Epidemiology, Timing, and Secondary Prophylaxis of Recurrent Nocardiosis.

Background: Nocardia tends to cause infection in immunocompromised patients or those with chronic pulmonary disease. Nocardia is known to recur, prompting the practice of secondary prophylaxis in patients perceived at high risk. However, few data exist regarding the epidemiology of recurrent nocardiosis or the effectiveness of secondary prophylaxis. Methods: We performed a multicenter, retrospective cohort study of adults diagnosed with nocardiosis from November 2011 to April 2022, including patients who completed primary treatment and had at least 30 days of posttreatment follow-up. Propensity score matching was used to analyze the effect of secondary prophylaxis on Nocardia recurrence. Results: Fifteen of 303 (5.0%) patients developed recurrent nocardiosis after primary treatment. Most recurrences were diagnosed either within 60 days (N = 6/15, 40.0%) or between 2 to 3 years (N = 4/15, 26.7%). Patients with primary disseminated infection tended to recur within 1 year, whereas later recurrences were often nondisseminated pulmonary infection. Seventy-eight (25.7%) patients were prescribed secondary prophylaxis, mostly trimethoprim-sulfamethoxazole (N = 67/78). After propensity-matching, secondary prophylaxis was not associated with reduced risk of recurrence (hazard ratio, 0.96; 95% confidence interval, .24-3.83), including in multiple subgroups. Eight (53.3%) patients with recurrent nocardiosis required hospitalization and no patients died from recurrent infection. Conclusions: Recurrent nocardiosis tends to occur either within months because of the same Nocardia species or after several years with a new species. Although we did not find evidence for the effectiveness of secondary prophylaxis, the confidence intervals were wide. However, outcomes of recurrent nocardiosis are generally favorable and may not justify long-term antibiotic prophylaxis for this indication alone.

Risk of cytomegalovirus infection and subsequent allograft failure after pancreas transplantation.

Cytomegalovirus (CMV) is a common cause of infection after transplantation, but few studies have evaluated its epidemiology, risk factors, and outcomes among pancreas transplant recipients. We performed a retrospective cohort study of adults who underwent pancreas transplantation from January 1, 2010, through December 31, 2020, at 3 sites in Arizona, Florida, and Minnesota. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or infection requiring antiviral therapy. The secondary outcome was pancreas allograft failure. Among 471 pancreas transplant recipients, 117 (24.8%) developed csCMVi after a median of 226 (interquartile range 154-289) days. CMV donor (D)+/R- patients had a significantly higher incidence of csCMVi (hazard ratio [HR] 4.01, 95% confidence interval [CI] 2.10-7.64; P < .001). In adjusted analysis, a lower absolute lymphocyte count (ALC) was associated with a greater risk of csCMVi among seropositive recipients (HR 1.39 per 50% decrease, 95% CI 1.13-1.73; P = .002) but not among D+/R- patients (HR 1.04 per 50% decrease, 95% CI 0.89-1.23; P = .595). csCMVi, lower ALC, and acute rejection (P < .001) were independently associated with pancreas allograft failure. In conclusion, CMV D+/R- was associated with csCMVi in pancreas recipients, although ALC was associated with csCMVi only among seropositive patients. The development of csCMVi in pancreas recipients was associated with poor pancreas allograft outcomes.

BK polyomavirus DNAemia in pancreas transplant recipients compared to pancreas-kidney recipients.

BACKGROUND: BK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non-kidney transplant recipients, data are limited regarding its epidemiology and outcomes in pancreas transplant recipients. METHODS: We conducted a retrospective cohort study of adults who underwent pancreas transplantation from 2010-2020. The primary outcome was BKV DNAemia. Secondary outcomes were estimated glomerular filtration rate (eGFR) reduction by 30%, eGFR < 30 mL/min/1.73 m2 , endstage kidney disease, and pancreas allograft failure. Cox regression with time-dependent variables was utilized. RESULTS: Four hundred and sixty-six patients were analyzed, including 74, 46, and 346 with pancreas transplant alone (PTA), pancreas-after-kidney, or simultaneous pancreas-kidney transplants, respectively. PTA recipients experienced a lower incidence of BKV DNAemia (8.8% vs. 32.9%; p < .001) and shorter duration of DNAemia (median 28.0 vs. 84.5 days). No PTA recipients with BKV DNAemia underwent kidney biopsy or developed endstage kidney disease. Lymphopenia, non-PTA transplantation, and older age were associated with BKV DNAemia, which itself was associated with pancreas allograft failure (adjusted hazard ratio 2.14, 95% confidence interval 1.27-3.60; p = .004). Among PTA recipients, BKV DNAemia was not associated with eGFR reduction or eGFR < 30 mL/min/1.73 m2 . CONCLUSIONS: BKV DNAemia was common among PTA recipients, though lower than a comparable group of pancreas-kidney recipients. However, BKV DNAemia was not associated with adverse native kidney outcomes and no PTA recipients developed endstage kidney disease. Conversely, BKV DNAemia was associated with pancreas allograft failure. Further studies are needed to estimate the rate of BKV nephropathy in this population, and further evaluate long-term kidney outcomes.

Mortality After Nocardiosis: Risk Factors and Evaluation of Disseminated Infection.

Background: Nocardia primarily infects patients who are immunocompromised or those with chronic lung disease. Although disseminated infection is widely recognized as an important prognostic factor, studies have been mixed on its impact on outcomes of nocardiosis. Methods: We performed a retrospective cohort study of adults with culture-confirmed nocardiosis. Advanced infection was defined as disseminated infection, cavitary pulmonary infection, or pleural infection. The primary outcome was 1-year mortality, as analyzed by multivariable Cox regression. Results: Of 511 patients with culture growth of Nocardia, 374 (73.2%) who had clinical infection were included. The most common infection sites were pulmonary (82.6%), skin (17.9%), and central nervous system (14.2%). In total, 117 (31.3%) patients had advanced infection, including 74 (19.8%) with disseminated infection, 50 (13.4%) with cavitary infection, and 18 (4.8%) with pleural infection. Fifty-nine (15.8%) patients died within 1 year. In multivariable models, disseminated infection was not associated with mortality (hazard ratio, 1.16; 95% CI, .62-2.16; P = .650) while advanced infection was (hazard ratio, 2.48; 95% CI, 1.37-4.49; P = .003). N. farcinica, higher Charlson Comorbidity Index, and culture-confirmed pleural infection were also associated with mortality. Immunocompromised status and combination therapy were not associated with mortality. Conclusions: Advanced infection, rather than dissemination alone, predicted worse 1-year mortality after nocardiosis. N. farcinica was associated with mortality, even after adjusting for extent of infection. While patients who were immunocompromised had high rates of disseminated and advanced infection, immunocompromised status did not predict mortality after adjustment. Future studies should account for high-risk characteristics and specific infection sites rather than dissemination alone.

Impact of Perioperative Prophylaxis With Enterococcus Activity on Risk of Surgical-Site Infection After Pancreas Transplantation.

Surgical-site infection (SSI) is the most common early infectious complication after pancreas transplantation (PT). Although SSI has been shown to worsen outcomes, little data exist to guide optimal choices in perioperative prophylaxis. Methods: We performed a retrospective cohort study of PT recipients from 2010-2020 to examine the effect of perioperative antibiotic prophylaxis with Enterococcus coverage. Enterococcus coverage included antibiotics that would be active for penicillin-susceptible Enterococcus isolates. The primary outcome was SSI within 30 d of transplantation, and secondary outcomes were Clostridioides difficile infection (CDI) and a composite of pancreas allograft failure or death. Outcomes were analyzed by multivariable Cox regression. Results: Of 477 PT recipients, 217 (45.5%) received perioperative prophylaxis with Enterococcus coverage. Eighty-seven recipients (18.2%) developed an SSI after a median of 15 d from transplantation. In multivariable Cox regression analysis, perioperative Enterococcus prophylaxis was associated with reduced risk of SSI (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.35-0.96; P = 0.034). Anastomotic leak was also significantly associated with elevated risk of SSI (HR 13.95; 95% CI, 8.72-22.32; P < 0.001). Overall, 90-d CDI was 7.4%, with no difference between prophylaxis groups (P = 0.680). SSI was associated with pancreas allograft failure or death, even after adjusting for clinical factors (HR 1.94; 95% CI, 1.16-3.23; P = 0.011). Conclusions: Perioperative prophylaxis with Enterococcus coverage was associated with reduced risk of 30-d SSI but did not seem to influence risk of 90-d CDI after PT. This difference may be because of the use of beta-lactam/beta-lactamase inhibitor combinations, which provide better activity against enteric organisms such as Enterococcus and anaerobes compared with cephalosporin. Risk of SSI was also related to anastomotic leak from surgery, and SSI itself was associated with subsequent risk of a poor outcome. Measures to mitigate or prevent early complications are warranted.

Outcomes of transplant recipients with pretransplant Nocardia colonization or infection.

BACKGROUND: Specific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied. METHODS: We performed a retrospective study from three centers in Arizona, Florida, and Minnesota of patients with Nocardia infection or colonization who subsequently underwent solid organ or hematopoietic stem cell transplantation from November 2011 through April 2022. Outcomes included posttransplant Nocardia infection and mortality. RESULTS: Nine patients with pretransplant Nocardia were included. Two patients were deemed colonized with Nocardia, and the remaining seven had nocardiosis. These patients underwent bilateral lung (N = 5), heart (N = 1), heart-kidney (N = 1), liver-kidney (N = 1), and allogeneic stem cell transplantation (N = 1) at a median of 283 (interquartile range [IQR] 152-283) days after Nocardia isolation. Two (22.2%) patients had disseminated infection, and two were receiving active Nocardia treatment at the time of transplantation. One Nocardia isolate was resistant to trimethoprim-sulfamethoxazole (TMP-SMX) and all patients received TMP-SMX prophylaxis posttransplant, often for extended durations. No patients developed posttransplant nocardiosis during a median follow-up of 1.96 (IQR 0.90-6.33) years. Two patients died during follow-up, both without evidence of nocardiosis. CONCLUSIONS: This study did not identify any episodes of posttransplant nocardiosis among nine patients with pretransplant Nocardia isolation. As patients with the most severe infections may have been denied transplantation, further studies with larger sample sizes are needed to better analyze any impact of pretransplant Nocardia on posttransplant outcomes. However, among patients who receive posttransplant TMP-SMX prophylaxis, these data suggest pretransplant Nocardia isolation may not impart a heightened risk of posttransplant nocardiosis.

Risk factors and prophylaxis for nocardiosis in solid organ transplant recipients: A nested case-control study.

BACKGROUND: Nocardia is an opportunistic pathogen that primarily affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Up to 2.65% of SOT recipients develop nocardiosis; however, few studies have examined risk factors and prophylaxis for nocardiosis. METHODS: We performed a multicenter, matched nested case-control study of adult SOT recipients with culture-confirmed nocardiosis from 2000 through 2020. Controls were matched up to 2:1 by sex, first transplanted organ, year of transplant, transplant center, and adequate post-transplant follow-up. Multivariable conditional logistic regression was performed to analyze associations with nocardiosis. Cox proportional hazards regression compared 12-month mortality between infection and uninfected patients. RESULTS: One hundred and twenty-three SOT recipients were matched to 245 uninfected controls. Elevated calcineurin inhibitor level, acute rejection, cytomegalovirus infection, lymphopenia, higher prednisone dose, and older age were significantly associated with nocardiosis while trimethoprim-sulfamethoxazole prophylaxis was protective (odds ratio [OR] .34; 95% confidence interval [CI] .13-.84). The effect of prophylaxis was similar, though not always statistically significant, in sensitivity analyses that only included prophylaxis dosed more than twice-per-week (OR .30; 95% CI .11-.80) or restricted to years 2015-2020 (OR .33, 95% CI .09-1.21). Nocardiosis was associated with increased 12-month mortality (hazard ratio 5.47; 95% confidence interval 2.42-12.35). CONCLUSIONS: Multiple measures of immunosuppression and lack of trimethoprim-sulfamethoxazole prophylaxis were associated with nocardiosis in SOT recipients. Effectiveness of prophylaxis may be related to trimethoprim-sulfamethoxazole dose or frequency. Trimethoprim-sulfamethoxazole should be preferentially utilized over alternative agents in SOT recipients with augmented immunosuppression or signs of heightened immunocompromise.

Species designation of streptococci causing infective endocarditis in patients with mitral valve prolapse.

OBJECTIVES: Viridans group streptococci (VGS) have been previously linked to infective endocarditis (IE) in patients with mitral valve prolapse (MVP). The species identification of VGS is now available in clinical laboratories; however, it has not been examined in MVP IE. Therefore, we detailed the clinical profile, species designations, and antibiotic susceptibility of VGS isolates from patients with MVP IE. METHODS: We retrospectively queried all adults with MVP and a definite or possible IE diagnosis seen at medical centers of the Mayo Clinic Enterprise from January 2009 to December 2021. Data, including clinical characteristics, comorbidities, microbiology, and outcomes, were extracted from electronic health records. VGS isolates from patients with MVP and IE were subclassified into mutans, salivarius, anginosus, sanguinis, and mitis groups. RESULTS: A total of 38 patients with MVP with IE due to streptococcal species were included. Overall, median age was 62.4 years and 32% of patients were females. The most prevalent comorbidities were diabetes mellitus (26%), hypertension (21%), heart failure (16%), and malignancy (16%). A total of (37%) patients presented with an embolic event at the time of their IE diagnosis, 27 (66%) required valve surgery, and no patient died within the hospital stay. The Streptococcus mitis group was the predominant (n = 17, 45%) species designation; S. anginosus and S. sanguinis were identified in three (8%) each; S. mutans in two (5%); and S. salivarius in one (3%). Non-VGS streptococcal pathogens included S. agalactiae in three patients (8%), S. equi in two (5%), and S. dysgalactiae and S. bovis in one each (3%). VGS were identified in five (13%) patients, but species designation was not done. No penicillin resistance was identified among the isolates. CONCLUSION: The S. mitis group was the predominant species in our investigation. Continued evaluation of VGS species should be considered to profile the IE risk based on species identification.

Association of Neutralizing Antispike Monoclonal Antibody Treatment With Coronavirus Disease 2019 Hospitalization and Assessment of the Monoclonal Antibody Screening Score.

Objective: To test the hypothesis that the Monoclonal Antibody Screening Score performs consistently better in identifying the need for monoclonal antibody infusion throughout each "wave" of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant predominance during the coronavirus disease 2019 (COVID-19) pandemic and that the infusion of contemporary monoclonal antibody treatments is associated with a lower risk of hospitalization. Patients and Methods: In this retrospective cohort study, we evaluated the efficacy of monoclonal antibody treatment compared with that of no monoclonal antibody treatment in symptomatic adults who tested positive for SARS-CoV-2 regardless of their risk factors for disease progression or vaccination status during different periods of SARS-CoV-2 variant predominance. The primary outcome was hospitalization within 28 days after COVID-19 diagnosis. The study was conducted on patients with a diagnosis of COVID-19 from November 19, 2020, through May 12, 2022. Results: Of the included 118,936 eligible patients, hospitalization within 28 days of COVID-19 diagnosis occurred in 2.52% (456/18,090) of patients who received monoclonal antibody treatment and 6.98% (7,037/100,846) of patients who did not. Treatment with monoclonal antibody therapies was associated with a lower risk of hospitalization when using stratified data analytics, propensity scoring, and regression and machine learning models with and without adjustments for putative confounding variables, such as advanced age and coexisting medical conditions (eg, relative risk, 0.15; 95% CI, 0.14-0.17). Conclusion: Among patients with mild to moderate COVID-19, including those who have been vaccinated, monoclonal antibody treatment was associated with a lower risk of hospital admission during each wave of the COVID-19 pandemic.

Risk Factors and Outcomes of Nocardiosis in Hematopoietic Stem Cell Transplantation Recipients.

Nocardiosis occurs in up to 1.7% of hematopoietic stem cell transplantation (HSCT) recipients. Risk factors for its development and subsequent outcomes have been incompletely studied. The present study evaluated risk factors for nocardiosis in HSCT recipients and an association with 12-month mortality following Nocardia infection. We performed a nested case-control study of HSCT recipients at 3 transplantation centers between 2011 and 2021. Allogeneic HSCT recipients were matched 1:4 to controls based on age, sex, date of transplantation, and transplantation site. Because of theorized differences in the risk for nocardiosis between allogeneic HSCT recipients and autologous HSCT recipients and a low number of infected autologous HSCT recipients, only allogeneic HSCT recipients were matched to controls. Associations with nocardiosis in the allogeneic group were assessed by multivariable conditional logistic regression. Outcomes of all HSCT recipients with nocardiosis included 12-month mortality and post-treatment recurrence. Twenty-seven HSCT recipients were diagnosed with nocardiosis, including 20 allogeneic HSCT recipients and 7 autologous HSCT recipients. Twenty (74.1%) had localized pulmonary infection, 4 (14.8%) had disseminated infection, and 3 (11.1%) had localized skin infection. The allogeneic recipients were diagnosed at a median of 12.2 months after transplantation, compared with 41 months for the autologous recipients. All autologous HSCT recipients had alternative reasons for ongoing immunosuppression at diagnosis, most frequently therapy for relapsed hematologic disease. No infected patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. In multivariable analysis of 20 allogeneic patients and 80 matched controls, graft-versus-host disease (GVHD) requiring current immunosuppression and lack of prophylaxis were associated with nocardiosis. Nocardiosis was significantly associated with subsequent mortality, with a 12-month mortality rate of 29.6%; however, no patients who completed treatment experienced Nocardia recurrence. OUR DATA INDICATE THAT: intensified immunosuppression following allogeneic HSCT, such as treatment for GVHD, is associated with the development of nocardiosis. Nocardiosis occurs more distantly from transplantation in autologous recipients, possibly driven by therapy for relapsed hematologic disease. No patients receiving TMP-SMX prophylaxis developed nocardiosis. Nocardia infection is associated with high mortality, and further strategies for prevention and treatment are needed.

Outcomes of Nocardiosis and Treatment of Disseminated Infection in Solid Organ Transplant Recipients.

BACKGROUND: Nocardia is an environmental pathogen with a predilection for causing opportunistic infections in immunocompromised patients, including solid organ transplant (SOT) recipients. Although risk factors have been identified for developing nocardiosis in this population, little is known regarding clinical factors resulting in poor outcomes. We evaluated a cohort of SOT recipients with nocardiosis for associations with 12-month mortality. METHODS: We performed a multicenter retrospective cohort study of adult SOT recipients diagnosed with culture-confirmed nocardiosis from 2000 to 2020. Patients were followed for 12 months after diagnosis, unless abbreviated by mortality. Multivariable Cox regression was performed to analyze associations with 12-month mortality. A subgroup analysis of patients with disseminated nocardiosis was performed to analyze treatment variables. RESULTS: A total of 125 SOT recipients met inclusion criteria; 12-month mortality was 16.8%. Liver transplantation (hazard ratio [HR] 3.52; 95% confidence interval [CI] 1.27-9.76) and time from symptom onset to presentation (HR 0.92/d; 95% CI 0.86-0.99) were independently associated with 12-month mortality, whereas disseminated infection was not (HR 1.23; 95% CI 0.49-3.13). No treatment-specific factors were significantly associated with mortality in 33 patients with disseminated nocardiosis, although survivors had a higher rate of linezolid use. CONCLUSIONS: This study identified 2 independent associations with 12-month mortality, representing demographics and infection severity. Disseminated infection was not independently associated with poor outcomes, and specific sites of infection may be more important than dissemination itself. No treatment-specific factors were associated with mortality, though this analysis was likely underpowered. Further study of treatment strategies based on specific Nocardia syndromes is warranted.

Surgical site infections during the COVID-19 era: A retrospective, multicenter analysis.

BACKGROUND: Surgical site infections (SSIs) are an undesired perioperative outcome. Recent studies have shown increases in hospital acquired infections during the coronavirus disease 2019 (COVID-19) pandemic. The objective of this study was to evaluate postoperative SSIs in the COVID-19-era compared to a historical cohort at a large, multicenter, academic institution. METHODS: A retrospective review of all patients who underwent National Health and Safety Network (NHSN) inpatient surgical procedures between January 1, 2018 and December 31, 2020. Patients from the COVID-19-era (March-December 2020) were compared and matched 1:1 with historical controls (2018/2019) utilizing the standardized infection ratio (SIR) to detect difference. RESULTS/DISCUSSION: During the study period, 29,904 patients underwent NHSN procedures at our institution. When patients from the matched cohort (2018/2019) were compared to the COVID-19-era cohort (2020), a decreased risk of SSI was observed following colorectal surgery (RR = 0.94, 95% CI [0.65, 1.37], P = .76), hysterectomy (RR = 0.88, 95% CI [0.39, 1.99], P = .75), and knee prothesis surgery (RR = 0.95, 95% CI [0.52, 1.74], P = .88), though not statistically significant. An increased risk of SSI was observed following hip prosthesis surgery (RR 1.09, 95% CI [0.68, 1.75], P = .72), though not statistically significant. CONCLUSIONS: The risk of SSI in patients who underwent NHSN inpatient surgical procedures in 2020 with perioperative COVID-19 precautions was not significantly different when compared to matched controls at our large, multicenter, academic institution.

Effectiveness of an electronic health system-based best-practice advisory to enhance the time to de-escalation of vancomycin for respiratory indications.

Objective: Methicillin-resistant Staphylococcus aureus (MRSA) infection is highly unlikely when nasal-swab results are negative. We evaluated the impact of an electronic prompt regarding MRSA nasal screening on the length of vancomycin therapy for respiratory indications. Design: Retrospective, single-center cohort study. Setting: Tertiary-care academic medical center (Mayo Clinic) in Jacksonville, Florida. Patients: Eligible patients received empiric treatment with vancomycin for suspected or confirmed respiratory infections from January through April 2019 (preimplementation cohort) and from October 2019 through January 2020 (postimplementation cohort). Intervention: The electronic health system software was modified to provide a best-practice advisory (BPA) prompt to the pharmacist upon order verification of vancomycin for patients with suspected or confirmed respiratory indications. Pharmacists were prompted to order a MRSA nasal swab if it was not already ordered by the provider. Methods: We reviewed patient records to determine the time from vancomycin prescription to de-escalation. The secondary end point was incidence of acute kidney injury. Results: The study included 120 patients (preimplementation, n = 61; postimplementation, n = 59). Median time to de-escalation was significantly shorter for the postimplementation cohort: 76 hours (interquartile range [IQR], 52-109) versus 42 hours (IQR, 37-61; P = .002). Acute kidney injury occurred in 11 patients (18%) in the preimplementation cohort and in 3 patients (5%) in the postimplementation cohort (P = .01; number needed to treat, 8). Conclusions: Implementation of a BPA notification for MRSA nasal screening helped decrease the time to de-escalation of vancomycin.

Neurocognitive screening in patients following SARS-CoV-2 infection: tools for triage.

BACKGROUND: Cognitive complaints are common in patients recovering from Coronavirus Disease 2019 (COVID-19), yet their etiology is often unclear. We assess factors that contribute to cognitive impairment in ambulatory versus hospitalized patients during the sub-acute stage of recovery. METHODS: In this cross-sectional study, participants were prospectively recruited from a hospital-wide registry. All patients tested positive for SARS-CoV-2 infection using a real-time reverse transcriptase polymerase-chain-reaction assay. Patients ≤ 18 years-of-age and those with a pre-existing major neurocognitive disorder were excluded. Participants completed an extensive neuropsychological questionnaire and a computerized cognitive screen via remote telemedicine platform. Rates of subjective and objective neuropsychological impairment were compared between the ambulatory and hospitalized groups. Factors associated with impairment were explored separately within each group. RESULTS: A total of 102 patients (76 ambulatory, 26 hospitalized) completed the symptom inventory and neurocognitive tests 24 ± 22 days following laboratory confirmation of SARS-CoV-2 infection. Hospitalized and ambulatory patients self-reported high rates of cognitive impairment (27-40%), without differences between the groups. However, hospitalized patients showed higher rates of objective impairment in visual memory (30% vs. 4%; p = 0.001) and psychomotor speed (41% vs. 15%; p = 0.008). Objective cognitive test performance was associated with anxiety, depression, fatigue, and pain in the ambulatory but not the hospitalized group. CONCLUSIONS: Focal cognitive deficits are more common in hospitalized than ambulatory patients. Cognitive performance is associated with neuropsychiatric symptoms in ambulatory but not hospitalized patients. Objective neurocognitive measures can provide essential information to inform neurologic triage and should be included as endpoints in clinical trials.

Clinical Characteristics and Outcomes of Patients With SARS-CoV-2 Reinfection.

Objective: To examine the clinical characteristics, risk of hospitalization, and mortality of patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. Patients and Methods: We retrospectively reviewed all patients with SARS-CoV-2 reinfection at all Mayo Clinic sites between May 23, 2020, and June 30, 2021 (the period before the emergence of the Delta variant in the United States). The reinfection was defined as a positive SARS-CoV-2 test more than or equal to 90 days after initial infection or 45-89 days after with symptomatic second episode. Vaccination status was classified as fully vaccinated, first dose, and unvaccinated. Comparative analysis of baseline characteristics and comorbidities was performed by hospitalization and vaccination status. The survival analysis of the hospitalized patients was performed using Cox proportional hazard regression. Results: Among the 554 patients reinfected with SARS-CoV-2, 59 (10.6%) were pediatric, and 495 (89.4%) were adults. The median age was 13.9 years (interquartile range, 8.5-16.5 years) for the pediatric and 50.2 years (interquartile range, 28.4-65.6 years) for the adult population. Among the adult patients, the majority were unvaccinated (83.4%, n=413), and the duration to reinfection from initial infection was the longest in the fully vaccinated group (P<.001). Forty-two (75%) out of 56 patients were seropositive within 7 days of reinfection. In hospitalized adult patients, Charlson Comorbidity Index was an independent risk factor for mortality (adjusted hazard ratio, 0.35; 95% CI, 0.19-0.51). Conclusion: In this study, most adult patients with SARS-CoV-2 reinfection were unvaccinated. Furthermore, the duration to reinfection was longest in fully vaccinated individuals. Seropositivity was common among adult patients.

Clinical and laboratory profiles of the SARS-CoV-2 Delta variant compared with pre-Delta variants.

OBJECTIVES: The emergence of SARS-CoV-2 variants of concern has led to significant phenotypical changes in transmissibility, virulence, and public health measures. Our study used clinical data to compare characteristics between a Delta variant wave and a pre-Delta variant wave of hospitalized patients. METHODS: This single-center retrospective study defined a wave as an increasing number of COVID-19 hospitalizations, which peaked and later decreased. Data from the United States Department of Health and Human Services were used to identify the waves' primary variant. Wave 1 (August 8, 2020-April 1, 2021) was characterized by heterogeneous variants, whereas Wave 2 (June 26, 2021-October 18, 2021) was predominantly the Delta variant. Descriptive statistics, regression techniques, and machine learning approaches supported the comparisons between waves. RESULTS: From the cohort (N = 1318), Wave 2 patients (n = 665) were more likely to be younger, have fewer comorbidities, require more care in the intensive care unit, and show an inflammatory profile with higher C-reactive protein, lactate dehydrogenase, ferritin, fibrinogen, prothrombin time, activated thromboplastin time, and international normalized ratio compared with Wave 1 patients (n = 653). The gradient boosting model showed an area under the receiver operating characteristic curve of 0.854 (sensitivity 86.4%; specificity 61.5%; positive predictive value 73.8%; negative predictive value 78.3%). CONCLUSION: Clinical and laboratory characteristics can be used to estimate the COVID-19 variant regardless of genomic testing availability. This finding has implications for variant-driven treatment protocols and further research.

Low antispike antibody levels correlate with poor outcomes in COVID-19 breakthrough hospitalizations.

BACKGROUND: While COVID-19 immunization programs attempted to reach targeted rates, cases rose significantly since the emergence of the delta variant. This retrospective cohort study describes the correlation between antispike antibodies and outcomes of hospitalized, breakthrough cases during the delta variant surge. METHODS: All patients with positive SARS-CoV-2 polymerase chain reaction hospitalized at Mayo Clinic Florida from 19 June 2021 to 11 November 2021 were considered for analysis. Cases were analyzed by vaccination status. Breakthrough cases were then analyzed by low and high antibody titers against SARS-CoV-2 spike protein, with a cut-off value of ≥132 U/ml. Outcomes included hospital length of stay (LOS), need for intensive care unit (ICU), mechanical ventilation, and mortality. We used 1:1 nearest neighbor propensity score matching without replacement to assess for confounders. RESULTS: Among 627 hospitalized patients with COVID-19, vaccine breakthrough cases were older with more comorbidities compared to unvaccinated. After propensity score matching, the unvaccinated patients had higher mortality (27 [28.4%] vs. 12 [12.6%], p = 0.002) and LOS (7 [1.0-57.0] vs. 5 [1.0-31.0] days, p = 0.011). In breakthrough cases, low-titer patients were more likely to be solid organ transplant recipients (16 [34.0%] vs. 9 [12.3%], p = 0.006), with higher need for ICU care (24 [51.1%] vs. 22 [11.0%], p = 0.034), longer hospital LOS (median 6 vs. 5 days, p = 0.013), and higher mortality (10 [21.3%] vs. 5 [6.8%], p = 0.025) than high-titer patients. CONCLUSIONS: Hospitalized breakthrough cases were more likely to have underlying risk factors than unvaccinated patients. Low-spike antibody titers may serve as an indicator for poor prognosis in breakthrough cases admitted to the hospital.

Neurocognitive Screening in Patients Following SARS-CoV-2 Infection: Tools for Triage.

Background and purpose Cognitive complaints are common in patients recovering from Coronavirus Disease 2019 (COVID-19), yet their etiology is often unclear. We assess factors that contribute to cognitive impairment in ambulatory versus hospitalized patients during the sub-acute stage of recovery. Methods Participants were prospectively recruited from a hospital-wide registry. All patients tested positive for SARS-CoV-2 infection using a real-time reverse transcriptase polymerasechain-reaction assay. Patients ≤ 18 years-of-age and those with a pre-existing major neurocognitive disorder were excluded. Participants completed an extensive neuropsychological questionnaire and a computerized cognitive screen via remote telemedicine platform. Rates of subjective and objective neuropsychological impairment were compared between the ambulatory and hospitalized groups. Factors associated with impairment were explored separately within each group. Results A total of 102 patients (76 ambulatory, 26 hospitalized) completed the symptom inventory and neurocognitive tests 24 ± 22 days following laboratory confirmation of SARSCoV-2 infection. Hospitalized and ambulatory patients self-reported high rates of cognitive impairment (27-40%), without differences between the groups. However, hospitalized patients showed higher rates of objective impairment in visual memory (30% vs. 4%; p=0.001) and psychomotor speed (41% vs. 15%; p=0.008). Objective cognitive test performance was associated with anxiety, depression, fatigue, and pain in the ambulatory but not the hospitalized group. Conclusions Focal cognitive deficits are more common in hospitalized than ambulatory patients. Cognitive performance is associated with neuropsychiatric symptoms in ambulatory but not hospitalized patients. Objective neurocognitive measures can provide essential information to inform neurologic triage and should be included as endpoints in clinical trials.

Effectiveness of Monoclonal Antibodies in Preventing Severe COVID-19 With Emergence of the Delta Variant.

Anti-spike monoclonal antibodies have proven invaluable in preventing severe outcomes from COVID-19, including hospitalization and death. The rise of the SARS-CoV-2 delta variant begs the question of whether monoclonal antibodies maintain similar efficacy now as they had when the alpha and beta variants predominated, when they were first assessed and approved. We used a retrospective cohort to compare rates of severe outcomes in an epoch in which alpha and beta were predominant compared with delta. A total of 5356 patients were infused during the alpha/beta variant-predominant (n=4874) and delta variant-predominant (n=482) era. Overall, odds of severe infection were 3.0% of patients in the alpha/beta-predominant era compared with 4.9% in the delta-predominant cohort. The unadjusted odds ratio (OR) was higher for severe disease in the delta era (OR, 1.67; 95% CI, 0.96 to 2.89), particularly when adjusted for Charlson Comorbidity Index (adjusted OR, 2.04; 95% CI, 1.30 to 3.08). The higher odds of severe infection could be due to a more virulent delta variant, although the possibility of decreased anti-spike monoclonal antibody effectiveness in the clinical setting cannot be excluded. Research into the most effective strategies for using and improving anti-spike monoclonals for the treatment of emerging variants is warranted.