Successful Treatment of Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Patients With Immunodeficiency With Extended Nirmatrelvir/Ritonavir: Case Series.

Immunocompromised patients with B-cell deficiencies are at risk for prolonged symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We describe 4 patients treated for B-cell malignancies with B-cell-depleting therapies who developed persistent SARS-CoV-2 infection and had resolution of symptoms following an extended course of nirmatrelvir/ritonavir.

Risk factors and outcomes associated with community-onset and hospital-acquired coinfection in patients hospitalized for coronavirus disease 2019 (COVID-19): A multihospital cohort study.

BACKGROUND: We sought to determine the incidence of community-onset and hospital-acquired coinfection in patients hospitalized with coronavirus disease 2019 (COVID-19) and to evaluate associated predictors and outcomes. METHODS: In this multicenter retrospective cohort study of patients hospitalized for COVID-19 from March 2020 to August 2020 across 38 Michigan hospitals, we assessed prevalence, predictors, and outcomes of community-onset and hospital-acquired coinfections. In-hospital and 60-day mortality, readmission, discharge to long-term care facility (LTCF), and mechanical ventilation duration were assessed for patients with versus without coinfection. RESULTS: Of 2,205 patients with COVID-19, 141 (6.4%) had a coinfection: 3.0% community onset and 3.4% hospital acquired. Of patients without coinfection, 64.9% received antibiotics. Community-onset coinfection predictors included admission from an LTCF (OR, 3.98; 95% CI, 2.34-6.76; P < .001) and admission to intensive care (OR, 4.34; 95% CI, 2.87-6.55; P < .001). Hospital-acquired coinfection predictors included fever (OR, 2.46; 95% CI, 1.15-5.27; P = .02) and advanced respiratory support (OR, 40.72; 95% CI, 13.49-122.93; P < .001). Patients with (vs without) community-onset coinfection had longer mechanical ventilation (OR, 3.31; 95% CI, 1.67-6.56; P = .001) and higher in-hospital mortality (OR, 1.90; 95% CI, 1.06-3.40; P = .03) and 60-day mortality (OR, 1.86; 95% CI, 1.05-3.29; P = .03). Patients with (vs without) hospital-acquired coinfection had higher discharge to LTCF (OR, 8.48; 95% CI, 3.30-21.76; P < .001), in-hospital mortality (OR, 4.17; 95% CI, 2.37-7.33; P ≤ .001), and 60-day mortality (OR, 3.66; 95% CI, 2.11-6.33; P ≤ .001). CONCLUSION: Despite community-onset and hospital-acquired coinfection being uncommon, most patients hospitalized with COVID-19 received antibiotics. Admission from LTCF and to ICU were associated with increased risk of community-onset coinfection. Future studies should prospectively validate predictors of COVID-19 coinfection to facilitate the reduction of antibiotic use.

Monoclonal Antibodies for Early Treatment of COVID-19 in a World of Evolving SARS-CoV-2 Mutations and Variants.

Monoclonal antibodies targeting the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 spike protein are important outpatient treatment options in coronavirus disease 2019 to mitigate progression of disease and prevent hospitalization. The impact of different RBD mutations on the efficacy of the available monoclonal antibodies and processes for incorporating this impact into treatment algorithms are ill defined. Herein, we synthesize the data surrounding the impact of key RBD mutations on the efficacy of US Food and Drug Administration Emergency Use Authorized monoclonal antibodies and describe our approach at Michigan Medicine at monitoring mutation frequency in circulating virus and developing an algorithm that incorporates these data into outpatient treatment pathways.

Empiric Antibacterial Therapy and Community-onset Bacterial Coinfection in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19): A Multi-hospital Cohort Study.

BACKGROUND: Antibacterials may be initiated out of concern for bacterial coinfection in coronavirus disease 2019 (COVID-19). We determined prevalence and predictors of empiric antibacterial therapy and community-onset bacterial coinfections in hospitalized patients with COVID-19. METHODS: A randomly sampled cohort of 1705 patients hospitalized with COVID-19 in 38 Michigan hospitals between 3/13/2020 and 6/18/2020. Data were collected on early (within 2 days of hospitalization) empiric antibacterial therapy and community-onset bacterial coinfections (positive microbiologic test ≤3 days). Poisson generalized estimating equation models were used to assess predictors. RESULTS: Of 1705 patients with COVID-19, 56.6% were prescribed early empiric antibacterial therapy; 3.5% (59/1705) had a confirmed community-onset bacterial infection. Across hospitals, early empiric antibacterial use varied from 27% to 84%. Patients were more likely to receive early empiric antibacterial therapy if they were older (adjusted rate ratio [ARR]: 1.04 [1.00-1.08] per 10 years); had a lower body mass index (ARR: 0.99 [0.99-1.00] per kg/m2), more severe illness (eg, severe sepsis; ARR: 1.16 [1.07-1.27]), a lobar infiltrate (ARR: 1.21 [1.04-1.42]); or were admitted to a for-profit hospital (ARR: 1.30 [1.15-1.47]). Over time, COVID-19 test turnaround time (returned ≤1 day in March [54.2%, 461/850] vs April [85.2%, 628/737], P < .001) and empiric antibacterial use (ARR: 0.71 [0.63-0.81] April vs March) decreased. CONCLUSIONS: The prevalence of confirmed community-onset bacterial coinfections was low. Despite this, half of patients received early empiric antibacterial therapy. Antibacterial use varied widely by hospital. Reducing COVID-19 test turnaround time and supporting stewardship could improve antibacterial use.

Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW). RESULTS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia. CONCLUSIONS: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.