Secondary Complement Deficiency Impairs Anti-Microbial Immunity to Klebsiella pneumoniae and Staphylococcus aureus During Severe Acute COVID-19.

A high incidence of secondary Klebsiella pneumoniae and Staphylococcus aureus infection were observed in patients with severe COVID-19. The cause of this predisposition to infection is unclear. Our data demonstrate consumption of complement in acute COVID-19 patients reflected by low levels of C3, C4, and loss of haemolytic activity. Given that the elimination of Gram-negative bacteria depends in part on complement-mediated lysis, we hypothesised that secondary hypocomplementaemia is rendering the antibody-dependent classical pathway activation inactive and compromises serum bactericidal activity (SBA). 217 patients with severe COVID-19 were studied. 142 patients suffered secondary bacterial infections. Klebsiella species were the most common Gram-negative organism, found in 58 patients, while S. aureus was the dominant Gram-positive organism found in 22 patients. Hypocomplementaemia was observed in patients with acute severe COVID-19 but not in convalescent survivors three months after discharge. Sera from patients with acute COVID-19 were unable to opsonise either K. pneumoniae or S. aureus and had impaired complement-mediated killing of Klebsiella. We conclude that hyperactivation of complement during acute COVID-19 leads to secondary hypocomplementaemia and predisposes to opportunistic infections.

Critical Care Workers Have Lower Seroprevalence of SARS-CoV-2 IgG Compared with Non-patient Facing Staff in First Wave of COVID19.

INTRODUCTION: In early 2020, at first surge of the coronavirus disease 2019 (COVID-19) pandemic, many health care workers (HCW) were re-deployed to critical care environments to support intensive care teams looking after patients with severe COVID-19. There was considerable anxiety of increased risk of COVID-19 for these staff. To determine whether critical care HCW were at increased risk of hospital acquired infection, we explored the relationship between workplace, patient facing role and evidence of immune exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a quaternary hospital providing a regional critical care response. Routine viral surveillance was not available at this time. METHODS: We screened over 500 HCW (25% of the total workforce) for history of clinical symptoms of possible COVID19, assigning a symptom severity score, and quantified SARS-CoV-2 serum antibodies as evidence of immune exposure to the virus. RESULTS: Whilst 45% of the cohort reported symptoms that they consider may have represented COVID-19, 14% had evidence of immune exposure. Staffs in patient facing critical care roles were least likely to be seropositive (9%) and staff working in non-patient facing roles most likely to be seropositive (22%). Anosmia and fever were the most discriminating symptoms for seropositive status. Older males presented with more severe symptoms. Of the 12 staff screened positive by nasal swab (10 symptomatic), 3 showed no evidence of seroconversion in convalescence. CONCLUSIONS: Patient facing staff working in critical care do not appear to be at increased risk of hospital acquired infection however the risk of nosocomial infection from non-patient facing staff may be more significant than previous recognised. Most symptoms ascribed to possible COVID-19 were found to have no evidence of immune exposure however seroprevalence may underrepresent infection frequency. Older male staff were at the greatest risk of more severe symptoms.

Bacteremia in children: epidemiology, clinical diagnosis and antibiotic treatment.

The diagnosis of bacteremia in children is important and it can be clinically challenging to recognize the signs and symptoms. The reported rates of bacteremia are higher in young children but with the increasing vaccine coverage, there has been a decrease in bacteremia due to the three vaccine preventable bacteria (Streptococcus pneumoniae, Haemophilus influenzae group b and Neisseria meningitidis). Notably, there have been increases in healthcare-associated bacteremias with a rise in Staphylococcus aureus and Gram negative bacteremias. This review provides a brief overview of the clinical diagnosis of bacteremia in children, focusing on the epidemiology, clinical characteristics, risk factors, antibiotic treatment, outcomes and preventative measures to reduce the incidence of bacteremia and improve morbidity and mortality.

Delayed Diagnosis of Q Fever: Finally Diagnosed After Elective Cardiac Surgery.

Q fever is a bacterial infection caused by Coxiella burnetti. It can cause both acute and chronic illness. Chronic QF can present as a variety of clinical syndromes. A common and critical manifestation is endocarditis which can present atypically and is easily missed. This case describes a man who, after extensive investigation for splenomegaly and pancytopenia by several specialties, was finally diagnosed with Q fever endocarditis after unexpected aortic valve abnormalities found during elective cardiac surgery. Several factors contributed to diagnostic delay including aspects of clinical assessment and radiologic findings. Vigilance is essential for diagnosis and prompt initiation of effective treatment.

Campylobacter gastroenteritis associated with Sweet's syndrome.

Sweet's syndrome or acute febrile neutrophilic dermatosis has been associated with underlying infection, malignancy, inflammatory disease and certain medications. The infection agents associated with this include Streptococcus species, Yersinia species, Chlamydia species, Salmonella species and Helicobacter pylori. We report a case of Sweet's syndrome in a 73-year-old woman following a 2 week course of severe gastroenteritis caused by Campylobacter species. Histological examination of skin lesions showed marked inflammatory infiltrate throughout the dermis, composed of neutrophils and histiocytes. The patient was successfully treated with topical and systemic steroids. To date, this is the first case of Sweet's syndrome to be reported linked to Campylobacter species to our knowledge.

Five years experience of Clostridium difficile infection in children at a UK tertiary hospital: proposed criteria for diagnosis and management.

BACKGROUND: Clostridium difficile infection (CDI) is associated with significant morbidity and mortality in adults. There is increasing evidence of the pathogenic role of C. difficile in the paediatric population. We sought to ascertain the clinical presentation and severity of CDI in children at our institution and develop criteria to aid management. METHODS: Clinical data was retrospectively collected from all children (0-16 yrs) with a positive C. difficile toxin result over a 5-year period. National adult guidelines were used to assess the severity and management of CDI. RESULTS: Seventy-five patients were included with a mean age of 2.97 years. Forty-nine were hospital onset, 22 community onset and 4 healthcare-associated. The most common co-morbidity among the hospital onset infections was malignancy. Gastrointestinal conditions were most common among community onset infections. Fifty-five cases (73.3%) had received antibiotics in the preceding month, 7 (9.3%) had cow's milk intolerance and 9 (12%) had co-infection with another gut pathogen. According to national adult guidelines 57 cases (76%) were categorised as severe. Thirty cases received oral metronidazole, two patients required intensive care and one patient had a sub-total colectomy for pseudomembranous colitis. No mortality was observed. DISCUSSION: We confirm the association of paediatric CDI with co-morbidities such as haematological and solid organ malignancies, recent antibiotic use and hospitalisation. We observed an association between cows milk protein intolerance and C. difficile. The use of adult criteria overestimated severity of disease in this cohort, as most cases experienced a mild course of illness with low morbidity and no mortality. This indicates that adult scoring criteria are not useful in guiding management and we propose specific criteria for children.

Clostridium difficile in children: colonisation and disease.

Clostridium difficile is the commonest cause of hospital acquired diarrhoea in adults and is associated with significant mortality and morbidity. The clinical significance of C. difficile in children, however, is less certain. In this article we discuss colonisation and infection and describe C. difficile in childhood in terms of risk factors, epidemiology and management.