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1.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326824

ABSTRACT

The Omicron (B.1.1.529) variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 (coronavirus disease 2019) vaccines and antibody therapies4. This concern is amplified by the findings from our study. We found B.1.1.529 to be markedly resistant to neutralization by serum not only from convalescent patients, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 17 of the 19 antibodies tested were either abolished or impaired, including ones currently authorized or approved for use in patients. In addition, we also identified four new spike mutations (S371L, N440K, G446S, and Q493R) that confer greater antibody resistance to B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.

2.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326792

ABSTRACT

The devastation caused by SARS-CoV-2 has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses and thus its promise as an agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses, but also uncovered a new antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

3.
Diabetes Metab ; 47(6): 101267, 2021 11.
Article in English | MEDLINE | ID: covidwho-1330743

ABSTRACT

AIM: - Patients with diabetes have increased morbidity and mortality from COVID-19. Case reports describe patients with simultaneous COVID-19 and diabetic acidosis (DKA), however there is limited data on the prevalence, predictors and outcomes of DKA in these patients. METHODS: - Patients with COVID-19 were identified from the electronic medical record. DKA was defined by standardized criteria. Proportional hazard regression models were used to determine risk factors for, and mortality from DKA in COVID-19. RESULTS: - Of 2366 patients admitted for COVID-19, 157 (6.6%) patients developed DKA, 94% of whom had antecedent type 2 diabetes, 0.6% had antecedent type 1 diabetes, and 5.7% patients had no prior diagnosis of diabetes. Patients with DKA had increased hospital length of stay and in-patient mortality. Higher HbA1c predicted increased risk of incident DKA (HR 1.47 per 1% increase, 95% CI 1.40-1.54). Risk factors for mortality included older age (HR 1.07 per 5 years, 95% CI 1.06-1.08) and need for pressors (HR 2.33, 95% CI 1.82-2.98). Glucocorticoid use was protective in patients with and without DKA. CONCLUSION: - The combination of DKA and COVID-19 is associated with greater mortality, driven by older age and COVID-19 severity.


Subject(s)
COVID-19 , Diabetic Ketoacidosis , Aged , COVID-19/mortality , Diabetic Ketoacidosis/epidemiology , Humans
4.
Topics in Antiviral Medicine ; 29(1):69-70, 2021.
Article in English | EMBASE | ID: covidwho-1250818

ABSTRACT

Background: SARS-CoV2 can infect enterocytes, and plasma cells and lymphocytes infiltrate the GI tract. In HIV, increased intestinal permeability and the ensuing microbial translocation are thought to contribute to systemic inflammation. We hypothesize that severe COVID-19 is associated with increased intestinal permeability, leading to microbial translocation and systemic inflammation. Methods: Serum/plasma samples were obtained from participants enrolled in a longitudinal COVID-19 study. Participants had Mild (outpatient), Moderate (inpatient but not requiring Intensive Care Unit (ICU) level care or mechanical ventilation), or Severe (inpatient requiring ICU level care and mechanical ventilation or ECMO) COVID-19. Intestinal fatty acid binding protein (iFABP), lipopolysaccharide binding protein (LBP), and soluble CD14 (sCD14) were measured by ELISA. Student's t-tests were used for between group comparisons, and paired t-tests were used for within group comparisons. Results: Participants with Moderate and Severe COVID-19 presentations were older compared to the Mild group (p<0.001) (Mild: 42.2 years (range: 20-63 years), Moderate: 64.2 years (range: 33-97 years);Severe: 61.9 years (range: 32-86 years)). The Severe group had a greater proportion of men (69% vs 36%) than women and a greater proportion of black/African Americans (27% vs 6%) than whites versus the Mild group. iFABP, LBP, and sCD14 levels were significantly higher in participants with Moderate or Severe disease compared to Mild disease (Table 1), with no significant differences between Moderate and Severe groups. Among the 65 participants with samples from two timepoints (mean separation of 24.3+/-22.4 days), sCD14, iFABP, and LBP did not change significantly. Conclusion: Levels of biomarkers of enterocyte turnover (iFABP), microbial translocation (LBP), and lipopolysaccharide-induced monocyte activation (sCD14) were increased in patients with Moderate and Severe COVID-19 compared to Mild COVID-19. Whether interventions that improve gut health will attenuate the cytokine storm that precipitates Severe COVID-19 needs further study.

5.
Topics in Antiviral Medicine ; 29(1):210, 2021.
Article in English | EMBASE | ID: covidwho-1250705

ABSTRACT

Background: The long-term sequelae of coronavirus disease 2019 (COVID-19) have been increasingly recognized. Cardiac, pulmonary, and neuropsychiatric symptoms have been reported to persist up to two months after hospitalization. However, much remains to be learned about the durable long-term effects of COVID-19 for patients and the health care system. Here, we describe the persistence of COVID-19 sequelae up to six months after presentation. Methods: We examined the electronic medical records of the first 1190 patients diagnosed with SARS-CoV-2 infection by reverse transcriptase polymerase chain reaction assay and hospitalized at a quaternary-care center in New York City. All initial hospital presentations occurred between March 1 and April 8, 2020. We manually abstracted data for two follow-up periods representing three-and six-months post-hospitalization. Abstracted information included type and dates of encounters;use of tele-health;presence and persistence of symptoms;morbidity;and mortality. Descriptive statistics for categorical and continuous variables were tabulated and distributions were examined by visit;at presentation, three months and six months. Results: Patients had a median age of 60 and 61 years at three and six months, respectively. About 45% were female and 50% identified as Hispanic/Latinx. Of 1190 patients, 78% (N=928) survived their initial hospitalization. Among the 61% (n=570) of survivors who had follow-up encounters at three and six months, patients frequently reported cardiopulmonary symptoms (35.7% and 28%), dyspnea (22.1% and 15.9%), generalized symptoms (25.4 % and 26.4%) and neuropsychiatric symptoms (20.1% and 24.2%). Tele-health encounters represented 59% and 28.2% of encounters at three and six-months, respectively. Twenty-percent of patients had reduced mobility or reduced independence in the six months after hospitalization. Of survivors, 17% weredischarged to a nursing or rehabilitation facility and 10.3% remained there at three months post-hospitalization. Conclusion: The prevalence was high of at least one COVID-associated symptom six months after hospitalization. Cardiopulmonary symptoms were most common and persisted longer than previously reported. Providers, patients, and their families must be sensitized to and anticipate these potential sequelae. Further follow-up and studies of COVID-19 survivors are necessary to confirm these findings and investigate outcomes beyond six months. (Figure Presented).

6.
Journal of Bone and Mineral Research ; 35:47-48, 2020.
Article in English | Web of Science | ID: covidwho-1008519
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