Factor VIII replacement products have improved the care of patients with hemophilia A, but the short half-life of these products affects the patients' quality of life. The half-life of recombinant factor VIII ranges from 15 to 19 hours because of the von Willebrand factor chaperone effect. BIVV001 (rFVIIIFc-VWF-XTEN) is a novel fusion protein designed to overcome this half-life ceiling and maintain high sustained factor VIII activity levels. Data are lacking on the safety and pharmacokinetics of single-dose BIVV001. ⋯ In a small, early-phase study involving men with severe hemophilia A, a single intravenous injection of BIVV001 resulted in high sustained factor VIII activity levels, with a half-life that was up to four times the half-life associated with recombinant factor VIII, an increase that could signal a new class of factor VIII replacement therapy with a weekly treatment interval. No safety concerns were reported during the 28-day period after administration. (Funded by Sanofi and Sobi; ClinicalTrials.gov number, NCT03205163.).
This massively-multicenter (235 hospitals, 24 countries; mainly Europe & N. America) cohort study investigated post-operative morbidity and mortality in those with confirmed SARS-CoV-2 infection.
Why is this significant?
Early data suggested that COVID-19 patients who underwent even minor elective surgery suffered worse post-operative outcomes, particularly higher mortality.
This large cohort study confirms these concerns and will assist decision making around the timing of surgery for COVID-19 patients and the process for re-commencing elective surgery in communities hardest hit by the pandemic.
What did they do?
Over a 3 month period in early 2020 the researchers analysed 1,128 patients who underwent emergency (74%) or elective (25%) surgery across 24 countries. Patients diagnosed with COVID seven days pre-op or 30 days post-op were included, although the majority of patients (74%) had SARS-CoV-2 infection diagnosed post-operatively.
And they found?
30-day mortality was extremely high (24%).
Pulmonary complications (pneumonia, ARDS or unexpected post-op ventilation) were very common (51%) and were associated with an even higher mortality (38%; and 83% of all deaths).
Mortality was unsurprisingly associated with older age ≥ 70 years, male sex, ASA ≥ 3, emergency surgery, major surgery, and malignancy.
Other interesting observations...
- Nonetheless 'lower-risk' groups still suffered significant 30-day mortality rates, eg. 30-49 year olds (6%), women (18%), ASA 1-2 (12%), no-comorbidities (7%).
- Being asymptomatic at admission did not have a significant protective effect (22% vs 27% mortality).
- Dyspnoea and/or sputum on admission were the only symptoms associated with worse outcomes.
- 20% of patients suffered ARDS, with a 63% mortality rate.
- Although emergency surgery was higher risk, elective surgery still carried a 19% mortality rate. Even minor surgery resulted in a 16% mortality rate!
- Even obstetrics (2% mortality) and gynaecology (5%) demonstrated orders of magnitude-higher mortality than expected.
- There was no statistically significant difference between local, regional or general anaesthesia.
- Pulmonary embolus was only seen in 2% at 30 days and when present did not appear to impact mortality.
Why such high post-operative COVID mortality?
The authors suggest this could be due to the combination of pro-inflammatory cytokine and immunosuppressive responses to surgery, and/or mechanical ventilation associated with general anaesthesia (although the later was not significantly associated with higher mortality).
Surgery for those with known or suspected COVID-19 should be avoided or delayed until after recovery from infection, as allowed by the underlying surgical pathology. When surgery cannot be delayed less-invasive surgery is preferable, and post-operative recovery should be closely monitored.
Keep in mind
Although RT-PCR testing was the main diagnostic test, in some settings clinical criteria (6%) and/or chest CT (7%) were instead used for diagnosis. Additionally, hospital data collection during a pandemic emergency carries higher risk of error, although this should not effect the broad validity of the research conclusions.summary