Diagnosis of COVID-19: Considerations, controversies and challenges

K Dheda1,2, S Jaumdally1, M Davids1

  • 1Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute and South African MRC/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town, South Africa.

Insights

Reverse transcription polymerase chain reaction (RT-PCR) is a key diagnostic tool for COVID-19 but has limitations. Antibody tests show promise for surveillance and understanding immunity after symptom resolution.

Area of Science:

  • Virology
  • Infectious Diseases
  • Epidemiology

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, has led to millions of cases and deaths globally.
  • Most symptomatic COVID-19 cases present with mild upper respiratory tract symptoms.
  • Accurate and timely diagnosis is crucial for managing the pandemic.

Purpose of the Study:

  • To evaluate the diagnostic utility of RT-PCR and antibody-based immunoassays for COVID-19.
  • To understand the temporal dynamics of viral RNA detection and antibody responses.
  • To explore the potential roles of different diagnostic methods in clinical management and public health.

Main Methods:

  • Reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal samples for viral RNA detection.
  • Detection of IgM and IgG antibodies following symptom onset.
  • Evaluation of antibody-based immunoassays for diagnostic and surveillance applications.

Main Results:

  • RT-PCR has an approximate 30% false-negative rate early in disease or in mild cases, often necessitating repeat testing.
  • Viral RNA detection by RT-PCR can persist post-symptom resolution.
  • IgM and IgG antibody responses become detectable several days after symptom onset, with robust responses in the second week.
  • Antibody-based immunoassays have limited utility in diagnosing early symptomatic disease but may be useful for surveillance.

Conclusions:

  • RT-PCR remains the primary diagnostic method for COVID-19, despite potential for false negatives.
  • Antibody testing is valuable for assessing past infection and immune status, aiding surveillance efforts.
  • Ongoing research is clarifying the role of antibody tests in conjunction with RT-PCR for early diagnosis and other applications, such as vaccination assessment and workforce screening.

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