Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Humoral immunity to memory antigens and pathogens is maintained in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) have an increased risk of infection and poorer responses to vaccination. This suggests that CKD patients have an impaired responsiveness to all antigens, even those first encountered before CKD onset. To examine this we evaluated antibody responses against two childhood vaccine antigens, tetanus (TT) and diphtheria toxoids (DT) and two common pathogens, cytomegalovirus (CMV) and Salmonella enterica serovar Enteritidis (SEn) in two independent cohorts consisting of age-matched individuals with and without CKD. Sera were evaluated for antigen-specific IgG titres and the functionality of antibody to SEn was assessed in a serum bactericidal assay. Surprisingly, patients with CKD and control subjects had comparable levels of IgG against TT and DT, suggesting preserved humoral memory responses to antigens encountered early in life. Lipopolysaccharide-specific IgG titres and serum bactericidal activity in patients with CKD were also not inferior to controls. CMV-specific IgG titres in seropositive CKD patients were similar or even increased compared to controls. Therefore, whilst responses to new vaccines in CKD are typically lower than expected, antibody responses to antigens commonly encountered prior to CKD onset are not. The immunodeficiency of CKD is likely characterised by failure to respond to new antigenic challenges and efforts to improve patient outcomes should be focussed here

Anti-TT and anti-DT IgG titres in cohort 2 patients with CKD and controls with known vaccination history.

<p>Antigen-specific IgG titres (μg/ml) in cohort 2 CKD patients and age-matched controls (n = 22 and 19 respectively) are shown with medians for individuals vaccinated with TT/DT booster in preceding 10 years (blue) and those who were not (orange). The median for anti-DT IgG in controls not boosted within preceding 10 years is 0.01. A–anti-TT IgG; B–anti-DT IgG. Two-tailed Mann-Whitney p values are shown.</p

Anti-TT and anti-DT IgG titres in cohort 1 patients with CKD and controls.

<p>Antigen-specific IgG titres (μg/ml) in cohort 1 CKD patients and age-matched controls (n = 43 and 39 respectively) are shown with medians and interquartile range. A–anti-TT IgG; B–anti-DT IgG. Two-tailed Mann-Whitney p values shown.</p

Summary of demographic, clinical and laboratory data for cohort 1 patients with CKD and controls.

<p>Summary of demographic, clinical and laboratory data for cohort 1 patients with CKD and controls.</p

CMV-specific IgG titres in seropositive patients with CKD and controls.

<p>Serum CMV-specific IgG titres are shown only for seropositive patients with CKD and controls (ELISA titre greater than 10 arbitrary units, log₁₀ = 1) A: cohort 1 (n = 29 patients with CKD and 22 controls). B: cohort 2 (n = 21 patients with CKD and 13 controls). Error bars represent the median and interquartile range. Mann-Whitney 2-tailed p values shown.</p

Summary of demographic, clinical and laboratory data for cohort 2 patients with CKD and controls.

<p>Summary of demographic, clinical and laboratory data for cohort 2 patients with CKD and controls.</p

Serum-dependent killing of SEn in patients with CKD and controls.

<p>Killing curves of SEn strain D24954 by sera from A—a sub-group of cohort 1 with highest anti-LPS IgG titres: 10 patients with CKD and 9 controls; B–all patients with CKD and controls from cohort 2 (n = 25 and 20 respectively). Negative values correspond to a reduction in SEn compared with starting concentration. Antibody-depleted young healthy control serum (used as standard) served as a negative control. Error bars represent the mean +/- standard error of the mean.</p