Prolonged SARS-CoV-2 Shedding Possible With Immunocompromise

By Will Boggs MD

November 02, 2020

NEW YORK (Reuters Health) - Shedding of infectious SARS-CoV-2 can continue for months in immunocompromised patients, according to a case report.

"We weren't surprised that someone with immune problems might have a longer disease course and be contagious for more time than your typical patient," Dr. Adam S. Lauring of the University of Michigan, in Ann Arbor, told Reuters Health by email. "But this went on for over 100 days with ups and downs along the way."

While individuals with COVID-19 can test positive for SARS-CoV-2 RNA up to six weeks after symptom onset, infectious virus is generally not detected beyond seven days after symptom onset, research suggests.

However, patients with primary or secondary immunodeficiencies have been underrepresented in most studies and may differ in their degree of shedding, kinetics of immune clearance and disease severity, Dr. Lauring and colleagues note in the Journal of Infectious Diseases.

The team describes the virological and clinical course of a 60-year-old man with a history of refractory mantle-cell lymphoma and COVID-19. Upon initial presentation, they write, the man was afebrile but neutropenic and a nasopharyngeal swab tested positive for SARS-CoV-2 RNA by RT-PCR.

On day 7 of his illness, the patient was admitted for monitoring in the setting of chemotherapy-associated neutropenia and severe thrombocytopenia. He was discharged home with improved symptoms six days later (day 13).

He returned to the emergency department on day 22 after his symptoms worsened. A nasopharyngeal swab was again positive for SARS-CoV-2 by RT-PCR. On day 29, repeat nasopharyngeal and sputum samples were both positive for SARS-CoV-2 by RT-PCR.

Serologic testing on day 30 was negative for antibodies to SARS-CoV-2, but his sputum remained positive for SARS-CoV-2 on days 33 and 38. He was again discharged home in improved condition on day 39.

Repeat serologic testing on day 66 detected IgG antibodies to SARS-CoV-2, but nasopharyngeal testing for SARS-CoV-2 RNA remained positive on days 47, 57, 66, 81, and 106.

On day 156 of illness, when the patient was readmitted due to progression of his lymphoma, SARS-CoV-2 testing remained positive.

Respiratory tract specimens cultured on Vero E6 cells demonstrated the presence of infectious virus from days 7 through 119 of the patient's illness. Sequencing of the virus demonstrated progressive evolution with additional substitutions over time, but phylogenetic analysis essentially ruled out reinfection.

"Clinically, (this case) raised real challenges related to how to manage both his COVID-19 and his cancer," Dr. Lauring said. "He got better each time he was treated with remdesivir and convalescent plasma, but these treatments were not enough to clear the virus. It kept coming back."

"From a public-health perspective, we assumed this patient was potentially contagious the whole time," he said. "This has made us think hard about how to manage immunocompromised patients in our health system. The CDC guidelines suggest that you should assume that immunocompromised individuals will be contagious for up to 20 days. However, this patient may have been contagious for much, much longer. He didn't 'fit' the guidelines."

"We have a lot to learn about which immunocompromised patients we need to worry about," Dr. Lauring said. "Cases like this one are probably pretty rare, but I am sure that there are others out there. These patients have a lot to teach us about how the body responds to SARS-CoV-2."

"We also need better ways of determining who is still contagious," he said. "We had clues that this patient might be having prolonged viral replication, but routinely culturing the virus is not an option for most clinical labs. So, there's a need for some other test that can tell you whether the patient is infectious or not."

SOURCE: Journal of Infectious Diseases, online October 22, 2020.