Successful treatment of SARS-CoV-2 in an immunocompromised patient with persistent infection for 245 days: A case report.

Background: Immunocompromised patients receiving B-cell-depleting therapies are at increased risk of persistent SARS-CoV-2 infection, with many experiencing fatal outcomes. We report a successful outcome in a patient with rheumatoid arthritis (RA) on rituximab diagnosed with COVID-19 in July 2020 with persistent infection for over 245 days. Results: The patient received numerous treatment courses for persistent COVID-19 infection, including remdesivir, baricitinib, immunoglobulin and high doses of corticosteroids followed by a prolonged taper due to persistent respiratory symptoms and cryptogenic organizing pneumonia. Her clinical course was complicated by Pseudomonas aeruginosa sinusitis with secondary bacteremia, and cytomegalovirus (CMV) viremia and pneumonitis. SARS-CoV-2 positive RNA samples were extracted from two nasopharyngeal swabs and sequenced using targeted amplicon Next-Generation Sequencing which were analyzed for virus evolution over time. Viral sequencing indicated lineage B.1.585.3 SARS-CoV-2 accumulated Spike protein mutations associated with immune evasion and resistance to therapeutics. Upon slowly decreasing the patient's steroids, she had resolution of her symptoms and had a negative nasopharyngeal SARS-CoV-2 PCR and serum CMV PCR in March 2021. Conclusion: A patient with RA on B-cell depleting therapy developed persistent SARS-CoV-2 infection allowing for virus evolution and had numerous complications, including viral and bacterial co-infections with opportunistic pathogens. Despite intra-host evolution with a more immune evasive SARS-CoV-2 lineage, it was cleared after 245 days with reconstitution of the patient's immune system.

Viral Dynamics of Omicron and Delta Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants With Implications for Timing of Release from Isolation: A Longitudinal Cohort Study.

BACKGROUND: In January 2022, US guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask-wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown. METHODS: We conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for reverse-transcription polymerase chain reaction (RT-PCR) testing and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4-6 compared with culture. RESULTS: Among 92 SARS-CoV-2 RT-PCR-positive participants, all completed the initial vaccine series; 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset, with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For 14 substudy participants, sensitivity and specificity of day 4-6 RDT were 100% and 86%, respectively. CONCLUSIONS: The majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though guidance to mask for days 6-10 is supported by our finding that 17% of participants remained culture-positive after isolation.

Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.

Background: In January 2022, United States guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown. Methods: We conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for RT-PCR and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by SARS-CoV-2 variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4-6 compared to culture. Results: Among 92 SARS-CoV-2 RT-PCR positive participants, all completed the initial vaccine series, 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For the 14 sub-study participants, sensitivity and specificity of RDT were 100% and 86% respectively. Conclusions: The majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though masking for a full 10 days is necessary to prevent transmission from the 17% of individuals who remain culture positive after isolation. Main Point: Beyond day 5, 17% of our Delta and Omicron-infected cohort were culture positive. We saw no significant impact of booster vaccination on within-host Omicron viral dynamics. Additionally, we found that rapid antigen testing may provide reassurance of lack of infectiousness.