Background: Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown. Objective: Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response. Methods: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting > _21 days) or relapsing (> _2 episodes) of COVID-19. Results: We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of < _20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2. Conclusions: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise. (J Allergy Clin Immunol 2021;nnn:nnn-nnn.)

The group difference in HC growth rate may differentiate brain development in individuals with FXS-only versus those with FXS + ASD.

Background Patients infected with novel COVID-19 virus have a spectrum of illnesses ranging from asymptomatic to death. Data has shown that age, gender and obesity are strongly correlated with poor outcomes in COVID-19 positive patients. Bariatric surgery is the only treatment that provides significant, sustained weight loss in the severely obese. Objectives Examine if prior bariatric surgery correlates with increased risk of hospitalization and outcome severity after COVID-19 infection. Setting University Hospital Methods A cross-sectional retrospective analysis of a COVID-19 database from a single, NYC-based, academic institution was conducted. A cohort of COVID-19 positive patients with a history of bariatric surgery (n=124) were matched in a 1:4 ratio to a control cohort of COVID-19 positive patients who were eligible for bariatric surgery (BMI > 40 kg/m 2 or BMI > 35 kg/m 2 with a comorbidity at the time of COVID-19 diagnosis) (n=496). A comparison of outcomes, including mechanical ventilation requirements and deceased at discharge, was done between cohorts using Chi-square test or Fisher’s exact test. Additionally, overall length of stay and duration of time in ICU were compared using Wilcoxon Rank Sum test. Conditional logistic regression analyses were done to determine both unadjusted (UOR) and adjusted odds ratios (AOR). Results A total of 620 COVID-19 positive patients were included in this analysis. The categorization of bariatric surgeries included 36% Roux-en-Y Gastric Bypass (RYGB, n=45), 35% laparoscopic adjustable gastric banding (LAGB, n=44), and 28% laparoscopic sleeve gastrectomy (LSG, n=35). The body mass index (BMI) for the bariatric group was 36.1 kg/m 2 (SD=8.3), which was significantly lower than the control group, 41.4 kg/m 2 (SD=6.5) (p<0.0001). There was also less burden of diabetes in the bariatric group (32%) compared to the control group (48%) (p=0.0019). Patients with a history of bariatric surgery were less likely to be admitted through the emergency room (UOR=0.39, p=0.0001), less likely to require a ventilator during the admission (UOR=0.42, p=0.028), had a shorter length of stay in both the ICU (p=0.033) and overall (UOR=0.44, p=0.0002), and were less likely to be deceased at discharge compared to the control group (OR=0.42, p=0.028). Conclusion A history of bariatric surgery significantly decreases the risk of emergency room admission, mechanical ventilation, prolonged ICU stay, and death in patients with COVID-19. Even when adjusted for BMI and the comorbidities associated with obesity, patients with a history of bariatric surgery still have a significant decrease in the risk of emergency room admission.

There is widespread interest in the capacity for SARS-CoV-2 evolution in the face of selective pressures from host immunity, either naturally acquired post-exposure or from vaccine acquired immunity. Allied to this is the potential for long perm persistent infections within immune compromised individuals to allow a broader range of viral evolution in the face of sub-optimal immune driven selective pressure. Here we report on an immunocompromised individual who is hypogammaglobulinaemic and was persistently infected with SARS-CoV-2 for over 290 days, the longest persistent infection recorded in the literature to date. During this time, nine samples of viral nucleic acid were obtained and analysed by next-generation sequencing. Initially only a single mutation (L179I) was detected in the spike protein relative to the prototypic SARS-CoV-2 Wuhan-Hu-1 isolate, with no further changes identified at day 58. However, by day 155 the spike protein had acquired a further four amino acid changes, namely S255F, S477N, H655Y and D1620A and a two amino acid deletion (ΔH69/ΔV70). Infectious virus was cultured from a nasopharyngeal sample taken on day 155 and next-generation sequencing confirmed that the mutations in the virus mirrored those identified by sequencing of the corresponding swab sample. The isolated virus was susceptible to remdesivir in vitro, however a 17-day course of remdesivir started on day 213 had no effect on the viral RT-PCR cycle threshold (Ct) value. On day 265 the patient was treated with the combination of casirivimab and imdevimab. The patient experienced progressive resolution of all symptoms over the next 8 weeks and by day 311 the virus was no longer detectable by RT-PCR. The ΔH69/ΔV70 deletion in the N-terminus of the spike protein which arose in our patient is also present in the B.1.1.7 variant of concern and has been associated with viral escape mutagenesis after treatment of another immunocompromised patient with convalescent plasma. Our data confirms the significance of this deletion in immunocompromised patients but illustrates it can arise independently of passive antibody transfer, suggesting the deletion may be an enabling mutation that compensates for distant changes in the spike protein that arise under selective pressure.

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