Secondary Infections in Critically Ill Patients With COVID-19

Giacomo Grasselli; Emanuele Cattaneo; Gaetano Florio


Crit Care. 2021;25(317) 

In This Article

Abstract and Introduction


This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at Further information about the Annual Update in Intensive Care and Emergency Medicine is available from


Since December 2019, when the first case of human transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in Wuhan (China), more than a hundred million confirmed cases of coronavirus disease 2019 (COVID-19) have been described worldwide, and the pandemic declared on March 11, 2020 by the World Health Organization is still ongoing.

The clinical spectrum of SARS-CoV-2 infection ranges from asymptomatic disease to severe disease requiring hospitalization and admission to the intensive care unit (ICU).[1] Recent multicenter studies showed that 5–32% of hospitalized patients with COVID-19 needed ICU admission,[2–5] mainly for acute respiratory distress syndrome (ARDS) requiring endotracheal intubation and invasive mechanical ventilation.[2–4,6,7] According to the available published data, the mortality of critically ill patients with COVID-19 ranges from 16 to 78%.[3,6–8]

For a number of reasons, patients with COVID-19 admitted to the ICU are at high risk of developing infectious complications during their ICU stay. First, they frequently develop multiple organ failure with need for vasopressors, renal replacement therapy (RRT) and, in some cases, extracorporeal membrane oxygenation support. The duration of mechanical ventilation and the ICU lengths of stay of these patients are therefore usually prolonged (up to 19 days for mechanical ventilation and up to 49 days for ICU length of stay[5,9]). Second, COVID-19 per se is associated with significant dysfunction of the patient's immune system. Multiple studies have shown the involvement of both innate and acquired immunity as a response to SARS-CoV-2 infection. Preliminary Chinese studies detected a reduction in both CD4+ T and CD8+ T lymphocyte counts, an increase in neutrophils and a reduction in interferon gamma (IFN-γ) serum concentrations.[10,11] Further studies confirmed these findings and showed a cytokine pattern characterized by excess pro-inflammatory molecules (cytokine storm[12]), inhibition of natural killer cells (NK and NKT) and cytotoxic lymphocytes, and morphological and phenotypical alterations of monocytes.[13–15] Third, after the publication of the results of the RECOVERY trial,[16] treatment with systemic corticosteroids has become standard of care in all patients requiring supplemental oxygen. In addition, a number of drugs aimed at blunting the immune system response to the viral infection (for example cytokine inhibitors [tocilizumab, anakinra, sarilumab] or complement inhibitors [eculizumab]) are frequently administered to these patients and several trials are ongoing to assess their efficacy. Finally, secondary bacterial and fungal infections as a complication of viral respiratory diseases have been described during previous pandemics (2002 severe acute respiratory syndrome [SARS],[17] 2009 swine influenza pandemic,[18] and 2012 Middle East respiratory syndrome [MERS][19]) and some studies have highlighted their role in increasing the severity of the viral pneumonia.[18]

A recent review of the literature showed that the incidence of co-infections (i.e., infections detected at admission) in patients with COVID-19 is less than in previous pandemics.[20] Data on secondary infections (i.e., infections acquired during the course of ICU stay) are scarce. The aim of the present chapter is to summarize the available evidence on the epidemiology, risk factors, impact on outcome and principles of treatment of secondary infections in critically ill patients with COVID-19