The COVID-19 epidemic of 2019–20 is due to the novel coronavirus SARS-CoV-2. Following first case description in December, 2019 this virus has infected over 10 million individuals and resulted in at least 500,000 deaths world-wide. The virus is undergoing rapid mutation, with two major clades of sequence variants emerging. This study sought to determine whether SARS-CoV-2 sequence variants are associated with differing outcomes among COVID-19 patients in a single medical system. Whole genome SARS-CoV-2 RNA sequence was obtained from isolates collected from patients registered in the University of Washington Medicine health system between March 1 and April 15, 2020. Demographic and baseline clinical characteristics of patients and their outcome data including their hospitalization and death were collected. Statistical and machine learning models were applied to determine if viral genetic variants were associated with specific outcomes of hospitalization or death. Full length SARS-CoV-2 sequence was obtained 190 subjects with clinical outcome data. 35 (18.4%) were hospitalized and 14 (7.4%) died from complications of infection. A total of 289 single nucleotide variants were identified. Clustering methods demonstrated two major viral clades, which could be readily distinguished by 12 polymorphisms in 5 genes. A trend toward higher rates of hospitalization of patients with Clade 2 infections was observed (p = 0.06, Fisher’s exact). Machine learning models utilizing patient demographics and co-morbidities achieved area-under-the-curve (AUC) values of 0.93 for predicting hospitalization. Addition of viral clade or sequence information did not significantly improve models for outcome prediction. In summary, SARS-CoV-2 shows substantial sequence diversity in a community-based sample. Two dominant clades of virus are in circulation. Among patients sufficiently ill to warrant testing for virus, no significant difference in outcomes of hospitalization or death could be discerned between clades in this sample. Major risk factors for hospitalization and death for either major clade of virus include patient age and comorbid conditions.
BACKGROUND Necrotizing soft tissue infections (NSTI) represent a heterogeneous group of rapidly progressive skin and soft tissue infections associated with significant morbidity and mortality. Efforts to identify factors associated with death have produced mixed results, and little or no data is available for other adverse outcomes. We sought to determine whether admission variables were associated with mortality, limb loss, and discharge disposition in patients with NSTI. METHODS We analyzed prospectively collected data of adult patients with surgically confirmed NSTI from an NSTI registry maintained at a quaternary referral center. Factors independently associated with mortality, amputation, and skilled nursing facility discharge were identified using logistic regression. RESULTS Between 2015 and 2018, 446 patients were identified. The median age was 55 years (interquartile range, 43–62). The majority of patients were male (65%), white (77%), and transferred from another facility (90%). The perineum was most commonly involved (37%), followed by the lower extremity (34%). The median number of operative debridements was 3 (interquartile range, 2–4). Overall mortality was 15%, and 21% of extremity NSTI patients required amputation. Age greater than 60 years; creatinine greater than 2 mg/dL; white blood cell count greater than 30 x 10^3 /μl, platelets less than 150 × 103/μL, and clostridial involvement were independently associated with greater odds of death; perineal involvement was associated with lower odds of death. Age greater than 60 years; sex, male; nonwhite race; diabetes; chronic wound as etiology; leg involvement; transfer status; and sodium, less than 130 mEq/L were independently associated with amputation. Age greater than 60 years; sex, female; nonwhite race; perineal involvement; and amputation were associated with skilled care facility discharge. CONCLUSION Necrotizing soft tissue infections are a heterogeneous group of infections involving significantly different patient populations with different outcomes; efforts to differentiate and predict adverse outcomes in NSTI should include laboratory data, comorbidities, infection site, and/or etiology to improve predictions and better account for this heterogeneity. LEVEL OF EVIDENCE Prognostic, Level III.
Background β-Hemolytic streptococci are frequently implicated in necrotizing soft-tissue infections (NSTIs). Clindamycin administration may improve outcomes in patients with serious streptococcal infections. However, clindamycin resistance is growing worldwide, and resistance patterns in NSTIs and their impact on outcomes are unknown. Methods Between 2015 and 2018, patients with NSTI at a quaternary referral center were followed up for the outcomes of death, limb loss, and streptococcal toxic shock syndrome. Surgical wound cultures and resistance data were obtained within 48 hours of admission as part of routine care. Risk ratios for the association between these outcomes and the presence of β-hemolytic streptococci or clindamycin-resistant β-hemolytic streptococci were calculated using log-binomial regression, controlling for age, transfer status, and injection drug use–related etiology. Results Of 445 NSTIs identified, 85% had surgical wound cultures within 48 hours of admission. β-Hemolytic streptococci grew in 31%, and clindamycin resistance was observed in 31% of cultures. The presence of β-hemolytic streptococci was associated with greater risk of amputation (risk ratio, 1.80; 95% confidence interval, 1.07–3.01), as was the presence of clindamycin resistance among β-hemolytic streptococci infections (1.86; 1.10–3.16). Conclusions β-Hemolytic streptococci are highly prevalent in NSTIs, and in our population clindamycin resistance was more common than previously described. Greater risk of limb loss among patients with β-hemolytic streptococci—particularly clindamycin-resistant strains—may portend a more locally aggressive disease process or may represent preexisting patient characteristics that predispose to both infection and limb loss. Regardless, these findings may inform antibiotic selection and surgical management to maximize the potential for limb salvage.
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