARS-CoV-2 specific viral total antibodies (TAb) and surrogate neutralizing antibodies (SNAb), using an RBD-coated quartz probe.

It also uses a Cy5-streptavidin polysaccharide conjugate to improve sensitivity and minimize any interference.

The total analysis time is 16 min. The researchers also designed the test with disposable cartridges containing pre-dispensed reagents, which means that it requires no handling of liquids or fluidics during the test.

Researchers tested the clinical utility of the biosensor by evaluating initial antibody responses in COVID-19 positive inpatient polymerase chain reaction reverse transcription (RT-PCR) patients. The study cohort involved 120 adult patients, who were admitted to New York Presbyterian / Weill Cornell Medical Center (NYP / WCMC) from March 8 to April 7, 2020.

The severity of COVID-19 has been observed with varying outcomes, leaving doctors, healthcare professionals and researchers with no idea of ​​the possible outcome during treatment or hospitalization of patients. The discrepancies in the studies observed so far depend on a variety of factors.

For the first time, researchers demonstrate in this study that SARS-CoV-2 TAb and SNAb (at initial presentation) are risk indicators for in-hospital mortality. This study uses the TOP test to match antibodies present on the first day of a hospital visit and subsequent mortality.

Probability of survival among SARS-CoV-2 infected patients with positive and negative (A) TOP-TAb and (B) TOP-SNAb at initial ED presentation in hospital. Data were analyzed using Cox proportional hazards regression adjusting for age and cancer comorbidity.

The researchers found that patients who did not have high levels of antibodies during the hospital visit were at increased risk of hospital mortality. Immediately after infection, NAbs, if present, prevent the manifestation of severe disease by limiting the number of host cells that are productively infected.

They show that higher antibody levels are associated with lower viral load.

Their findings agree with recent reports on the importance of early immunological protection in COVID-19 patients. These antibodies that appear early in the infection phase can be postulated to protect the patient from the severity of the infection and mortality; either directly playing a protective role or indirectly suppressing SARS-CoV-2 replication.

A reliable and versatile serological or antibody test detects infection early. This type of test is not yet available on the market.

Conclusion

This study reports a novel, rapid, highly sensitive and fully automated biosensor (TOP) technology that can be adapted to the clinical laboratory setting. The new tests detect the first SARS-CoV-2 antibodies on the first day of a hospital visit. The results show that SARS-CoV-2 antibody levels are inversely associated with subsequent COVID-19 mortality.

Associations between early antibody response to SARS-CoV-2, initial viral load and eventual hospital survival are consistent with strong early humoral immunity that counteracts SARS-CoV-2 replication – this could have significant implications for the management of their immediate and future care.

The researchers believe future studies will explore whether these new sensitive and specific assays could potentially monitor the effectiveness of antiviral therapies and evaluate antibody responses during vaccine trials.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as consolidated information.