The problem, the consequences, and rapid testing solutions

COVID-19 is a respiratory tract infection caused by the SARS-CoV-2 virus. Since late 2019, COVID-19 has grown into a global pandemic that has claimed more than 6.4 million lives and represents a serious public health challenge.^1-3

Despite the rapid development of vaccines, the virus remains a serious public health threat because mutations in the viral genome provide advantages in replication, immune escape, increased transmissibility and diagnostic detection failure.⁴ Rapid diagnostic testing can help to identify infected individuals and lead to their isolation to prevent onward disease spread.

 Adaptive mutations within the SARS-CoV-2 genome have led to the emergence of Variants of Concern (VOCs) that are associated with enhanced transmissibility, increased virulence and immune evasion, and have been named by the World Health Organization (WHO) as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529).⁹ The immune response elicited by the body after vaccination—termed active immunity or acquired immunity—depends on the recognition of a viral antigen by specific antibodies.^10,11 As mutations accrue, changes in the epitope interfere with antibody recognition, thereby reducing the efficacy of a vaccine.¹² Therefore, the emergence of VOCs has complicated vaccine development. There are four COVID-19 vaccines currently authorized by the FDA for emergency use: Comirnaty (Pfizer-BioNTech), Spikevax (Moderna), Janssen (Johnson & Johnson) and Novavax, Adjuvanated.¹³

Vaccine effectiveness (VE) varies between VOCs and vaccine type: full vaccination is effective against the Alpha variant and moderately effective against the Beta, Gamma and Delta variants, whereas booster vaccination is more effective against the Delta and Omicron variants.¹⁴ Additionally, mRNA vaccines such as Comirnaty (Pfizer-BioNTech) and Spikevax (Moderna) are more effective against the VOCs.14 Despite the overall effectiveness of COVID-19 vaccines, breakthrough infections have been reported.^15,16 Studies have demonstrated that there is no significant difference in SARS-CoV-2 viral load between infected individuals who are vaccinated (breakthrough cases) and the unvaccinated.^17,18 This underscores the importance of continued testing to assess infectiousness so that quarantine measures can be implemented as needed. Testing to prevent onward transmission is fundamentally different from testing to diagnose a patient with COVID-19.¹⁹ Public health screening tests should be rapid, can be performed in decentralized locations and can be scaled up to test large numbers of asymptomatic individuals.^19,20 Tests such as these (including the Panbio™ COVID-19 Ag Rapid Test Device) are simple to perform, relatively inexpensive, can be self-administered and do not require elaborate laboratory equipment.¹⁹

Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is considered the gold standard for detection of SARS-CoV-2 and can detect minute amounts of viral nucleic acid in a patient sample.²¹ Despite its high sensitivity, RT-PCR is more expensive, requires specialized laboratory equipment and trained personnel, has a higher turnaround time and is not widely available in resource-limited settings.^22-24 RT-PCR cannot, therefore, be scaled up to meet the demands of public health testing.19 The high sensitivity of RT-PCR can also produce false positive results due to the detection of residual SARS-CoV-2 RNA long after a patient is infectious.²⁵

Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities.²⁶ This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children and those not hospitalized.

Presently, there is limited literature discussing the possible pathophysiology, risk factors and treatments in long COVID.²⁶

Long COVID may be driven by long-term tissue damage (e.g., lung, brain and heart) and pathological inflammation (e.g., from viral persistence, immune dysregulation and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnea, prior psychiatric disorders, and specific biomarkers (e.g., D-dimer, C-Reactive Protein (CRP) and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID.²⁶
 

POSSIBLE RISK FACTORS (BIOMARKERS)²⁶

• Elevated blood urea nitrogen (BUN) and D-dimer levels were found to be risk factors for pulmonary dysfunction among survivors of COVID-19 at three-month, post-hospital discharge.²⁷
• Other studies have shown that COVID-19 pulmonary lesions at two-month post-admission were associated with elevated systemic inflammatory biomarkers, such as D-dimer, interleukin-6 (IL-6) and CRP.^28,29
• Systemic inflammatory biomarkers (e.g., CRP, procalcitonin and neutrophil count) also correlated with radiological abnormalities of the heart, liver and kidney in a 2- to 3-month follow-up study of discharged COVID-19 patients.³⁰
• In another study, increased D-dimer and CRP levels and decreased lymphocytes were more common in COVID-19 survivors who developed persistent symptoms than their fully recovered counterparts.³¹
• Another report also found that lymphopenia correlated with chest tightness and heart palpitations, whereas elevated troponin-1 correlated with fatigue, among sufferers of long COVID.³²

Therefore, changes in levels of D-dimer, CRP and lymphocyte appeared consistent in a few studies, and may serve as potential biomarkers of long COVID.
 

THE CONSEQUENCES

When individuals infected with the SARS-CoV-2 virus are not isolated, they can spread the virus. The solution to containing disease spread is the quick identification of infected individuals followed by quarantine. This is especially important for pre-symptomatic and asymptomatic individuals who may unknowingly spread the virus. Studies have shown that a positive or negative antigen test might be a useful proxy for the risk for being infectious,³³ and that infected individuals are more likely to transmit the virus when they test positive for the SARS-CoV-2 antigen.³⁴ Additionally, the implication of a false positive RT-PCR result can include unnecessary treatment and investigation, missing or delayed surgery, unnecessary isolation and contact tracing, and increased risk of exposure when placed with other COVID-19 patients.²⁵
 

RAPID TESTING

By testing patients and providing results quickly, antibiotics can be withheld and antivirals can be prescribed only where appropriate. Physician awareness of a rapid diagnosis of COVID-19 decreases antibiotic use.

Rapid Diagnostic Tests (RDTs) are used for the qualitative detection of either antigen or antibody biomarkers of the SARS-CoV-2 virus.³³ Rapid diagnostic testing can be performed at the point of care (POC), workplace, school or home.¹⁹ Widespread RDT deployment is valuable for population screening and surveillance for effectively limiting the spread of COVID-19.^19,20 RDTs are most effective for use in POC settings and for performing seroprevalence studies.³⁶

*Product not available in all countries. Self Test products available in select markets. Not all products approved for sale in the U.S.

The Panbio™ COVID-19 Ag Rapid Test Device, Panbio™ COVID-19 Antigen Self-Test, and Panbio™ COVID-19/Flu A&B Rapid Panel are not available for sale in the US. 

BinaxNOW™ COVID-19 Ag Card and BinaxNOW™ COVID-19 Antigen Self Test have not been FDA cleared or approved, but have been authorized for emergency use by FDA under an EUA. They have been authorized only for the detection of proteins from SARS-CoV-2, not for any other viruses or pathogens. BinaxNOW™ COVID-19 Antigen Self Test should be performed twice in 3 days, at least 24 hours apart (and no more than 48 hours) apart.

ID NOW™ COVID-19 and ID NOW™ COVID-19 2.0 have not been FDA cleared or approved, but have been authorized for emergency use by FDA under an EUA for use by authorized laboratories. They have been authorized only for the detection of nucleic acid from SARS-CoV-2, not for any other viruses or pathogens. 

The emergency use of the BinaxNOW™ COVID-19 Ag Card, BinaxNOW™ COVID-19 Antigen Self Test, ID NOW™ COVID-19, and ID NOW™ COVID-19 2.0 products are only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization is revoked sooner.