The role of co-infections and secondary infections in patients with COVID-19

Abstract

Background It has been recognised for a considerable time-period, that viral respiratory infections predispose patients to bacterial infections, and that these co-infections have a worse outcome than either infection on its own. However, it is still unclear what exact roles co-infections and/or superinfections play in patients with COVID-19 infection. Main body This was an extensive review of the current literature regarding co-infections and superinfections in patients with SARS-CoV-2 infection. The definitions used were those of the Centers for Disease Control and Prevention (US), which defines coinfection as one occurring concurrently with the initial infection, while superinfections are those infections that follow on a previous infection, especially when caused by microorganisms that are resistant, or have become resistant, to the antibiotics used earlier. Some researchers have envisioned three potential scenarios of bacterial/SARS-CoV-2 co-infection; namely, secondary SARS-CoV-2 infection following bacterial infection or colonisation, combined viral/bacterial pneumonia, or secondary bacterial superinfection following SARS-CoV-2. There are a myriad of published articles ranging from letters to the editor to systematic reviews and meta-analyses describing varying ranges of co-infection and/or superinfection in patients with COVID-19. The concomitant infections described included other respiratory viruses, bacteria, including mycobacteria, fungi, as well as other, more unusual, pathogens. However, as will be seen in this review, there is often not a clear distinction made in the literature as to what the authors are referring to, whether true concomitant/co-infections or superinfections. In addition, possible mechanisms of the interactions between viral infections, including SARS-CoV-2, and other infections, particularly bacterial infections are discussed further. Lastly, the impact of these co-infections and superinfections in the severity of COVID-19 infections and their outcome is also described. Conclusion The current review describes varying rates of co-infections and/or superinfections in patients with COVID-19 infections, although often a clear distinction between the two is not clear in the literature. When they occur, these infections appear to be associated with both severity of COVID-19 as well as poorer outcomes.

First report of COVID-19-associated rhino-orbito-cerebral mucormycosis in pediatric patients with type 1 diabetes mellitus

“…In another systematic review of 101 cases of CAM, it was observed that 81% of the cases were from India and hyperglycemia at presentation was the predominant risk factor in 83% of the cases (15% had concomitant DKA), with history of corticisteroid treatment for COVID-19 in 76.3% [3] . While systemic steroids have been shown to offer survival benefit in COVID-19, their immunosuppressive action together with underlying diabetes and the complex cascade of SARS-CoV-2-induced immunological events, lead to an inflammatory state which might favour invasive fungal infections [ 1 , 18 ]. In the present series, both the patients had COVID-19 with uncontrolled diabetes and concomitant DKA.…”

“…Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a major public health problem worldwide. Recent reports suggest an increased incidence of secondary bacterial and fungal infections in COVID-19 patients [1] . While COVID-19 associated pulmonary aspergillosis (CAPA) has been extensively discussed, other invasive fungal diseases such as candidemia, trichosporonosis, fusariosis, histoplasmosis, cryptococcosis, coccidioidomycosis and currently, COVID-19 associated mucormycosis (CAM) have also been reported [ 2 , 3 ].…”

Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections

“…Secondary infections that provide additional stress for an already imbalanced immune system may further amplify inflammation. Typically, hosts are already infected by one or more persistent viruses and the virus-virus interplay may contribute to aberrant innate immune signaling [196]. Lastly, aberrant inflammation is further promoted by ageing of the immune system.…”

“…These secondary infections may further fuel the state of chronic inflammation, providing additional triggers to immune sensors. Incoming viral proteins may manipulate innate immune pathways, again leading to aberrant reactions, and thus eventually facilitate development of PAS [22,196]. Notably, acute infections often occur in hosts that are (acutely and/or latently) infected with multiple other viruses.…”

Incidence of Secondary Hemophagocytic Lymphohistiocytosis in Critically-Ill COVID-19 Patients

“…Prompt treatment of sHLH with broad immunosuppressive or immunomodulatory therapies such as glucocorticoids, cyclosporine, intravenous gamma globulin, anti-IL-6 and anti-IL-1 agents, or chemotherapeutics is important for favorable outcomes. However, use of immunosuppressant therapy in COVID-19 patients must be done cautiously, as co-infections can occur with COVID-19, and such infections have been associated with severity of SARS-CoV-2 as well as poor outcomes [ 8 ].…”