ABSTRACT
BACKGROUND: We performed a nationwide population-based retrospective study to describe the epidemiology of bacterial co-infections in coronavirus disease 2019 (COVID-19)-hospitalized patients in Spain in 2020. We also analyzed the risk factors for co-infection, the etiology and the impact in the outcome. METHODS: Data were obtained from records in the Minimum Basic Data Set (MBDS) of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health and annually published with 2 years lag. COVID-19 circulated in two waves in 2020: from its introduction to 31st June and from 1st July to 31st December. The risk of developing a healthcare-associated bacterial co-infection and the risk for in-hospital and intensive care unit (ICU) mortality in co-infected patients was assessed using an adjusted logistic regression model. RESULTS: The incidence of bacterial co-infection in COVID-19 hospitalized patients was 2.3%. The main risk factors associated with bacterial co-infection were organ failure, obesity and male sex. Co-infection was associated with worse outcomes including higher in-hospital, in-ICU mortality and higher length of stay. Gram-negative bacteria caused most infections. Causative agents were similar between waves, although higher co-infections with Pseudomonas spp. were detected in the first wave and with Haemophilus influenzae and Streptococcus pneumoniae in the second. CONCLUSIONS: Co-infections are not as common as those found in other viral respiratory infections; therefore, antibiotics should be used carefully. Screening for actual co-infection to prescribe antibiotic therapy when required should be performed.
ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) is currently one of the worst pandemics ever. ABO blood groups are associated with different risk of viral infections and they could also play a role in COVID-19 disease. In vitro, studies demonstrated how anti-A and B antibodies neutralized the infectious capacity of SARSCoV- 2. Both SARS-CoV-2 and antibodies let a strong competitive inhibition of angiotensin converting enzyme 2 (ACE2). Those biological mechanisms could be associated with the lower risk of severity and mortality in blood group O patients. Aims: Prospectively perform a cytokine array in plasma samples from COVID-19 patients who were stratified based on their bloody type, in order to describe the inflammatory response and provide a further insight about the possible protective mechanisms elicited by the blood type O. Methods: Prospective and consecutive study including blood samples from 108 adult patients diagnosed with COVID-19 and admitted to the "Hospital Clínico Universitario" (Valladolid, Spain) between March 24 to April 11, 2020. Percentage distribution of ABO blood type correspond to 54.6%, 9.3%, 3.7% and 32.4% for A, B, AB and O group respectively. Patients were divided into 2 groups: i. Blood type O (n=35);ii. Blood types A/B/AB (n=73). Forty-five Cytokines, Chemokines and Growth Factors were measured in duplicate for each patient using a MAGPIX system (Luminex). Statistical analysis was performed using the R statistical package version 4.0.2. Results: In both groups, most frequent comorbidities were hypertension, diabetes and chronic obstructive pulmonary disease. According to analytical profile, blood type O displayed higher lymphocytes (p=0.057) and lower total bilirubin (p=0.009) plasma levels than the A/B/AB group. We found a lower risk (2.16 times) of mechanical ventilation or death in patients with blood type O [Log Rank: p=0.042, Hazard Ratio: 0.463, CI 95% (0.213-1.004), p=0.050]. Moreover, 15 cytokines were over-express (and 1 under-expressed) in blood type O (Image upload. Left boxplots: Group A/B/AB. Right Box-plots: Group O). Last, a multivariate model found BDNF, IL-13 and IL-27 as the best cytokines able to differentiate the immune profile based on the blood type. Discussion: In first place, blood type of the general population covered by our hospital are 42%, 9%, 4% and 47% for blood types A, B, AB and O respectively. Nevertheless, our cohort found increase blood type A (54.6%) and decrease in blood type O (32.4%). Therefore, and according our results, blood type O was not only associated to a lower risk of mortality or mechanical ventilation, but also to the need of hospital admission. In second place, a strong ACE2 downregulation - competitive inhibition of ACE2 by SARS-CoV-2 and anti-A and B antibodies - associates high Ang-II plasma levels which allows the production of inflammatory cytokines and, at the same time, a possible lower infectious capacity by SARS-CoV-2 in O blood type patients. Moreover, the existence of a higher activation status of the immune system could also let a rapid activation of the immune response in patients with the O blood type and associate a quicker viral clearance. Summary/Conclusion: Our cohort showed how blood type O associated with both lower rates of hospital admission and lower risk of intubation or death. Indeed, these patients produced higher amounts of cytokines in response to SARS-CoV-2, hence mounting an effective immune response which allowed them to control the viral infection and therefore decrease the risk of further complications.