Are co-infections important in the outcomes of patients with COVID-19? A systematic review of the emerging literature

Abstract

The current COVID-19 pandemic is the most significant infectious health problem of the last 80 years and it is currently having considerable adverse effects upon individuals, societies and economies, worldwide, due to its high morbidity and mortality, losses in productivity and rapid human to human transmission that has demanded social exclusiveness to contain the problem. A growing body of evidence has shown that coinfections are frequently detected among the respiratory isolates of patients with COVID-19 and in response to this literature, this systematic review sought to explore the extent, types and influence of co-infection upon clinical outcomes in patients with SARS-COV-2. The electronic databases of MEDLINE, EMBASE and CINAHL were searched in June 2020 and articles were limited to publication since December 2019 (emergence of SARS-COV-2) and English language. Studies were selected using a process of title and abstract screening and full-text review and eligible studies were appraised using the tools provided by the Joanna Briggs Institute. The outcomes were analysed using a narrative approach to permit sufficient description of the data pertinent to the research question. A total of 20 studies were deemed eligible for inclusion, which were of case report (n=7), case series (n=3) and cohort design (n=10). Using the Joanna Briggs Institute frameworks for these designs, the risk of bias tended to be high across most studies given the detection of >=2 systematic biases, which were largely related to the selection and characteristics of subjects. In regard to the outcomes of interest, this review found that co-infections are a frequent problem among patients hospitalised within COVID-19 where the rate was found to vary between 2.9% and 18.3%, equating to a mean frequency of 6.7%. The types of co-infective pathogens varied markedly, although the majority of isolated microorganisms of patients with COVID-19 were either other non-SARS-COV-2 viruses or bacteria with affinity or virulence to infect the upper and lower respiratory tract. The commonest bacteria, viruses and fungi isolated from patients with COVID-19 co-infections were: Mycoplasma pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, Klebsiella pneumoniae, influenza virus A, respiratory syncytial virus, rhinovirus, enterovirus, non-SARS-COV-2 coronaviruses and Candida species. The presence of co-infection was found to exacerbate the clinical course and outcomes of COVID-19 in most cases where co-infection was associated with more severe host inflammatory responses and in turn, this correlated with reports of pneumonia, acute respiratory distress syndrome, respiratory failure, sepsis, acute renal 4 failure, acute cardiac dysfunction, poor weaning from ventilation and ventilator dependence, protracted lengths of hospital and/or intensive care unit stay and a more rapid deterioration and time to death. The case fatality among patients with COVID-19 co-infection was crudely estimated to be 10%, although few studies were able to report upon the comparative mortality rate between co-infected and non-co-infected cases. Overall, the findings of this review have some implications for clinical practice, guidelines and policy, which include greater diligence and proactivity in protecting immunocompromised patients from co-infection, adherence to infection prevention and control guidelines, proactivity in testing for co-infective pathogens, revisions to guidelines that include greater acknowledge and recommendations for the diagnosis and management of co-infections and additional support at the policy level to support greater laboratory testing of co-infective pathogens. Future research should focus upon developing a large comparative study to explore the impact of co-infection upon COVID-19 outcomes, in order to validate the