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.

Paediatric safety assessment of BNT162b2 vaccination in a multistate hospital-based electronic health record system in the USA: a retrospective analysis.

BACKGROUND: The emergency use authorisation of BNT162b2 (tozinameran; Comirnaty, Pfizer-BioNTech) for children aged 5-17 years has resulted in rapid vaccination in the paediatric population. However, there are few studies of adverse events associated with vaccination in children. The aim of this study was to systematically assess the adverse events of two-dose BNT162b2 vaccination in the paediatric population. METHODS: We conducted a retrospective analysis of patient electronic health records (EHRs) of children aged 5-17 years who received the primary two-dose series of the BNT162b2 vaccine between Jan 5, 2021, and Aug 5, 2022, at the Mayo Clinic Health System (MN, FL, AZ, IA, and WI), USA. Using natural language processing, we automatically curated adverse events reported by physicians in EHR clinical notes before and after vaccination. To determine significant adverse events after BNT162b2 vaccination, we calculated risk differences, which was defined as the percentage difference between the rate of children with an adverse event after a vaccine dose and the baseline rate of children with an adverse event before vaccination. 95% CIs and p values were calculated using the Miettinen and Nurminen score method. FINDINGS: 56 436 individuals aged 5-17 years (20 227 aged 5-11 years and 36 209 aged 12-17 years) with EHRs in the Mayo Clinic Health Systems were included in the study. Overall, the reporting of adverse events remained low in passive surveillance. Serious adverse events were rare after the first and second doses of BNT162b2, with rates of anaphylaxis (six [0·01%] of 56 436), myocarditis (five [0·01%]), and pericarditis (three [0·01%]) consistent with previous studies. Among the 20 227 5-11-year-olds, there were increased risks of fatigue (58 after second dose vs 41 before first dose; risk difference [RD]dose2 0·08% [95% CI -0·01 to 0·18], p=0·044) and fever (104 after second dose vs 77 before first dose; RDdose2 0·13% [0·00 to 0·27], p=0·022) after the second dose. Among the 36 209 12-17-year-olds, there were increased risks of arthralgia (69 after second dose vs 48 before first dose; RDdose2 0·06% [-0·00 to 0·12], p=0·026), chills (58 after second dose vs 40 before first dose; RDdose2 0·05% [-0·00 to 0·11], p=0·034), and myalgia (96 after second dose vs 73 before first dose; RDdose2 0·06% [-0·01 to 0·14], p=0·038) after the second dose. Although the overall incidence was low, there was an increased risk of myocarditis in males aged 12-17 years after the second dose (five after second dose vs zero before first dose; RDdose2 0·03% [0·01 to 0·07], p=0·013), with median age being 15 years (IQR 14 to 16). INTERPRETATION: Overall, this data suggests that vaccination with BNT162b2 in the paediatric population is generally safe and well-tolerated. Further research is warranted to investigate the basis for the increased risk of myocarditis in adolescent males. Additionally, further studies are needed to confirm whether the findings in our study population apply to the whole vaccinated paediatric population. FUNDING: nference.

COVID-19 in patients with B cell immune deficiency.

This article aims to describe the clinical manifestations and management of COVID-19 in patients with primary and secondary B cell deficient states. We describe the epidemiologic and clinical features as well as unique management paradigm including isolation precautions with COVID-19. We then focus upon primary and secondary preventive approaches including vaccination and pre- as well as post-exposure prophylaxis. Further, we elaborate upon the important disease specific risk factors in these patients and the need to conduct prospective clinical trials to develop individualized management strategies in this population.

Rebound Phenomenon after Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease-2019 in High-Risk Persons.

In a cohort of 483 high-risk patients treated with nirmatrelvir/ritonavir for coronavirus disease-2019, two patients (0.4%) required hospitalization by day 30. Four patients (0.8%) experienced rebound of symptoms, which were generally mild, at median of 9 days after treatment, and all resolved without additional COVID-19-directed therapy.

Durability analysis of the highly effective mRNA-1273 vaccine against COVID-19.

COVID-19 vaccines are effective, but breakthrough infections have been increasingly reported. We conducted a test-negative case-control study to assess the durability of protection against symptomatic infection after vaccination with mRNA-1273. We fit conditional logistic regression (CLR) models stratified on residential county and calendar date of SARS-CoV-2 PCR testing to assess the association between the time elapsed since vaccination and the odds of symptomatic infection, adjusted for several covariates. There were 2,364 symptomatic individuals who had a positive SARS-CoV-2 PCR test after full vaccination with mRNA-1273 ("cases") and 12,949 symptomatic individuals who contributed 15,087 negative tests after full vaccination ("controls"). The odds of symptomatic infection were significantly higher 250 days after full vaccination compared to the date of full vaccination (Odds Ratio [OR]: 2.47, 95% confidence interval [CI]: 1.19-5.13). The odds of non-COVID-19 associated hospitalization and non-COVID-19 pneumonia (negative control outcomes) remained relatively stable over the same time interval (Day 250 ORNon-COVID Hospitalization: 0.68, 95% CI: 0.47-1.0; Day 250 ORNon-COVID Pneumonia: 1.11, 95% CI: 0.24-5.2). The odds of symptomatic infection remained significantly lower almost 300 days after the first mRNA-1273 dose as compared to 4 days after the first dose, when immune protection approximates the unvaccinated state (OR: 0.26, 95% CI: 0.17-0.39). Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. In summary, mRNA-1273 robustly protected against symptomatic SARS-CoV-2 infection at least 8 months after full vaccination, but the degree of protection waned over this time period.

Third dose vaccination with mRNA-1273 or BNT162b2 vaccines improves protection against SARS-CoV-2 infection.

As of 2021 November 29, booster vaccination against SARS-CoV-2 infection has been recommended for all individuals aged 18 years and older in the United States. A key reason for this recommendation is the expectation that a booster vaccine dose can alleviate observed waning of vaccine effectiveness (VE). Although initial reports of booster effectiveness have been positive, the level of protection from booster vaccination is unclear. We conducted two studies to assess the impact of booster vaccination, with BNT162b2 or mRNA-1273, on the incidence of SARS-CoV-2 infection between August and December 2021. We first compared SARS-CoV-2 infection incidence in cohorts of 3-dose vaccine recipients to incidence in matched cohorts of 2-dose vaccine recipients (cohort size = 24,539 for BNT162b2 and 14,004 for mRNA-1273). Additionally, we applied a test-negative study design to compare the level of protection against symptomatic infection in 3-dose recipients to that observed in recent 2-dose primary vaccine series recipients. The 3-dose recipients experienced a significantly lower incidence rate of SARS-CoV-2 infection than the matched 2-dose cohorts (BNT162b2 Incidence Rate Ratio: 0.11, 95% CI: 0.09 to 0.13 and mRNA-1273 IRR: 0.11, 95% CI: 0.08 to 0.15). Results from the test-negative study showed the third vaccine dose mitigated waning of VE, with the risk of symptomatic infection in 3-dose recipients being comparable to that observed 7 to 73 days after the primary vaccine series. These results show that 3-dose vaccine regimens with BNT162b2 or mRNA-1273 are effective at reducing SARS-CoV-2 infection and support the widespread administration of booster vaccine doses.

SARS-CoV-2 and influenza coinfection throughout the COVID-19 pandemic: an assessment of coinfection rates, cohort characteristics, and clinical outcomes.

Case reports of patients infected with COVID-19 and influenza virus ("flurona") have raised questions around the prevalence and severity of coinfection. Using data from HHS Protect Public Data Hub, NCBI Virus, and CDC FluView, we analyzed trends in SARS-CoV-2 and influenza hospitalized coinfection cases and strain prevalences. We also characterized coinfection cases across the Mayo Clinic Enterprise from January 2020 to April 2022. We compared expected and observed coinfection case counts across different waves of the pandemic and assessed symptoms and outcomes of coinfection and COVID-19 monoinfection cases after propensity score matching on clinically relevant baseline characteristics. From both the Mayo Clinic and nationwide datasets, the observed coinfection rate for SARS-CoV-2 and influenza has been higher during the Omicron era (2021 December 14 to 2022 April 2) compared to previous waves, but no higher than expected assuming infection rates are independent. At the Mayo Clinic, only 120 coinfection cases were observed among 197,364 SARS-CoV-2 cases. Coinfected patients were relatively young (mean age: 26.7 years) and had fewer serious comorbidities compared to monoinfected patients. While there were no significant differences in 30-day hospitalization, ICU admission, or mortality rates between coinfected and matched COVID-19 monoinfection cases, coinfection cases reported higher rates of symptoms including congestion, cough, fever/chills, headache, myalgia/arthralgia, pharyngitis, and rhinitis. While most coinfection cases observed at the Mayo Clinic occurred among relatively healthy individuals, further observation is needed to assess outcomes among subpopulations with risk factors for severe COVID-19 such as older age, obesity, and immunocompromised status.

Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants.

The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and performed whole-genome viral sequencing from 102 COVID-19 patients, including 43 vaccine breakthrough infections. We identified 92 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a 3-month window. Deletions in the Spike protein N-terminal domain were highly enriched for these 'surge-associated mutations' (Odds Ratio = 14.19, 95% CI 6.15-32.75, p value = 3.41 × 10-10). Based on a longitudinal analysis of mutational prevalence globally, we found an expanding repertoire of Spike protein deletions proximal to an antigenic supersite in the N-terminal domain that may be one of the key contributors to the evolution of highly transmissible variants. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences from 102 patients and identified 107 unique mutations, including 78 substitutions and 29 deletions. In five patients, we identified distinct deletions between residues 85-90, which reside within a linear B cell epitope. Deletions in this region arose contemporaneously on a diverse background of variants across the globe since December 2020. Overall, our findings based on genomic-epidemiology and clinical surveillance suggest that the genomic deletion of dispensable antigenic regions in SARS-CoV-2 may contribute to the evasion of immune responses and the evolution of highly transmissible variants.

Inference from longitudinal laboratory tests characterizes temporal evolution of COVID-19-associated coagulopathy (CAC).

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.

Comparable Outcomes for Bebtelovimab and Ritonavir-Boosted Nirmatrelvir Treatment in High-Risk Patients With Coronavirus Disease-2019 During Severe Acute Respiratory Syndrome Coronavirus 2 BA.2 Omicron Epoch.

The effectiveness of bebtelovimab in real-world settings has not been assessed. In this retrospective cohort study of 3607 high-risk patients, bebtelovimab was used more commonly than nirmatrelvir-ritonavir for treatment of coronavirus disease 2019 (COVID-19) among older patients, immunosuppressed patients, and those with multiple comorbid conditions. Despite its use in patients with multiple comorbid conditions, the rate of progression to severe disease after bebtelovimab (1.4% [95% confidence interval, 1.2%-1.7%]) was not significantly different from that for nirmatrelvir-ritonavir treatment (1.2% [.8%-1.5%]). Our findings support the emergency use authorization of bebtelovimab for treatment of COVID-19 during the Omicron epoch dominated by BA.2 and subvariants.

Antimicrobial prescribing practices at a tertiary-care center in patients diagnosed with COVID-19 across the continuum of care.

In a single-center review of antibiotic prescribing in COVID-19 patients, 10% of patients received antimicrobials, and inpatients encounters had the highest rate and spectrum of prescribing. Prescribing rate, spectrum, and duration appeared to increase with disease severity in inpatients. Antimicrobial prescribing in patients managed in ambulatory encounters was less common.

Real-world Clinical Outcomes of Bebtelovimab and Sotrovimab Treatment of High-risk Persons With Coronavirus Disease 2019 During the Omicron Epoch.

Background: Antispike monoclonal antibodies are recommended for early treatment of high-risk persons with mild to moderate coronavirus disease 2019 (COVID-19). However, clinical outcomes of their use during the severe acute respiratory syndrome coronavirus 2 Omicron wave are limited. Methods: This is a descriptive retrospective study of high-risk adult patients who received treatment with sotrovimab (January 1-March 20, 2022) or bebtelovimab (March 21-April 30, 2022). The primary outcome was the proportion of patients who progressed to severe outcome within 30 days after receiving antispike-neutralizing monoclonal antibody infusion. Results: A total of 3872 high-risk patients (median age, 62.7 years; 41.1% male) with mild to moderate COVID-19 received sotrovimab (n = 2182) or bebtelovimab (n = 1690). Among sotrovimab-treated patients, the most common comorbidities were an immunosuppressed condition (46.7%), hypertension (38.2%), and diabetes (21.2%). The rates of severe outcome, intensive care unit (ICU) admission, and mortality were 2.2%, 1.0%, and 0.4%, respectively, after sotrovimab infusion. Among bebtelovimab-treated patients, the most common comorbidities were hypertension (42.7%), diabetes (17.1%), and an immunosuppressed condition (17.0%). The rates of severe disease, ICU admission, and mortality were 1.3%, 0.5%, and 0.2%, respectively, after bebtelovimab infusion. Older age, immunosuppressed status, and several comorbidities were associated with severe disease progression, while COVID-19 vaccination was associated with lower risk. No anaphylaxis was reported during monoclonal antibody infusion. Conclusions: This real-world analysis of a large cohort of high-risk patients demonstrates low rates of severe disease after treatment with sotrovimab during the era dominated by Omicron B.1.1.529 and after treatment with bebtelovimab during the era dominated by BA.2 and Omicron subvariants.

Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19.

BACKGROUND: There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. OBJECTIVE: Develop evidence-based, rapid, living guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. METHODS: In March 2020, the Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise to regularly review the evidence and make recommendations about the treatment and management of persons with COVID-19. The process used a living guideline approach and followed a rapid recommendation development checklist. The panel prioritized questions and outcomes. A systematic review of the peer-reviewed and grey literature was conducted at regular intervals. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. RESULTS: Based on the most recent search conducted on May 31, 2022, the IDSA guideline panel has made 30 recommendations for the treatment and management of the following groups/populations: pre- and post-exposure prophylaxis, ambulatory with mild-to-moderate disease, hospitalized with mild-to-moderate, severe but not critical, and critical disease. As these are living guidelines, the most recent recommendations can be found online at: https://idsociety.org/COVID19guidelines. CONCLUSIONS: At the inception of its work, the panel has expressed the overarching goal that patients be recruited into ongoing trials. Since then, many trials were done which provided much needed evidence for COVID-19 therapies. There still remain many unanswered questions as the pandemic evolved which we hope future trials can answer.

Development of a multiomics model for identification of predictive biomarkers for COVID-19 severity: a retrospective cohort study.

BACKGROUND: COVID-19 is a multi-system disorder with high variability in clinical outcomes among patients who are admitted to hospital. Although some cytokines such as interleukin (IL)-6 are believed to be associated with severity, there are no early biomarkers that can reliably predict patients who are more likely to have adverse outcomes. Thus, it is crucial to discover predictive markers of serious complications. METHODS: In this retrospective cohort study, we analysed samples from 455 participants with COVID-19 who had had a positive SARS-CoV-2 RT-PCR result between April 14, 2020, and Dec 1, 2020 and who had visited one of three Mayo Clinic sites in the USA (Minnesota, Arizona, or Florida) in the same period. These participants were assigned to three subgroups depending on disease severity as defined by the WHO ordinal scale of clinical improvement (outpatient, severe, or critical). Our control cohort comprised of 182 anonymised age-matched and sex-matched plasma samples that were available from the Mayo Clinic Biorepository and banked before the COVID-19 pandemic. We did a deep profiling of circulatory cytokines and other proteins, lipids, and metabolites from both cohorts. Most patient samples were collected before, or around the time of, hospital admission, representing ideal samples for predictive biomarker discovery. We used proximity extension assays to quantify cytokines and circulatory proteins and tandem mass spectrometry to measure lipids and metabolites. Biomarker discovery was done by applying an AutoGluon-tabular classifier to a multiomics dataset, producing a stacked ensemble of cutting-edge machine learning algorithms. Global proteomics and glycoproteomics on a subset of patient samples with matched pre-COVID-19 plasma samples was also done. FINDINGS: We quantified 1463 cytokines and circulatory proteins, along with 902 lipids and 1018 metabolites. By developing a machine-learning-based prediction model, a set of 102 biomarkers, which predicted severe and clinical COVID-19 outcomes better than the traditional set of cytokines, were discovered. These predictive biomarkers included several novel cytokines and other proteins, lipids, and metabolites. For example, altered amounts of C-type lectin domain family 6 member A (CLEC6A), ether phosphatidylethanolamine (P-18:1/18:1), and 2-hydroxydecanoate, as reported here, have not previously been associated with severity in COVID-19. Patient samples with matched pre-COVID-19 plasma samples showed similar trends in muti-omics signatures along with differences in glycoproteomics profile. INTERPRETATION: A multiomic molecular signature in the plasma of patients with COVID-19 before being admitted to hospital can be exploited to predict a more severe course of disease. Machine learning approaches can be applied to highly complex and multidimensional profiling data to reveal novel signatures of clinical use. The absence of validation in an independent cohort remains a major limitation of the study. FUNDING: Eric and Wendy Schmidt.

Outcomes of bebtelovimab and sotrovimab treatment of solid organ transplant recipients with mild-to-moderate coronavirus disease 2019 during the Omicron epoch.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at high-risk for severe infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anti-spike monoclonal antibodies are currently utilized under emergency use authorization to prevent hospitalization in high-risk individuals with coronavirus disease 2019 (COVID-19), including SOTRs. However, clinical data for bebtelovimab, the sole currently available anti-spike monoclonal antibody for COVID-19, is limited. METHODS: We conducted a retrospective cohort study of adult SOTRs diagnosed with mild-to-moderate COVID-19 from January 2022 through May 2022 who received either bebtelovimab or sotrovimab. The primary outcome was COVID-19-related hospitalization within 30 days of COVID-19 diagnosis. Data were analyzed with Fisher's exact test. RESULTS: Among 361 SOTRs, 92 (25.5%) received bebtelovimab and 269 (74.5%) received sotrovimab. The most common organ transplant was a kidney (42.4%). SOTRs who received bebtelovimab had a higher proportion who had received a booster SARS-CoV-2 vaccine dose and had received their last vaccination dose more recently. Eleven (3.0%) SOTRs were hospitalized, and rates of hospitalization were similar between monoclonal antibody groups (3.3% versus 3.0%; p > .99). Three patients required admission to an intensive care unit, all of who received sotrovimab. Four (1.1%) patients died within 30 days of COVID-19 diagnosis, two from each group. CONCLUSIONS: SOTRs with mild-to-moderate COVID-19 who received bebtelovimab had similar rates of COVID-19-related hospitalization as those who received sotrovimab. While differences in vaccination rates and viral subvariants could act as confounders, bebtelovimab appears to be of similar effectiveness as sotrovimab.