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

Taxonomy and ancestral genomic features in <i>S. parasitica</i>.

<p><i>(A)</i> Animal pathogenic and plant pathogenic oomycetes reside in different taxonomic units. <i>(B)</i> Comparison of intron number in phytopathogenic oomycetes (the average count from the total genes of <i>P. infestans</i>, <i>P. ramorum</i>, <i>P. sojae</i>, <i>Py. ultimum</i> and <i>H. arabidopsidis</i>) and <i>S. parasitica</i> among all genes. <i>(C)</i> Significant difference in intron number in 4008 orthologous genes shared by <i>S. parasitica</i> and <i>Phytophthora</i> species (average intron count of <i>P. infestans</i>, <i>P. sojae</i> and <i>P. ramorum</i>). (Wilcoxon test, p<0.001). <i>(D)</i> Large number of chitinase genes belonging to CAZy family GH-18 in <i>S. parasitica</i> (red) compared to other oomycetes (black; Ps = <i>P. sojae</i>, Pr = <i>P. ramorum</i>, PITG = <i>P. infestans</i>, Hp = <i>H. arabidopsidis</i>, Pyu = <i>Py. ultimum</i>, ALNC = <i>A. laibachii</i>). The phylogenetic tree was constructed with chitinase genes from oomycetes using Maximum likelihood method.</p

Molecular genetic events associated with the evolution of animal and plant pathogenesis in oomycetes.

<p>The lineages of animal pathogens are colored red and the lineages of plant pathogens are colored green. The basal lineage is colored brown. S and N pathways refer to sulfite and nitrite assimilation, respectively.</p

Specialized proteins in the secretome of <i>S. parasitica</i>.

<p><i>(A)</i> Distributions of major classes of specialized secreted proteins compared between animal and plant pathogenic oomycetes. <i>P. infestans</i> represents <i>Phytophthora</i> species. <i>(B) S. parasitica</i> secreted proteins that carry various lectin domain fusions are schematically drawn. Domains or domain architectures unique to <i>S. parasitica</i> are marked with an asterisk. Proteins containing single domains are also listed. <i>(C)</i> Phylogenetic relationship of lectins. The <i>S. parasitica</i> disintegrin gene (SPRG_01285 groups with bacterial homologs; gal_lectin gene (SPRG_05731)) groups with animal species. All other paralogous <i>S. parasitica</i> disintegrin and gal_lectin genes group closely with these two representatives, respectively, and are not shown.</p

Genome statistics and intron features of oomycetes.

a<p>Total contig length adjusted for the regions of haplotype assemblies.</p>b<p>Genome statistics derived from publication of these genomes.</p>c<p>Measured by repeatMasker with de novo RepeatScout.</p>d<p>The repeat content in the assembled sequence is listed in the brackets.</p

Metabolic adaptations to animal pathogenesis.

<p><i>(A)</i> Independent degeneration of nitrite and sulfite metabolic pathways in animal pathogens and obligate biotrophic plant pathogens. Red cross indicates the gene encoding the enzyme is absent in the genome. <i>(B)</i> Lineage specific expansion of amino acid transporters. Members from <i>Pythium</i> (black), <i>Hyaloperonospora</i> (green), <i>Albugo</i> (blue) and <i>S. parasitica</i> (red) are included. - The <i>S. parasitica</i>-specific clade is marked with red dots. <i>(C)</i> Secreted peptidase families in <i>S. parasitica</i> and phytopathogenic oomycetes (the average count from the total peptidase genes of <i>P. infestans</i>, <i>P. ramorum</i>, <i>P. sojae</i>, <i>Py. ultimum</i> and <i>H. peronospora</i>) . Peptidase_C1, Peptidase_S8 and Peptidase_S10 are the largest families in <i>S. parasitica</i>. <i>(D)</i> Lineage-specific expansion of peptidase_C1 family. Members from <i>P. sojae</i>, <i>P. ramorum</i> and <i>P. infestans</i> (black) and <i>S. parasitica</i> (red) are included. The <i>S. parasitica</i>-specific clade is marked with red dots.</p

Rainbow trout IgM proteolysis by <i>S. parasitica</i> secreted proteases.

<p>(<b>A</b>) 7-day old culture filtrates were capable of degrading rainbow trout IgM after an overnight incubation at 10°C. (<b>B</b>) Schematic drawing of the domains present in the protease SPRG_14567 (<b>C</b>) Expression pattern of SPRG_14567 in different life stages. The RKPM of RNA-seq data is plotted, and the previously identified effector SpHTP-1 is plotted to show contrasting expression patterns. (<b>D</b>) The recombinant subtilisin-like protease SPRG_14567 was partially purified through tandem ion exchange (SO₃⁻) and nickel affinity columns (Fractions 1 to 4) following detection in a Western blot using anti-(His)₅ HRP antibody. (<b>E</b>) Fractions 2, 3 and soluble proteins from untransformed <i>E. coli</i> were tested for IgM-degrading activity with only the fraction containing the recombinant SPRG_14567 exhibiting proteolysis.</p

Predicted horizontally transferred genes that may be associated with pathogenesis in <i>Saprolegnia parasitica</i>.

a<p>Subcellular localization is predicted by the N-terminal signal peptide, mitochondrial targeting motif and transmembrane domains.</p>b<p>The time of horizontal gene transfer is estimated by the presence in other oomycetes and coding potential of a given gene. ‘a recently acquired gene’ refers to a gene occurring only in <i>Saprolegnia</i> and having an uncharacteristic coding potential.</p

Differentially expressed genes detected by RNA-Seq.

<p><i>(A)</i> Percentage of differentially expressed genes in pair-wise comparisons of tissue types. Genes with 4 fold RPKM (reads per kilobase per million) differences were considered to be differentially expressed (negative binomial exact test p<0.001, p value adjusted with Benjamini & Hochberg correction, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003272#pgen.1003272.s024" target="_blank">Table S12</a>) <i>(B)</i> Gene families showing differential expression between vegetative tissue (mycelia and sporulating mycelia) and pre-infection tissues (cysts and germinating cysts). CBEL:fungal Cellulose Binding Domain Like protein, EGF:(Epidermal Growth Factor, gal_lectin: Galactose binding Lectin domain, HST: Heat shock factors, PLAC8: Placenta-specific gene 8 protein, SDF: Sodium Dicarboxylate symporter Family (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003272#pgen.1003272.s025" target="_blank">Table S13</a>). <i>(C)</i> Growth phase specific expression of peptidases and protease inhibitors (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003272#pgen.1003272.s026" target="_blank">Table S14</a>). <i>(D)</i> Relative abundance of <i>S. parasitica</i> and fish transcripts during interaction. <i>(E)</i>. <i>S. parasitica</i> transcript distribution in pre-infection versus vegetative tissue. logFC = log₂(pre-infection/vegetative/pre-infection); logConc = the log2 of average reads counts per million of each gene in the two tissue types,). Red dots indicate significant differences (p<0.001; negative binomial test).</p