The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or ...vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT
) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3-5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT
titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed.
Diaphragm weakness is highly prevalent in critically ill patients. It may exist prior to ICU admission and may precipitate the need for mechanical ventilation but it also frequently develops during ...the ICU stay. Several risk factors for diaphragm weakness have been identified; among them sepsis and mechanical ventilation play central roles. We employ the term critical illness-associated diaphragm weakness to refer to the collective effects of all mechanisms of diaphragm injury and weakness occurring in critically ill patients. Critical illness-associated diaphragm weakness is consistently associated with poor outcomes including increased ICU mortality, difficult weaning, and prolonged duration of mechanical ventilation. Bedside techniques for assessing the respiratory muscles promise to improve detection of diaphragm weakness and enable preventive or curative strategies. Inspiratory muscle training and pharmacological interventions may improve respiratory muscle function but data on clinical outcomes remain limited.
A new phenotypic test, called the Carbapenem Inactivation Method (CIM), was developed to detect carbapenemase activity in Gram-negative rods within eight hours. This method showed high concordance ...with results obtained by PCR to detect genes coding for the carbapenemases KPC, NDM, OXA-48, VIM, IMP and OXA-23. It allows reliable detection of carbapenemase activity encoded by various genes in species of Enterobacteriaceae (e.g., Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae), but also in non-fermenters Pseudomonas aeruginosa and Acinetobacter baumannii. The CIM was shown to be a cost-effective and highly robust phenotypic screening method that can reliably detect carbapenemase activity.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus with high nucleotide identity to SARS-CoV and to SARS-related coronaviruses that have been detected in horseshoe ...bats, has spread across the world and had a global effect on healthcare systems and economies
. A suitable small animal model is needed to support the development of vaccines and therapies. Here we report the pathogenesis and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters (Mesocricetus auratus). Immunohistochemistry assay demonstrated the presence of viral antigens in nasal mucosa, bronchial epithelial cells and areas of lung consolidation on days 2 and 5 after inoculation with SARS-CoV-2, followed by rapid viral clearance and pneumocyte hyperplasia at 7 days after inoculation. We also found viral antigens in epithelial cells of the duodenum, and detected viral RNA in faeces. Notably, SARS-CoV-2 was transmitted efficiently from inoculated hamsters to naive hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was not as efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally infected hamsters showed apparent weight loss on days 6-7 post-inoculation or post-contact; all hamsters returned to their original weight within 14 days and developed neutralizing antibodies. Our results suggest that features associated with SARS-CoV-2 infection in golden hamsters resemble those found in humans with mild SARS-CoV-2 infections.
The SARS-CoV-2 pandemic poses the greatest global public health challenge in a century. Neutralizing antibody is a correlate of protection and data on kinetics of virus neutralizing antibody ...responses are needed. We tested 293 sera from an observational cohort of 195 reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections collected from 0 to 209 days after onset of symptoms. Of 115 sera collected ≥61 days after onset of illness tested using plaque reduction neutralization (PRNT) assays, 99.1% remained seropositive for both 90% (PRNT
) and 50% (PRNT
) neutralization endpoints. We estimate that it takes at least 372, 416 and 133 days for PRNT
titres to drop to the detection limit of a titre of 1:10 for severe, mild and asymptomatic patients, respectively. At day 90 after onset of symptoms (or initial RT-PCR detection in asymptomatic infections), it took 69, 87 and 31 days for PRNT
antibody titres to decrease by half (T
) in severe, mild and asymptomatic infections, respectively. Patients with severe disease had higher peak PRNT
and PRNT
antibody titres than patients with mild or asymptomatic infections. Age did not appear to compromise antibody responses, even after accounting for severity. We conclude that SARS-CoV-2 infection elicits robust neutralizing antibody titres in most individuals.
Abstract
Background
A novel coronavirus of zoonotic origin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus ...and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are urgently needed for early identification of infected patients.
Methods
We developed two 1-step quantitative real-time reverse-transcription PCR assays to detect two different regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, respiratory specimens from two 2019-nCoV-infected patients were tested.
Results
Using RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x10−4-2000 TCID50/reaction). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control samples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests.
Conclusions
The established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at ...https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
OBJECTIVES
To determine predictors of new activities of daily living (ADLs) disability and worsened mobility disability and secondarily increased daily care hours received, in previously independent ...hip fracture patients.
DESIGN
Retrospective cohort study.
SETTING
Academic hospital with ambulatory follow‐up.
PARTICIPANTS
Community‐dwelling adults 65 years or older independent in ADLs undergoing hip fracture surgery in 2015 (n = 184).
MEASUREMENTS
Baseline, 3‐ and 6‐month ADLs, mobility, and daily care hours received were ascertained by telephone survey and chart review. Comorbidities, medications, and characteristics of hospitalization were extracted from patient charts. Models for each outcome used logistic regression with a backward elimination strategy, adjusting a priori for age, sex, and race.
RESULTS
Predictors of new ADL disability at 3 months were dementia (odds ratio OR = 11.81; P = .001) and in‐hospital delirium (OR = 4.20; P = .002), and at 6 months were age (OR = 1.04; P = .014), dementia (OR = 9.91; P = .001), in‐hospital delirium (OR = 3.00; P = .031) and preadmission opiates (OR = 7.72; P = .003). Predictors of worsened mobility at 3 months were in‐hospital delirium (OR = 4.48; P = .001) and number of medications (OR = 1.13; P = .003), and at 6 months were age (OR = 1.06; P = .001), preadmission opiates (OR = 7.23; P = .005), in‐hospital delirium (OR = 3.10; P = .019), and number of medications (OR = 1.13; P = .013). Predictors of increased daily care hours received at 3 and 6 months were age (3 months: OR = 1.07; P = .014; 6 months: OR = 1.06; P = .017) and number of medications (3 months: OR = 1.13; P = .004; 6 months: OR = 1.22; P = .013). The proportion of patients with ADL disability and care hours received did not change from 3 to 6 months, yet there were significant improvements in mobility.
CONCLUSION
Age, dementia, in‐hospital delirium, number of medications, and preadmission opiate use were predictors of poor outcomes in independent older adults following hip fracture. Further investigation is needed to identify factors associated with improved mobility measures from 3 to 6 months to ultimately optimize recovery.
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