Why some Covid-19 patients have tested positive twice
A question I get frequently asked by friends and family members these days is: “Can people get Covid-19 again after they have recovered?”
This is a question that stems from the fear raised by multiple media outlets recently reporting identification of SARS-CoV-2 (the novel coronavirus causing Covid-19) in 141 South Korean patients who had recovered from Covid-19 and tested positive again after being tested negative for the virus.
Reinfection is a common phenomenon with respiratory viruses such as influenza, respiratory syncytial virus (RSV), rhinovirus, and other seasonal coronaviruses.
While reinfection with some respiratory viruses (such as influenza virus) causes severe disease, others (RSV) can cause only mild disease.
To understand reinfection, we first need to understand what happens to our body when we get infected with a virus.
Immediately after infection, our body produces a nonspecific immune response which helps us fight the infection and may even prevent us from developing symptoms of the disease.
This non-specific response is followed by pathogen-specific responses produced by antibodies, also known as immunoglobulins. Persistence of the virus-specific antibody protects us from future re-infection with the same virus.
The antibody response to the other two novel coronaviruses including SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) can last from between six months to two years, which means that, beyond that period, one can potentially get re-infected with these viruses.
However, because SARS-CoV has been eradicated, we do not know about reinfection and there is limited information about reinfection with MERS.
SARS-CoV-2 is yet another novel virus which means we have no prior knowledge of this specific virus. Since the first reported case of Covid-19 in late December 2019, globally scientists are trying to unveil the virus at an unprecedented speed.
Many questions still remain unanswered, one such being antibody response in patients who recover from Covid-19 and the protection against reinfection.
The test that is routinely used to identify and confirm Covid-19 patients is a molecular test based on the PCR technique (polymerase chain reaction).
Respiratory samples such as the throat or nasal swabs, saliva, sputum, or bronchoalveolar lavage are used to conduct PCR tests.
In patients with suspected symptoms, a positive PCR test for SARS-CoV-2 is often confirmed for Covid-19.
However, the PCR technique only identifies parts of the virus (RNA particle) and does not provide any information about whether the virus is infective or dead or if the person had a previous infection with the virus.
To understand whether the virus is alive and infective, we need to grow or culture the virus in living cells which is a sophisticated and complex method. PCR for SARS-CoV-2 viral RNA detection is a highly sensitive technique.
Nevertheless, the performance of PCR depends on factors such as sample types (upper respiratory vs lower respiratory samples, throat swabs vs nasal swabs), different stages of infection in patients (symptomatic vs symptomatic infection, mild disease vs severe disease), the skill of sample collection, and the quality and consistency of the PCR assays being used.
A PCR test result is also dependent on how long the virus particles are shed in respiratory samples. Once a person recovers fully from Covid-19, they can still shed “non-infective” virus particles (RNA fragments) which can be identified through the PCR technique beyond 30 days of disease onset.
For now, what we know of the South Korean patients is that patients who were tested positive again for Covid-19 after a full recovery by PCR technique were most likely not infective and were tested positive for any or all of the above PCR performance-related issues.
On the other hand, serological tests, that use blood samples from patients instead of respiratory samples, detect levels of pathogen (in this case SARS-CoV-2) specific antibody, which is the marker of recent or past infection.
Serological tests are rapid and less labour intensive. Multiple serological tests to identify antibody response against SARS-CoV-2 have been developed but their validity and reliability are still being tested.
Interpretation of serological tests depends on understanding the patient’s antibody response against the specific pathogen. Because SARS-CoV-2 is a new virus, the antibody response in Covid-19 patients remains unclear.
The data available till now suggest that the antibody against SARS-CoV-2 starts to peak within two weeks of the onset of disease.
However, how long the antibody persists is not known, hence remains the question: Will I get Covid-19 again?
To understand antibody response to SARS-CoV-2 we need population-based serological data (often referred to as serosurvey) from multiple sites.
Ideally, such surveys should not only test blood samples from people who had and who did not (or who had an asymptomatic infection) have Covid-19 but also from people who had a mild, moderate, and severe case of Covid-19 to better understand different stages of infection and antibody response.
Additionally, we need long-term follow-up serological data from patients who recovered from Covid-19, potentially collected over one to two years to determine how long the SARS-CoV-2 specific antibody persists in our body and how will persistence of the antibody provide us immunity against future re-infections.
Dr Nusrat Homaira, Respiratory Epidemiologist and Senior Lecturer University of New South Wales, Sydney and Sydney Children’s Hospital.