ABSTRACT
A large variation in the severity of disease symptoms is one of the key open questions in COVID-19 pandemics. The fact that only a small subset of people infected with SARS-CoV-2 develop severe disease suggests that there have to be some predisposing factors, but biomarkers that reliably predict disease severity have not been found so far. Since overactivation of the immune system is implicated in a severe form of COVID-19 and the IgG glycosylation is known to be involved in the regulation of different immune processes, we evaluated the association of inter-individual variation in IgG N-glycome composition with the severity of COVID-19. The analysis of 166 severe and 167 mild cases from hospitals in Spain, Italy and Portugal revealed statistically significant differences in the composition of the IgG N-glycome. The most notable difference was the decrease in bisecting N-acetylglucosamine (GlcNAc) in severe patients from all three cohorts. IgG galactosylation was also lower in severe cases in all cohorts, but the difference in galactosylation was not statistically significant after correction for multiple testing. To our knowledge, this is the first study exploring IgG N-glycome variability in COVID-19 severity.
ABSTRACT
BackgroundMost respiratory viruses show pronounced seasonality, but for SARS-CoV-2 this still needs to be documented. MethodsWe examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. FindingsMeta-analysis of the mortality risk in eight European hospitals estimated odds ratios per one day increase in the admission date to be 0.981 (0.973-0.988, p<0.001) and per increase in ambient temperature of one degree Celsius to be 0.854 (0.773-0.944, p=0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to Intensive Care Unit and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. InterpretationSeverity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation. Mucosal barrier and mucociliary clearance can significantly decrease viral load and disease progression, and their inactivation by low relative humidity of indoor air might significantly contribute to severity of the disease.
ABSTRACT
OBJECTIVE: The sex of the patients has been shown to affect postoperative pain and morphine consumption; still a clear understanding able to explain the reasons behind this difference struggles to emerge. Our research aimed to investigate one specific aspect of the variability in morphine consumption between sexes. Previous studies have shown that circadian rhythm can influence opioid consumption. Furthermore, circadian rhythm is different between female and male. Our analysis investigated the presence of differences in daily rhythmicity of morphine consumption between males and females. DESIGN: This is a secondary analysis of data collected during 2 years long multicenter clinical trial (NCT01233752). SETTINGS: Clinical data were collected in two Italian hospitals: IRCCS Foundation Policlinico S. Matteo (Pavia) and San Gerardo Hospital (Monza). PATIENTS: The authors recorded data about morphine consumption in 157 patients who underwent major abdominal surgery, who received morphine intravenous patient-controlled analgesia (IV-PCA) as postoperative analgesia. INTERVENTIONS: The authors analyzed the daily periodicity of effective boluses delivered by morphine IV-PCA with Poisson multilevel models, adjusted by the time of start for each pump. An effective bolus was defined as a correctly delivered bolus of 1 mg of morphine. The authors also evaluated the interactions among the time of the day and sex, age (≥55 y), and body mass index (BMI;≥30 kg/m2). MAIN OUTCOME MEASURE(S): Differences in sex of morphine consumption rhythms over the 24 hours of the day. RESULTS: Morphine consumption showed a statistically significant daily periodicity (p < 0.001) in our study population. Consumption was higher around 2 AM (rate 0.4 mg/min·patient) and lower around 12 PM (rate 0.05 mg/min·patient). Global consumption was not associated with the pump start time, age, or sex. The daily periodicity of morphine consumption was different between males and females (p = 0.004), with males consuming more morphine during the night. CONCLUSIONS: Our analysis confirmed the presence of daily rhythm for morphine consumption in patients treated with IV-PCA morphine after major abdominal surgery. A difference in the daily periodicity was observed between sexes. No difference emerged in daily periodicity for the categories of age and BMI.