Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020

Background: Women are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Aim: We assessed the impact of sex and gender on PASC in a Swiss population. Method: Our multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030). Conclusion: Specific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident

XMeis3 Is Necessary for Mesodermal Hox Gene Expression and Function

Hox transcription factors provide positional information during patterning of the anteroposterior axis. Hox transcription factors can co-operatively bind with PBC-class co-factors, enhancing specificity and affinity for their appropriate binding sites. The nuclear localisation of these co-factors is regulated by the Meis-class of homeodomain proteins. During development of the zebrafish hindbrain, Meis3 has previously been shown to synergise with Hoxb1 in the autoregulation of Hoxb1. In Xenopus XMeis3 posteriorises the embryo upon ectopic expression. Recently, an early temporally collinear expression sequence of Hox genes was detected in Xenopus gastrula mesoderm (see intro. P3). There is evidence that this sequence sets up the embryo's later axial Hox expression pattern by time-space translation. We investigated whether XMeis3 is involved in regulation of this early mesodermal Hox gene expression. Here, we present evidence that XMeis3 is necessary for expression of Hoxd1, Hoxb4 and Hoxc6 in mesoderm during gastrulation. In addition, we show that XMeis3 function is necessary for the progression of gastrulation. Finally, we present evidence for synergy between XMeis3 and Hoxd1 in Hoxd1 autoregulation in mesoderm during gastrulation

In Vivo Monitoring of mRNA Movement in Drosophila Body Wall Muscle Cells Reveals the Presence of Myofiber Domains

Background: In skeletal muscle each muscle cell, commonly called myofiber, is actually a large syncytium containing numerous nuclei. Experiments in fixed myofibers show that mRNAs remain localized around the nuclei in which they are produced. Methodology/Principal Findings: In this study we generated transgenic flies that allowed us to investigate the movement of mRNAs in body wall myofibers of living Drosophila embryos. We determined the dynamic properties of GFP-tagged mRNAs using in vivo confocal imaging and photobleaching techniques and found that the GFP-tagged mRNAs are not free to move throughout myofibers. The restricted movement indicated that body wall myofibers consist of three domains. The exchange of mRNAs between the domains is relatively slow, but the GFP-tagged mRNAs move rapidly within these domains. One domain is located at the centre of the cell and is surrounded by nuclei while the other two domains are located at either end of the fiber. To move between these domains mRNAs have to travel past centrally located nuclei. Conclusions/Significance: These data suggest that the domains made visible in our experiments result from prolonged interactions with as yet undefined structures close to the nuclei that prevent GFP-tagged mRNAs from rapidly moving between the domains. This could be of significant importance for the treatment of myopathies using regenerative cellbase

Recurrent laryngeal nerve monitoring during esophagectomy and mediastinal lymph node dissection

BACKGROUND: Patients who undergo surgery to the esophagus and lungs are in jeopardy of recurrent laryngeal nerve (RLN) damage during the procedure. This study was designed to investigate the feasibility of intraoperative monitoring of the RLN for single-lung ventilation esophagus and lung surgery. METHODS: Twelve consecutive patients booked for esophagus or lung surgery were included in this prospective, observational study. Six patients underwent transthoracic esophagectomy for carcinoma of the esophagogastric junction or lower esophagus, five had a lobectomy, and one underwent a pneumonectomy for lung carcinoma. Intraoperative, noninvasive RLN identification and monitoring was performed unilaterally (n = 8) or bilaterally (n = 4) using a handheld stimulator and a laryngeal surface electrode. The correct functioning of the nerve monitoring system was tested directly at the vagus nerve. Diagnosis of postoperative RLN paralysis was performed using indirect laryngoscopy. RESULTS: During the surgical procedures, we monitored a nerve signal in all 12 patients. In one patient with lower esophagus carcinoma, a nerve signal could be detected only on one side. Postoperative indirect laryngoscopy showed normal vocal cord movement in all patients. CONCLUSIONS: Intraoperative RLN identification and monitoring during single-lung ventilation surgery is technically feasible, easy, and reliable. The introduction of standardized RLN monitoring during this type of surgery may reduce the incidence of permanent RLN paralysis

A multicenter randomized clinical trial of primary anastomosis or Hartmann's procedure for perforated left colonic diverticulitis with purulent or fecal peritonitis

OBJECTIVES: To evaluate the outcome after Hartmann's procedure (HP) versus primary anastomosis (PA) with diverting ileostomy for perforated left-sided diverticulitis. BACKGROUND: The surgical management of left-sided colonic perforation with purulent or fecal peritonitis remains controversial. PA with ileostomy seems to be superior to HP; however, results in the literature are affected by a significant selection bias. No randomized clinical trial has yet compared the 2 procedures. METHODS: Sixty-two patients with acute left-sided colonic perforation (Hinchey III and IV) from 4 centers were randomized to HP (n = 30) and to PA (with diverting ileostomy, n = 32), with a planned stoma reversal operation after 3 months in both groups. Data were analyzed on an intention-to-treat basis. The primary end point was the overall complication rate. The study was discontinued following an interim analysis that found significant differences of relevant secondary end points as well as a decreasing accrual rate (NCT01233713). RESULTS: Patient demographics were equally distributed in both groups (Hinchey III: 76% vs 75% and Hinchey IV: 24% vs 25%, for HP vs PA, respectively). The overall complication rate for both resection and stoma reversal operations was comparable (80% vs 84%, P = 0.813). Although the outcome after the initial colon resection did not show any significant differences (mortality 13% vs 9% and morbidity 67% vs 75% in HP vs PA), the stoma reversal rate after PA with diverting ileostomy was higher (90% vs 57%, P = 0.005) and serious complications (Grades IIIb-IV: 0% vs 20%, P = 0.046), operating time (73 minutes vs 183 minutes, P < 0.001), hospital stay (6 days vs 9 days, P = 0.016), and lower in-hospital costs (US \$16,717 vs US \$24,014) were significantly reduced in the PA group. CONCLUSIONS: This is the first randomized clinical trial favoring PA with diverting ileostomy over HP in patients with perforated diverticulitis

Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

Background Women are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Aim We assessed the impact of sex and gender on PASC in a Swiss population. Method Our multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030). Conclusion Specific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident

Understanding the Impact of Sociocultural Gender on Post-acute Sequelae of COVID-19: a Bayesian Approach

Background Women are overrepresented amongst individuals suffering from post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Methods and Findings By using Bayesian models comprising >200 co-variates, we assessed the impact of social context in addition to biological data on PASC in a multi-centre prospective cohort study of 2927 (46% women) individuals in Switzerland. Women more often reported at least one persistent symptom than men (43.5% vs 32.0% of men, p<0.001) six (IQR 5–9) months after SARS-CoV-2 infection. Adjusted models showed that women with personality traits stereotypically attributed to women were most often affected by PASC (OR 2.50[1.25-4.98], p<0.001), in particular when they were living alone (OR 1.84[1.25-2.74]), had an increased stress level (OR 1.06[1.03-1.09]), had undergone higher education (OR 1.30[1.08-1.54]), preferred pre-pandemic physical greeting over verbal greeting (OR 1.71[1.44-2.03]), and had experienced an increased number of symptoms during index infection (OR 1.27[1.22-1.33]). Conclusion Besides gender- and sex-sensitive biological parameters, sociocultural variables play an important role in producing sex differences in PASC. Our results indicate that predictor variables of PASC can be easily identified without extensive diagnostic testing and are targets of interventions aiming at stress coping and social support. Competing Interest Statement CG has received research grants from the Novartis Foundation and speakers fees from Sanofi Genzyme, Switzerland outside of the submitted work. The University Hospital Zurich (CG, RRB, APP, MM, PAK) holds a research contract with GE Healthcare outside of the submitted work. CG and AM have received research grants from Bayer Pharmaceuticals outside of the submitted work. JCS and TS reports (full departmental disclosure) grants from Orion Pharma, Abbott Nutrition International, B. Braun Medical AG, CSEM AG, Edwards Lifesciences Services GmbH, Kenta Biotech Ltd, Maquet Critical Care AB, Omnicare Clinical Research AG, Nestle, Pierre Fabre Pharma AG, Pfizer, Bard Medica S.A., Abbott AG, Anandic Medical Systems, Pan Gas AG Healthcare, Bracco, Hamilton Medical AG, Fresenius Kabi, Getinge Group Maquet AG, Draeger AG, Teleflex Medical GmbH, Glaxo Smith Kline, Merck Sharp and Dohme AG, Eli Lilly and Company, Baxter, Astellas, Astra Zeneca, CSL Behring, Novartis, Covidien, Nycomed, and Phagenesis, outside of the submitted work. The money went into departmental funds, no personal financial gain applies. All other authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work

Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion

The host responds to virus infection by activating type I interferon (IFN) signaling leading to expression of IFN-stimulated genes (ISGs). Dysregulation of the IFN response results in inflammatory diseases and chronic infections. In this study, we demonstrate that IFN regulatory factor 2 (IRF2), an ISG and a negative regulator of IFN signaling, influences alphavirus neuroinvasion and pathogenesis. A Sindbis virus strain that in wild-type (WT) mice only causes disease when injected into the brain leads to lethal encephalitis in Irf2(−/−) mice after peripheral inoculation. Irf2(−/−) mice fail to control virus replication and recruit immune infiltrates into the brain. Reduced B cells and virus-specific IgG are observed in the Irf2(−/−) mouse brains despite the presence of peripheral neutralizing antibodies, suggesting a defect in B cell trafficking to the central nervous system (CNS). B cell–deficient μMT mice are significantly more susceptible to viral infection, yet WT B cells and serum are unable to rescue the Irf2(−/−) mice. Collectively, our data demonstrate that proper localization of B cells and local production of antibodies in the CNS are required for protection. The work advances our understanding of host mechanisms that affect viral neuroinvasion and their contribution to immunity against CNS infections