Is follow-up Polymerase Chain Reaction (PCR) testing indicated for patients clinically recovering from Coronavirus Disease 2019 (COVID-19)?

From the Guidelines

Follow-up PCR testing is generally not indicated for patients clinically recovering from COVID-19. This recommendation is based on the fact that many recovered patients may continue to shed viral RNA fragments that can be detected by PCR tests for weeks or even months after infection, despite no longer being infectious 1. The persistence of detectable viral RNA does not necessarily indicate ongoing infectivity or illness requiring continued isolation.

Clinical Considerations

When deciding whether to perform follow-up PCR testing, several factors should be considered:

• The patient's clinical improvement, including resolution of fever for at least 24 hours without antipyretic medications
• The time since symptom onset, typically 5-10 days depending on symptom severity and resolution
• The patient's immune status, with severely immunocompromised patients potentially requiring a more cautious approach
• The need for admission to settings with vulnerable populations, where additional testing might be considered

Testing Limitations

It is essential to recognize the limitations of PCR testing in this context. Reliance on nasopharyngeal swabs alone to guide clinical decisions is not recommended due to the potential for false-negative results and the shift of the virus from the upper to the lower airway during disease progression 1. Furthermore, serological testing also has significant limitations, including false-negatives and false-positives, and there is no evidence to date demonstrating that SARS-CoV-2 seropositivity protects against re-infection or is durable 1.

Healthcare Resource Utilization

Healthcare resources are better utilized by focusing on testing symptomatic individuals and those with new exposures rather than confirming recovery in those already improving clinically. A symptoms-based approach is recommended due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing 1.

From the Research

Follow-up PCR Testing for Clinically Recovering COVID-19 Patients

• The necessity of follow-up Polymerase Chain Reaction (PCR) testing for patients clinically recovering from Coronavirus Disease 2019 (COVID-19) is a topic of interest in the medical community 2, 3, 4.
• A study published in 2021 found that patients who tested positive for COVID-19 after recovery may not be infectious, as none of the 4079 individuals who had close contact with these patients tested positive for SARS-CoV-2 4.
• Another study from 2021 suggested that the presence of mild symptoms in patients who tested positive over 100 days after becoming asymptomatic could be diagnosed as reinfection, indicating the potential need for follow-up PCR testing 2.
• However, a study published in the Journal of Clinical Medicine found that patients clinically recovered for at least three days showed viral clearance at viral culture and were presumably not contagious, which may reduce the need for follow-up PCR testing 3.

Diagnostic Accuracy and Testing Algorithms

• The diagnostic accuracy of serological tests for SARS-CoV-2 antibodies varies remarkably in clinical practice, and the sensitivity to identify patients with previous COVID-19 deviates substantially from the manufacturer's specifications 5.
• A consensus statement from a panel of Latin American experts proposed testing algorithms for the use of RT-PCR and serological high-affinity antibodies tests in different settings, including asymptomatic subjects exposed to a SARS-CoV-2 infected person and symptomatic subjects 6.
• The use of serological high-affinity SARS-CoV-2 antibodies tests can contribute greatly to public health strategies, such as population screening and supporting vaccination planning, but the ideal timing for these tests is ideally 21 days after potential infectious contact 6.

Implications for Follow-up PCR Testing

• The available evidence suggests that follow-up PCR testing may not be necessary for all clinically recovering COVID-19 patients, as the risk of reinfection or transmission may be low 3, 4.
• However, follow-up PCR testing may be indicated in certain cases, such as patients who develop mild symptoms after recovery or those who are at high risk of reinfection 2.
• Further research is needed to determine the optimal testing strategies and algorithms for follow-up PCR testing in clinically recovering COVID-19 patients 5, 6.