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Prolonged SARS-CoV-2 infection during the Omicron period was uncommon among patients who were moderately to severely immunocompromised, a prospective multicenter study found.

Among the 150 individuals included in the analysis, 25% had prolonged infection lasting 21 days or more as detected by RT-PCR, and only 8% had a positive viral culture at 21 days or beyond, Adam Lauring, MD, PhD, from the University of Michigan in Ann Arbor, and colleagues reported in .

Overall, the median time to a last positive SARS-CoV-2 test in immunocompromised patients was 9 days.

"In contrast to a lot of case reports, we were finding that very few [immunocompromised] people had prolonged infection," Lauring commented . Also, many profoundly immunocompromised people cleared their infection with antiviral drugs, monoclonal antibodies, or a combination of the two, the authors pointed out.

Notably, patients with B-cell malignancies or B-cell depleting therapies, (e.g., anti-CD19 or anti-CD20 antibodies, chimeric antigen receptor [CAR]-T therapy) were at highest risk for prolonged infection. Compared with patients taking immunosuppressive medications for autoimmune or autoinflammatory conditions, those with B-cell dysfunction (aHR 0.32, 95% CI 0.15-0.64), people who had undergone solid organ transplantation or hematopoietic stem cell transplant (HSCT; aHR 0.60, 95% CI 0.38-0.94), and those with AIDS (aHR 0.28, 95% CI 0.08-1.00) had longer duration of infection.

No other factors, including age, sex, ethnicity, vaccination status, or baseline antiviral use were associated with duration of infection.

Patients with AIDS had the longest median time to last SARS-CoV-2-positive RT-PCR (32 days), followed by those who had undergone solid organ transplant or HSCT (16 days), those with B-cell dysfunction (11 days), and people with autoimmune/autoinflammatory conditions (4 days).

Early in the COVID-19 pandemic, concerns arose about the potential for new variants to arise in immunocompromised individuals. However, in the current study, researchers found that few mutations that occurred in individual patients were shared and none became prevalent globally.

"Our analysis showed comparatively restricted SARS-CoV-2 evolution over a wide spectrum of immunocompromising conditions," the authors wrote.

Among the five patients who remained SARS-CoV-2-positive longer than 56 days, researchers identified consensus de novo spike mutations in four of them. Of these 23 mutations, 61% were in the receptor binding domain. Few of these mutations were shared among multiple patients and there was no evidence of onward transmission based on data from a global SARS-CoV-2 phylogenetic tree.

Researchers also analyzed mutational patterns according to SARS-CoV-2 treatment. Of the 16 patients who received monoclonal antibodies and also had a post-treatment sample available for analysis, 62% had de novo non-synonymous mutations in spike. Among those treated with antiviral drugs and with post-treatment samples available, de novo mutations in nsp12 occurred in seven patients treated with remdesivir (Veklury), most of which were present at very low frequency. None occurred in patients treated with nirmatrelvir-ritonavir (Paxlovid). The few patients treated with molnupiravir (Lagevrio) had high numbers of low frequency nucleotide substitutions, consistent with the drug's mutagenic mode of action.

The analysis was part of the CDC's larger Investigating Respiratory Viruses in the Acutely Ill Network study and included immunocompromised patients from five U.S. medical centers. All participants were adults (median age of 60 years) diagnosed with SARS-CoV-2 in the previous 14 days. Of the 150 patients included in the analysis, 39% had undergone solid organ transplant or HSCT, 30% had autoimmune or autoinflammatory conditions, 15% had malignancies, 12% had B-cell dysfunction, and 3% had AIDS. Almost all were vaccinated against COVID-19.

After testing positive for SARS-CoV-2, patients received antiviral treatment such as remdesivir (45%), nirmatrelvir-ritonavir (13%), or molnupiravir (3%), convalescent plasma, or early-generation monoclonal antibody therapies. Most patients eventually tested negative on RT-PCR after treatment.

Participants were tested for SARS-CoV-2 every 2 weeks until they tested negative on two successive samples. All participants in the analysis were infected with Omicron lineages, the majority of which had the BA.2 and BA.5 lineages.

One limitation of the study is that only 27% of patients had follow-up samples that tested positive by RT-PCR. Also, the study included some patients with milder immunosuppression who may not be representative of a more profoundly immunosuppressed population. People with AIDS were underrepresented while those who had received organ transplants or HSCT, CAR-T, or anti-CD20 monoclonal antibodies were overrepresented, the authors noted.

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