ABSTRACT
Background. Most individuals diagnosed with mild to moderate COVID-19 are no longer infectious after day 10 of symptom onset and those with severe or critical illness from COVID are typically not infection after day 20 day of symptom onset. Recovered persons can continue to test positive for SARS-CoV-2 by PCR via detection of non-viable RNA in nasopharyngeal specimens for up to three months (or longer) after illness onset. It is also know known that severely immunocompromised patients may produce replication-competent virus greater than 20 days from symptom onset and may require, per CDC recommendations, "additional testing and consultation with infectious diseases specialists and infection control experts". We aim to discuss four case studies of severely immunocompromised patients who exhibited signs of persistent COVID-19 infection of COVID and how we managed transmission-based precautions in our hospital through sequencing and evaluation of cycle thresholds (CT) values and subgenomic RNA detection. Methods. Residual nasopharyngeal (NP) samples were collected on patients exhibiting persistent COVID like symptoms. These samples underwent N gene and N gene subgenomic RNA (sgRNA) real-time reverse transcription polymerase chain reaction (rRT-PCR) testing. Results. Analysis of longitudinal SARS-CoV-2 sequence data demonstrated within-patient virus evolution, including mutations in the receptor binding domain and deletions in the N-terminal domain of the spike protein, which have been implicated in antibody escape. See Figures 1 and 2. Figure 1. Timelines of Identified Patients 1 and 2 Patient 1: 46-year-old woman with recently diagnosed stage IV diffuse large B-cell lymphoma for which she was treated with 2 cycles of R-CHOP. Patient 2: 38-year-old woman with history of myelodysplastic syndrome, peripheral blood stem cell transplant with chronic graft versus host disease of the GI tract, skin, and eyes as well as CMV enteritis, and she was maintained on rituximab, mycophenolate mofetil, prednisone, and monthly IVIG without recent changes to her immunosuppression. Figure 2. Timeline of Identified Patients 3 and 4 Patient 3: 44 year-old man with prior history of thymoma s/p thymectomy Patient 4: 46 year-old man who was initially diagnosed with marginal zone lymphoma approximately 2.5 years ago. He was initially treated with bendamustine and rituximab and achieved remission. He was then continued on maintenance rituximab without significant complications for a planned two years. Conclusion. Differentiating between prolonged viral shedding of non-infectious RNA and persistent replicating viable virus can be difficult to determine without full evaluation of a patient's clinical picture and timeline. Consultation between laboratory, infectious diseases, and infection prevention experts to provide appropriate level of guidance for precautions and treatment may be warranted. Testing by PCR and analysis of CT values may provide key findings of viral replication in immunocompromised hosts, indicating the need for evaluation of additional treatment and maintaining isolation status in healthcare settings.
ABSTRACT
Purpose: US Solid organ transplantation rates significantly decreased during the initial wave of the COVID-19 pandemic. The concern for potential donor derived COVID-19 was one of many contributing factors. We describe the early experience of the Organ Procurement and Transplantation Network (OPTN) Disease Transmission Advisory Committee (DTAC) Coronavirus disease 2019 (COVID-19) investigations. Methods: COVID-19 cases reported to DTAC between January 2020 and October 2020 as potential donor-derived transmission events (PPDTE) were included. All of the events were investigated by the Centers for Disease Control and Prevention and adjudicated by the DTAC based on consensus definitions. Results: Eighteen PDTE COVID-19 events were reported during the study period. 12 PDTE reports have completed DTAC adjudication (Table 1). These included 12 donors with 44 recipients. Ten investigations were initiated by the transplant center due to recipient testing (36 total recipients). The median time to presentation in these index cases was 11 days (IQR 7-16). Nine donors in these events (35 recipients) had a prospective or retrospective pre-recovery negative SARS-CoV-2 PCR result. In all of these events, the index recipient had either a possible or confirmed community or hospital exposure. In one recipient index case (5 total recipients), the positive SARS-CoV-2 PCR result post-transplant was ultimately deemed a false positive and considered not a case by the committee. Two investigations were initiated by an OPO (8 recipients). In both events, the OPO performed SARS-CoV-2 PCR was negative, but a post-procurement nasopharyngeal SARS-CoV-2 PCR performed by the tissue collector was reported as positive and retrospectively deemed false positives. None of these recipients developed COVID-19;the events were adjudicated as not cases. Conclusions: The initial DTAC experience reflecting the early pandemic era emphasizes the need to implement hospital prevention measures to avoid nosocomial transmission, provide patient education to avoid community exposure and to recognize the possibility of post-procurement SARS-CoV-2 false positive testing. Vigilance for the possibility of a SARS-CoV-2 donor derived event remains important as the pandemic continues. (Table Presented) .