ABSTRACT
The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and related sub-lineages. Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants at two levels: (i) we tracked over 400,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using antibody pools. (ii) we mapped the antibody response at the individual level using blood from strigently curated vaccine and convalescent cohorts. In pooled antibody samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases we observed increased antibody breadth to variants that were yet to be in circulation. Resolution of viral neutralisation at the cohort level supported equivalent coverage across prior and emerging variants with emerging isolates BQ.1.1, XBB.1 and BR.2.1 the most evasive. Further, these emerging variants were resistant to Evusheld, whilst neutralization resistance to Sotrovimab was restricted to BQ.1.1 and further supported by lack of Spike glycoprotein binding to this variant. An outgrowth advantage through better utilization of TMPRSS2 was observed across BQ lineages and not those derived from BA.2.75. We conclude at this current point in time that variants derived from BQ lineages can evade antibodies at levels equivalent to their most evasive BA.2.75 counterparts but sustain an entry phenotype that would promote an additional outgrowth advantage.
ABSTRACT
BackgroundRobust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. MethodsWe conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients. FindingsWe show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression is associated with the presence of a high viral load. We further demonstrate that systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 severity. For clinical outcome prediction (e.g. respiratory failure), IFI27 expression displays a high positive (0.83) and negative (0.95) predictive value, outperforming all other known predictors of COVID-19 severity. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 swine influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients. InterpretationThese data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched the scientific literature using PubMed to identify studies that used the IFI27 biomarker to predict outcomes in COVID-19 patients. We used the search terms "IFI27", "COVID-19, "gene expression" and "outcome prediction". We did not identify any study that investigated the role of IFI27 biomarker in outcome prediction. Although ten studies were identified using the general terms of "gene expression" and "COVID-19", IFI27 was only mentioned in passing as one of the identified genes. All these studies addressed the broader question of the host response to COVID-19; none focused solely on using IFI27 to improve the risk stratification of infected patients in a pandemic. Added value of this studyHere, we present the findings of a multi-cohort study of the IFI27 biomarker in COVID-19 patients. Our findings show that the host response, as reflected by blood IFI27 gene expression, accurately predicts COVID-19 disease progression (positive and negative predictive values; 0.83 and 0.95, respectively), outperforming age, comorbidity, C-reactive protein and all other known risk factors. The strong association of IFI27 with disease severity occurs not only in SARS-CoV-2 infection, but also in other respiratory viruses with pandemic potential, such as the influenza virus. These findings suggest that host response biomarkers, such as IFI27, could help identify high-risk COVID-19 patients - those who are more likely to develop infection complications - and therefore may help improve patient triage in a pandemic. Implications of all the available evidenceThis is the first systemic study of the clinical role of IFI27 in the current COVID-19 pandemic and its possible future application in other respiratory virus pandemics. The findings not only could help improve the current management of COVID-19 patients but may also improve future pandemic preparedness.
ABSTRACT
Thirty-eight pregnant inpatients with acute pancreatitis (AP) were retrospectively reviewed from 2006 to 2012 in our hospital. The incidence of pregnancy-associated AP was 2.27‰. Most (78.95%) of the attack occurred in the third trimester. The median of APACHE II score was 6 and severe AP accounted for 31.58% (12 cases). Primary diseases were absent in most cases (57.89%). The most common clinical presentations were abdominal pain (89.47%) and vomiting (68.42%). Pleural effusion and ascites were found only in the third trimester. Elevated white blood cell count, amylase and lipase were commonly found in biochemical examinations. Eleven cases required intensive care in ICU and 21 cases received caesarean section. There were 2 maternal deaths and 12 fetal losses including 4 abortions. It is concluded that AP is a rare entity in pregnancy. The incidence of pancreatitis increases with the gestational age. However, the severity is not necessarily related with the pregnancy trimesters. The diagnosis is based on clinical presentations, laboratory tests and imaging examinations. Although the treatment strategy of a pregnant woman with pancreatitis is similar to the general non-pregnant patient with AP, a multidisciplinary team consisting of gastroenterologist, gastrointestinal surgeon, radiologist, obstetrician, and ICU doctor should be set up.
ABSTRACT
Thirty-eight pregnant inpatients with acute pancreatitis (AP) were retrospectively reviewed from 2006 to 2012 in our hospital. The incidence of pregnancy-associated AP was 2.27‰. Most (78.95%) of the attack occurred in the third trimester. The median of APACHE II score was 6 and severe AP accounted for 31.58% (12 cases). Primary diseases were absent in most cases (57.89%). The most common clinical presentations were abdominal pain (89.47%) and vomiting (68.42%). Pleural effusion and ascites were found only in the third trimester. Elevated white blood cell count, amylase and lipase were commonly found in biochemical examinations. Eleven cases required intensive care in ICU and 21 cases received caesarean section. There were 2 maternal deaths and 12 fetal losses including 4 abortions. It is concluded that AP is a rare entity in pregnancy. The incidence of pancreatitis increases with the gestational age. However, the severity is not necessarily related with the pregnancy trimesters. The diagnosis is based on clinical presentations, laboratory tests and imaging examinations. Although the treatment strategy of a pregnant woman with pancreatitis is similar to the general non-pregnant patient with AP, a multidisciplinary team consisting of gastroenterologist, gastrointestinal surgeon, radiologist, obstetrician, and ICU doctor should be set up.
