ABSTRACT
Background. The COVID-19 pandemic has been marked by long-term persistence of SARS-CoV-2 in immunocompromised patients receiving B-cell-depleting therapies, with many individuals experiencing fatal COVID-19. Methods. We report an individual treated with rituximab who survived persistent COVID-19 over 9 months. SARS-CoV-2 positive RNA samples were sequenced using targeted amplicon NGS sequencing with backup sequencing on a nanopore platform. The resulting sequences were analyzed for genomic variance over time at the consensus and sub-consensus level. Results. An individual with rheumatoid arthritis (RA) treated with azathioprine and rituximab (last dose in May 2020) was diagnosed with COVID-19 in July 2020 and admitted with pneumonia. After initial incomplete recovery, the patient had persistent infection through March 2021 and received both remdesivir and convalescent plasma (January 2021). The patient received three doses of mRNA vaccine (Pfizer BioNTech) in December 2020, April 2021, and November 2021, but was seronegative for nucleocapsid IgG in both January 2021 and March 2021;positive spike IgG developed by September 2021 (512 AU/ml) and December 2021 (621 AU/ml) (Figure 1). The patient recovered with new oxygen dependence (2-3L) and manages RA off B-cell depletion;they required an extended corticosteroid taper to manage organizing pneumonia and treatment for several opportunistic infections. Viral sequencing over the course of illness indicated a persistent infection with a lineage B.1.585.3 virus that accumulated 14 mutations throughout the infection. Two mutations (S494P, S D737Y) are associated with therapy resistance and are similar to those found in other immunocompromised individuals with persistent COVID-19. Additional mutations were of unknown consequence Conclusion. SARS-CoV-2 was able to establish persistent infection and accumulated mutations associated with therapeutic resistance;repeated vaccination was associated with successful resolution following repeated vaccination after stopping rituximab. Cessation of B-cell-depleting therapy was likely the critical factor in the patient's recovery, but repeated vaccination was associated with a delayed seroconversion in this patient with reversibly immunosuppression.
ABSTRACT
Background. SARS-CoV-2 continues to spread globally, including in limited resource settings. It is therefore important to derive general case definitions that can be useful and accurate in the absence of timely test results. We aim to validate the World Health Organization (WHO) case definition, a symptom-screening tool currently used to identify SARS-CoV-2 cases in a cohort of symptomatic health care providers (HCP) who completed a symptom survey interview and received a PCR test at Boston Medical Center (BMC) between March 13, 2020 and May 5, 2020. Methods. We classified each HCP as a probable or not probable case of SARSCoV-2 based on the WHO case definition. Using PCR test as gold standard, we computed the sensitivity and specificity of the WHO case definition. We used a stepwise logistic regression model on all PCR-tested HCP to identify symptoms predictive of PCR positivity. Results. Of 328 included HCP, 109 (33.2%) were PCR positive, 213 (64.9%) negative, and 6 (1.8%) had indeterminate test result. The sensitivity and specificity of the WHO case definition were 65.1% and 74.6%, respectively. The positive predictive value was 56.8% and the negative predictive value was 80.7%. Symptoms found to be predictive of PCR positivity were fever, headache, loss of smell and/or loss of taste, and muscle ache/joint pain. Sore throat was found to be predictive of PCR negativity. The area under the curve using the final model was 0.8412. All statistically significant symptoms included in the final model, were also included in the WHO case definition. Conclusion. In our largely symptomatic HCP cohort, our model yielded similar symptoms to those identified in the WHO probable case definition. As seen in similar studies, it is unlikely that further adjustment will improve the performance of a SARSCoV-2 case definition. However, it is concerning that 35% (38/109) of PCR positive SARS-CoV-2 HCP would have been classified as not probable cases by the WHO definition, given that this definition does not even include asymptomatic cases. This is further evidence for global building of laboratory capacity and development of affordable diagnostics to improve global pandemic control.
ABSTRACT
Up until now, there is much debate about the role of asymptomatic patients and pauci-symptomatic patients in severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) transmission, and little is known about the kinetics of viral ribonucleic acid (RNA) shedding in these populations. This article aims to describe key features and the nature of asymptomatic and pauci-symptomatic SARS-CoV-2 infected patients. The cohort consisted of six participants, three pairs, which were infected with SARS-CoV-2 during February 2020 on board the Diamond Princess. Of the six confirmed (reverse transcription polymerase chain reaction [RT-PCR]) cases, four were initially diagnosed in Japan and two upon their arrival to Israel. Duration of infection was between four days and up to 26 days. Of the six patients, three were completely asymptomatic and the others were pauci-symptomatic. All five patients in whom a computerized tomography (CT) scan was performed had lung pathology. In one patient, infectivity was tested using cell culture and a cytopathic effect was demonstrated. A serology test was performed in three of the patients and all three had a positive immunoglobulin G (IgG) four to eight weeks after disease onset. This case series demonstrates that asymptomatic and pauci-symptomatic patients may play a role in infection transmission by demonstrating probable transmission among asymptomatic spouses and by demonstrating a viable virus via a cell culture. Additionally, asymptomatic and pauci-symptomatic patients can have lung pathology and developing IgG antibodies.