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Clinical Laboratories and Pathology Groups

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Immunocompromised Patients with COVID-19 May Remain Infectious for Much Longer than Previously Thought

Clinical laboratory professionals should note that one case study describes a COVID-positive cancer patient shedding infectious particles for five months, which is much longer than expected

Just when researchers start believing they understand COVID-19 infections, something happens that reveals there is still more to learn. These additional findings are relevant for clinical laboratory managers and pathologists because the new insights often may play a role in how SARS-CoV-2 results should be interpreted for individual patients.

Researchers recently described a case where, in February, a 71-year-old woman underwent surgery related to her 10-year battle with cancer. While she was in the hospital, she was found to be positive for the SARS-CoV-2 coronavirus, though she showed no respiratory or systemic symptoms. Nevertheless, the hospital isolated her and monitored the infection.

To everyone’s surprise, the patient remained positive for five months. She underwent 15 COVID-19 tests from various diagnostics companies, as well as receiving two doses of convalescent plasma therapy, but she remained positive for the coronavirus into June.

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) wanted to know why. They conducted a study on the woman, which they later published in the journal Cell, titled, “Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer.”

In their published study, they wrote, “Although it is difficult to extrapolate from a single individual, our data suggest that long-term shedding of infectious virus may be a concern in certain immunocompromised people. Given that immunocompromised individuals could have prolonged shedding and may not have typical symptoms of COVID-19, symptom-based strategies for testing and discontinuing transmission-based precautions, as recommended by the Centers for Disease Control and Prevention (CDC), may fail to detect whether certain individuals are shedding infectious virus.”

Clinical laboratory professionals and pathologists will find it significant that patients with major health conditions may be shedding viral material for weeks longer than originally thought. This is relevant because it may be prudent to COVID test patients who present with compromised immune systems, and who are asymptomatic, and then repeat that testing at appropriate intervals.

The graphic above taken from the NIAID study
The graphic above taken from the NIAID study shows how long it took for the SARS-CoV-2 coronavirus to clear the 71-year-old immunocompromised cancer patient’s system, and at which points the convalescent plasma doses were administered. (Graphic copyright: National Institute of Allergy and Infectious Diseases.)  

Immunocompromised Patients May Handle COVID-19 Differently

The NIAID researchers believe the reason the patient continued to shed infectious virus for so long was because she was immunocompromised. They wrote, “Many current infection control guidelines assume that persistently PCR-positive individuals are shedding residual RNA and not infectious virus, with immunocompromised people thought to remain infectious for no longer than 20 days after symptom onset. Here we show that certain individuals may shed infectious, replication-competent virus for much longer than previously recognized. Although infectious virus could be detected up to day 70, sgRNA, a molecular marker for active SARS-CoV-2 replication, could be detected up until day 105.”

In the United States, some three million people have compromised or weakened immune systems. This is a significant population, Science Alert reported.

“As the virus continues to spread, more people with a range of immunosuppressing disorders will become infected, and it’s more important to understand how SARS-CoV-2 behaves in those populations,” Vincent Munster, PhD, Chief, Virus Ecology Unit at the National Institute of Allergy and Infectious Diseases and co-author of the NIAID study, told Science Alert.

The NIAID study findings match knowledge about other coronaviruses. For example, Science Alert reported that immunocompromised people with Middle East Respiratory Syndrome (MERS) have been shown to shed common seasonal coronaviruses for up to a month following infection.

Asymptomatic Patients Are a Mystery

There is still much that is unclear about asymptomatic patients. A paper published in JAMA, titled, “Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients with SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea,” questioned the viral load differences in patients who tested positive but had no symptoms compared to those who were symptomatic.

That study included 303 patients, of which 193 were symptomatic. During the course of the study, 21 of the asymptomatic patients developed symptoms, however, the viral load was similar in all of the patients, regardless of symptoms.

“Isolation of asymptomatic patients may be necessary to control the spread of SARS-CoV-2,” concluded the JAMA researchers. But how long should asymptomatic patients remain isolated?

Official Guidance Is Based on Symptoms

The CDC updated its guidelines for who should isolate and for how long in October. The guidelines cover:

  • People who have or had COVID-19 and had symptoms;
  • People who tested positive for COVID-19 but did not have symptoms;
  • People who either had severe symptoms of COVID-19 or who have a compromised immune system;
  • People who were exposed to COVID-19, and
  • People who have been reinfected.

Regarding those who are immunocompromised and had COVID-19, the CDC says they “may require testing to determine when they can be around others.”

In addition to noting that people who are immunocompromised may require additional testing, the CDC is also continuously updating its published list of people who are at risk for complications and severe illness if they contract COVID-19. However, as the NIAID study showed, even those with underlying medical conditions can be asymptomatic.

And as the NIAID researchers note, there is more to learn. “Understanding the mechanism of virus persistence and eventual clearance will be essential for providing appropriate treatment and preventing transmission of SARS-CoV-2 because persistent infection and prolonged shedding of infectious SARS-CoV-2 might occur more frequently. Because immunocompromised individuals are often cohorted in hospital settings, a more nuanced approach to testing these individuals is warranted, and the presence of persistently positive people by performing SARS-CoV-2 gRNA and sgRNA analyses on clinical samples should be investigated.”

SARS-CoV-2 Science Is Young

An additional takeaway for pathology lab professionals is the reminder that the scientific research surrounding the novel coronavirus that causes COVID-19 is very young. New insights and understanding will continue to emerge, probably for many years.

One reason why the development of vaccines for COVID-19 has been so quick is that it built on scientific knowledge of the first SARS outbreak and MERS. It’s interesting to note that both SARS and MERS are relatively new as well: SARS emerged in 2002 and MERS in 2012. Compared to a disease like HIV, which was first identified in 1959, scientists have only been working on these particular coronaviruses for a short period of time.

The NIAID study is yet another example of new knowledge and insights emerging about how SARS-CoV-2 infects individuals. Collectively, these findings make it challenging for medical laboratory professionals to stay current with everything relevant and associated with the proper interpretation of COVID-19 test results.

—Dava Stewart

Related Information:

Prolonged Infectious SARS-SoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer

Startling Case Study Finds Asymptomatic COVVID-19 Carrier Who Shed Virus for 70 Days

Shedding of Infectious Virus in Hospitalized Patients with Coronavirus Disease-2019 (COVID-19): Duration and Key Determinants

SARS-CoV-2: The Viral Shedding vs Infectivity Dilemma

Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients with SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea

When You Can Be Around Others

People with Certain Medical Conditions

NAIAD: Coronaviruses

COVID Research Updates: Immune Responses to Coronavirus Persist Beyond Six Months