Norovirus Robilotti, Elizabeth; Deresinski, Stan; Pinsky, Benjamin A
Clinical microbiology reviews
28, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Norovirus, an RNA virus of the family Caliciviridae, is a human enteric pathogen that causes substantial morbidity across both health care and community settings. Several factors enhance the ...transmissibility of norovirus, including the small inoculum required to produce infection (<100 viral particles), prolonged viral shedding, and its ability to survive in the environment. In this review, we describe the basic virology and immunology of noroviruses, the clinical disease resulting from infection and its diagnosis and management, as well as host and pathogen factors that complicate vaccine development. Additionally, we discuss overall epidemiology, infection control strategies, and global reporting efforts aimed at controlling this worldwide cause of acute gastroenteritis. Prompt implementation of infection control measures remains the mainstay of norovirus outbreak management.
The Alpha (B.1.1.7) and Omicron (B.1.1.529, BA.1, BA.4 and BA.5) variants of concern (VOC) share several mutations in their spike gene, including mutations resulting in the deletion of two amino ...acids at position 69 and 70 (del 69-70) in the Spike protein. Del 69-70 causes failure to detect the S gene target on a widely used, commercial test, the TaqPath SARS-CoV-2 RT-PCR (Thermo Fisher). The S gene target failure (SGTF) signature has been used to preliminarily infer the presence of Alpha and Omicron VOC. We evaluated the accuracy of the SGTF signature in identifying these two variants through analysis of all positive SARS-CoV-2 samples tested on the TaqPath RT-PCR and sequenced by next generation sequencing between December 2020 to July 2022. 2324 samples were successfully sequenced including 914 SGTF positive samples. The sensitivity and specificity of the SGTF signature was 99.6% (95% CI 96.1-99.9%) and 98.6% (95% CI 99.2-99.8%) for the Alpha variant and 99.6% (95% CI 98.9-99.9%) and 99.8% (95% CI 99.4-99.9%) for the Omicron variant. At the peak of their corresponding wave, the positive predictive value of the SGTF was 98% for Alpha and 100% for Omicron. The accuracy of the SGTF signature was high, making this genomic signature a rapid and accurate proxy for identification of these variants in real-world laboratory settings.
We used a self-reporting system to compare symptom frequency of hospital personnel with coronavirus disease 2019 before and after the emergence of the Omicron variant. Omicron was more likely to ...result in asymptomatic carriage (7% vs 12%;
= .009), and fewer symptoms were observed in those with booster vaccination.
Abstract
Background
There is limited information on the risk of hospital-acquired coronavirus disease 2019 (COVID-19) among high-risk hospitalized patients after exposure to an infected patient or ...healthcare worker (HCW) in a nonoutbreak setting.
Methods
This study was conducted at a tertiary care cancer center in New York City from 10 March 2020 until 28 February 2021. In early April 2020, the study institution implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing at admission and retesting every 3 days through the hospital stay. Contact tracing records were reviewed for all exposures to SARS-CoV-2 positive patients and HCWs.
Results
From 10 March 2020 to 28 February 2021, 11 348 unique patients who were SARS-CoV-2 polymerase chain reaction (PCR) negative at the time of admission underwent 31 662 postadmission tests during their hospitalization, and 112 tested positive (0.98%). Among these, 49 patients housed in semiprivate rooms during admission resulted in 74 close contacts and 14 secondary infections within 14 days, for an overall attack rate of 18.9%. Among those exposed to a roommate undergoing an aerosol-generating procedure (AGP), the attack rate was 35.7%. Whole genome sequencing (WGS) corroborated transmission in 6/8 evaluated pairs. In addition, three transmission events occurred in 214 patients with significant exposure to 105 COVID-19 positive healthcare workers (1.4%).
Conclusions
The overall risk of hospital-acquired COVID-19 is low for hospitalized cancer patients, even during periods of high community prevalence. However, shared occupancy with an unrecognized case is associated with a high secondary attack rate in exposed roommates.
There was low risk of hospital-acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients after direct contact with infected patients or healthcare workers (HCW). There was greater transmission risk during shared room occupancy with exposure to aerosol-generating procedures. Routine testing is not necessary when community rates are low.
Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality ...and severe illness.
In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing.
Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 21%) and prostate (152 16%). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality.
Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.
American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.
To describe effectiveness of mRNA vaccines by comparing 2-dose (2D) and 3-dose (3D) healthcare worker (HCW) recipients in the setting of Omicron variant dominance. Performance of 2D and 3D vaccine ...series against SARS-CoV-2 variants and the clinical outcomes of HCWs may inform return-to-work guidance.
In a retrospective study from December 15, 2020 to January 15, 2022, SARS-CoV-2 infections among HCWs at a large tertiary cancer centre in New York City were examined to estimate infection rates (aggregated positive tests / person-days) and 95% CIs over the Omicron period in 3D and 2D mRNA vaccinated HCWs and were compared using rate ratios. We described the clinical features of post-vaccine infections and impact of prior (pre-Omicron) COVID infection on vaccine effectiveness.
Among the 20857 HCWs in our cohort, 20,660 completed the 2D series with an mRNA vaccine during our study period and 12461 had received a third dose by January 15, 2022. The infection rate ratio for 3D versus 2D vaccinated HCWs was 0.667 (95% CI 0.623, 0.713) for an estimated 3D vaccine effectiveness of 33.3% compared to two doses only during the Omicron dominant period from December 15, 2021 to January 15, 2022. Breakthrough Omicron infections after 3D + 14 days occurred in 1,315 HCWs. Omicron infections were mild, with 16% of 3D and 11% 2D HCWs being asymptomatic.
Study demonstrates improved vaccine-derived protection against COVID-19 infection in 3D versus 2D mRNA vaccinees during the Omicron surge. The advantage of 3D vaccination was maintained irrespective of prior COVID-19 infection status.
As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased ...individuals
. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer
, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19
. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.
Access to rapid and accurate detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is essential for controlling the current global pandemic of coronavirus disease 2019. In ...this study, the use of oral rinses (ORs) and posterior oropharyngeal saliva as an alternative to swab collection methods from symptomatic and asymptomatic health care workers for the detection of SARS-CoV-2 RNA by RT-PCR was evaluated. For saliva samples, the overall agreement with oropharyngeal swabs was 93% (Ƙ = 0.84), with a sensitivity of 96.7% (95% CI, 83.3%–99.8%). The agreement between saliva and nasopharyngeal swabs was 97.7% (Ƙ = 0.93), with a sensitivity of 94.1% (95% CI, 73.0%–99.7%). ORs were compared with nasopharyngeal swabs only, with an overall agreement of 85.7% (Ƙ = 0.65), and a sensitivity of 63% (95% CI, 46.6%–77.8%). The agreement between a laboratory-developed test based on the CDC RT-PCR and two commercial assays, the Xpert Xpress SARS-CoV-2 and the Cobas SARS-CoV-2, was also evaluated. The overall agreement was >90%. Finally, SARS-CoV-2 RNA in saliva samples was shown to be stable, with no changes in viral loads over 24 hours at both room temperature and 4°C. Although the dilution of SARS-CoV-2 in ORs precluded its acceptability as a sample type, posterior oropharyngeal saliva was an acceptable alternative sample type for SARS-CoV-2 RNA detection.
AZD7442 (tixagevimab-cilgavimab) is a combination of two human monoclonal antibodies for pre-exposure prophylaxis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among ...high-risk patients who do not mount a reliable vaccine response. Foremost among these are hematologic malignancy patients with limited clinical trial or realworld experience to assess the effectiveness of this combination treatment since the emergence of Omicron and its subvariants. We performed a retrospective study of 892 high-risk hematologic malignancy patients who received AZD7442 at Memorial Sloan Kettering Cancer Center in New York City from January 1, 2022 to July 31, 2022. We evaluated demographic, clinical, and laboratory characteristics and performed regression analyses to evaluate risk factors for breakthrough infection. We also evaluated the impact of updated AZD7442 dosing regimens on the risk of breakthrough infection. Among 892 patients, 98 (10.9%) had a breakthrough infection during the study period. A majority received early outpatient treatment (82%) and eventually eight (8.2%) required hospitalization for management of Coronavirus Disease 2019 (COVID-19), with a single instance of severe COVID-19 and death. Patients who received a repeat dose or a higher firsttime dose of AZD7442 had a lower incidence of breakthrough infection. Univariate analyses did not reveal any significant predictors of breakthrough infection. While AZD7442 is effective at reducing SARS-CoV-2 breakthrough infection in patients with hematologic malignancies, no risk factors reliably predicted risk of infection. Patients who received updated dosing regimens as per Food and Drug Administration guidelines had better protection against breakthrough infection.
Abstract
Background
Sotrovimab is an anti-spike neutralization monoclonal antibody developed to reduce the risk of coronavirus disease 2019 (COVID-19) progression and advancement to hospitalization ...in high-risk patients. Currently, there is limited research describing the association of sotrovimab treatment in patients with hematologic malignancy and the predictive factors of hospitalization.
Methods
We performed an observational study of 156 consecutive cancer patients who received sotrovimab at Memorial Sloan Kettering Cancer Center in New York City during the BA.1 Omicron surge. We evaluated the demographic, clinical, and laboratory characteristics of the patients who had subsequent COVID-19–related hospitalization(s) compared to those who did not.
Results
Among the 156 study patients, 17 (11%) were hospitalized, of whom 4 were readmitted for COVID-19–related complications; 3 deaths were attributed to COVID-19. Results from multivariable logistic regression show that significant factors associated with hospitalization include patients on anti-CD20 therapy (adjusted odds ratio aOR, 5.59 95% confidence interval {CI}, 1.73–18.12; P = .004) and with relapse/refractory disease (aOR, 5.69 95% CI, 1.69–19.16; P = .005). Additionally, whole genome sequencing of severe acute respiratory syndrome coronavirus 2 detected high occurrences of mutations in the spike gene associated with treatment-related resistance longitudinal samples from 11 patients treated with sotrovimab.
Conclusions
While sotrovimab is effective at reducing COVID-19 hospitalization and disease severity in patients with hematologic malignancy when administered early, patients who received anti-CD20 antibodies showed substantial morbidity. Due to the high potential for resistance mutation to sotrovimab and increased morbidity in patients on anti-CD20 therapy, combination treatment should be explored to determine whether it provides added benefits compared to monotherapy.
Treatment with anti-CD20 therapy within the past year and relapse/refractory disease were associated with significantly higher odds of COVID-19–related hospitalization. Furthermore, a high occurrence of sotrovimab-related mutations was detected in the longitudinal evaluation of respiratory samples of hospitalized patients.
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