1. Euro J Clin Microbiol Inf Dis 2021; 40(3): 495–502.

Published online 2021 Jan 3. doi: 10.1007/s10096-020-04142-w

PMCID: PMC7778834
PMID: 33389263

Nosocomial infections associated to COVID-19 in the

intensive care unit: clinical characteristics and outcome
Tommaso Bardi, 1 Vicente Pintado,2 Maria Gomez-Rojo,1 Rosa
Escudero-Sanchez,2 Amal Azzam Lopez,1 Yolanda Diez-
Remesal,1 Nilda Martinez Castro,1 Patricia Ruiz-Garbajosa,3 and David
Pestaña1

Abstract

Bacterial and fungal co-infection has been reported in patients with COVID-19, but there is
limited experience on these infections in critically ill patients. The objective of this study
was to assess the characteristics and ouctome of ICU-acquired infections in COVID-19
patients. We conducted a retrospective single-centre, case-control study including 140
patients with severe COVID-19 admitted to the ICU between March and May 2020. We
evaluated the epidemiological, clinical, and microbiological features, and outcome of ICU-
acquired infections. Fifty-seven patients (40.7%) developed a bacterial or fungal
nosocomial infection during ICU stay. Infection occurred after a median of 9 days (IQR 5–
11) of admission and was significantly associated with the APACHE II score (p = 0.02).
There were 91 episodes of infection: primary (31%) and catheter-related (25%)
bloodstream infections were the most frequent, followed by pneumonia (23%),
tracheobronchitis (10%), and urinary tract infection (8%) that were produced by a wide
spectrum of Gram-positive (55%) and Gram-negative bacteria (30%) as well as fungi
(15%). In 60% of cases, infection was associated with septic shock and a significant
increase in SOFA score. Overall ICU mortality was 36% (51/140). Infection was
significantly associated with death (OR 2.7, 95% CI 1.2–5.9, p = 0.015) and a longer ICU stay
(p < 0.001). Bacterial and fungal nosocomial infection is a common complication of ICU
admission in patients with COVID-19. It usually presents as a severe form of infection, and
it is associated with a high mortality and longer course of ICU stay.
2. PLos One 2021 May 6;16(5):e0251170.

 doi: 10.1371/journal.pone.0251170. eCollection 2021. DOI: 10.1371/journal.pone.0251170

Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other
pathogens: A systematic review and meta-analysis

Jackson S Musuuza 1 2, Lauren Watson 1, Vishala Parmasad 1, Nathan Putman-Buehler 1, Leslie

Christensen 3, Nasia Safdar 1 2

Free PMC article

Abstract Introduction: The recovery of other pathogens in patients with SARS-CoV-2 infection
has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or
subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of
co-infection and superinfection are limited. The purpose of this study was to examine the
occurrence of co-infections and superinfections and their outcomes among patients with SARS-
CoV-2 infection.

Patients and methods: We searched literature databases for studies published from October 1,
2019, through February 8, 2021. We included studies that reported clinical features and
outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized
and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol
with PROSPERO as: CRD42020189763.

Results: Of 6639 articles screened, 118 were included in the random effects meta-analysis. The
pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%)
and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type
stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral
superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial
superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal
superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher
odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82-
5.99). Compared to those with co-infections, patients with superinfections had a higher
prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but
patients with co-infections had a greater average length of hospital stay than those with
superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2,
respectively).

Conclusions: Our study showed that as many as 19% of patients with COVID-19 have co-
infections and 24% have superinfections. The presence of either co-infection or superinfection
was associated with poor outcomes, including increased mortality. Our findings support the
need for diagnostic testing to identify and treat co-occurring respiratory infections among
patients with SARS-CoV-2 infection.

3. Chest 2021 Aug;160(2):454-465. doi: 10.1016/j.chest.2021.04.002. Epub 2021 Apr 20.

Hospital-Acquired Infections in Critically Ill Patients With COVID-19

Abstract

Background: Few small studies have described hospital-acquired infections (HAIs) occurring in
patients with COVID-19.

Research question: What characteristics in critically ill patients with COVID-19 are associated
with HAIs and how are HAIs associated with outcomes in these patients?

Study design and methods: Multicenter retrospective analysis of prospectively collected data
including adult patients with severe COVID-19 admitted to eight Italian hub hospitals from
February 20, 2020, through May 20, 2020. Descriptive statistics and univariate and multivariate
Weibull regression models were used to assess incidence, microbial cause, resistance patterns,
risk factors (ie, demographics, comorbidities, exposure to medication), and impact on outcomes
(ie, ICU discharge, length of ICU and hospital stays, and duration of mechanical ventilation) of
microbiologically confirmed HAIs.

Results: Of the 774 included patients, 359 patients (46%) demonstrated 759 HAIs (44.7
infections/1,000 ICU patient-days; 35% multidrug-resistant [MDR] bacteria). Ventilator-
associated pneumonia (VAP; n = 389 [50%]), bloodstream infections (BSIs; n = 183 [34%]), and
catheter-related BSIs (n = 74 [10%]) were the most frequent HAIs, with 26.0 (95% CI, 23.6-28.8)
VAPs per 1,000 intubation-days, 11.7 (95% CI, 10.1-13.5) BSIs per 1,000 ICU patient-days, and 4.7
(95% CI, 3.8-5.9) catheter-related BSIs per 1,000 ICU patient-days. Gram-negative bacteria
(especially Enterobacterales) and Staphylococcus aureus caused 64% and 28% of cases of VAP,
respectively. Variables independently associated with infection were age, positive end expiratory
pressure, and treatment with broad-spectrum antibiotics at admission. Two hundred thirty-four
patients (30%) died in the ICU (15.3 deaths/1,000 ICU patient-days). Patients with HAIs
complicated by septic shock showed an almost doubled mortality rate (52% vs 29%), whereas
noncomplicated infections did not affect mortality. HAIs prolonged mechanical ventilation
(median, 24 days [interquartile range (IQR), 14-39 days] vs 9 days [IQR, 5-13 days]; P < .001), ICU
stay (24 days [IQR, 16-41 days] vs 9 days [IQR, 6-14 days]; P = .003), and hospital stay (42 days
[IQR, 25-59 days] vs 23 days [IQR, 13-34 days]; P < .001).

Interpretation: Critically ill patients with COVID-19 are at high risk for HAIs, especially VAPs and
BSIs resulting from MDR organisms. HAIs prolong mechanical ventilation and hospitalization,
and HAIs complicated by septic shock almost double mortality.
4. Antimicrob Resist Inf Control 2021; 10: 119.

Published online 2021 Aug 12. doi: 10.1186/s13756-021-00988-7

Nosocomial infections among COVID-19 patients: an analysis of intensive care unit

surveillance data

Clara Chong Hui Ong,1

Abstract

Surveillance of nosocomial infections, like catheter-associated urinary tract infection

(CAUTI), central line-associated bloodstream infection, possible ventilator-associated
pneumonia and secondary bloodstream infections were observed to study the impact of
COVID-19 outbreak in ICUs from Tan Tock Seng Hospital and National Centre for Infectious
Diseases, Singapore between February and June 2020. Higher nosocomial infection rates
were observed in COVID-19 patients, although it was not statistically significant. Moreover,
COVID-19 patients seem to be more predisposed to CAUTI despite a higher proportion of
non-COVID-19 patients having urinary catheters. Thus, continued vigilance to ensure
adherence to IPC measures is needed.

5. J Intensive Care Med 2022 Oct;37(10):1353-1362.

doi: 10.1177/08850666221103495. Epub 2022 May 23.

Incidence, Risk Factors, and Prognosis of Bloodstream Infections in COVID-19 Patients in

Intensive Care: A Single-Center Observational Study

Ahmet Furkan Kurt 1,

Abstract

Background: Critically ill COVID-19 patients are prone to bloodstream infections (BSIs).

Aim: To evaluate the incidence, risk factors, and prognosis of BSIs developing in COVID-
19 patients in the intensive care unit (ICU).
Methods: Patients staying at least 48 h in ICU from 22 March 2020 to 25 May 2021 were
included. Demographic, clinical, and laboratory data were analyzed.

Results: The median age of the sample (n = 470) was 66 years (IQR 56.0-76.0), and 64%
were male. The three most common comorbidities were hypertension (49.8%), diabetes
mellitus (32.8%), and coronary artery disease (25.7%). Further, 252 BSI episodes
developed in 179 patients, and the BSI incidence rate was 50.2 (95% CI 44.3-56.7) per
1000 patient-days. The source of BSI is central venous catheter in 42.5% and lower
respiratory tract in 38.9% of the episodes. Acinetobacter baumannii (40%) and
carbapenem-resistant Klebsiella pneumoniae (21%) were the most common pathogens.
CRP levels were lower in patients receiving tocilizumab. Multivariable analysis revealed
that continuous renal replacement therapy, extracorporeal membrane oxygenation, and
treatment with a combination of methylprednisolone and tocilizumab were independent
risk factors for BSI. The estimated cumulative risk of developing first BSI episode was
50% after 6 days and 100% after 25 days. Of the 179 patients, 149 (83.2%) died, and a
statistically significant difference (p < 0.001) was found in the survival distribution in
favor of the group without BSI.

Conclusion: BSI is a common complication in COVID-19 patients followed in the ICU,

and it can lead to mortality. Failure in infection control measures, intensive
immunosuppressive treatments, and invasive interventions are among the main factors
leading to BSIs.

Keywords: COVID-19; ICU; bloodstream infection.

6. Pathogens 2023 Apr 19;12(4):620.

doi: 10.3390/pathogens12040620.

A Retrospective Assessment of Sputum Samples and Antimicrobial Resistance in COVID-

19 Patients

Talida Georgiana Cut

Abstract

Data on bacterial or fungal pathogens and their impact on the mortality rates of Western
Romanian COVID-19 patients are scarce. As a result, the purpose of this research was to
determine the prevalence of bacterial and fungal co- and superinfections in Western Romanian
adults with COVID-19, hospitalized in in-ward settings during the second half of the pandemic,
and its distribution according to sociodemographic and clinical conditions. The unicentric
retrospective observational study was conducted on 407 eligible patients. Expectorate sputum
was selected as the sampling technique followed by routine microbiological investigations. A
total of 31.5% of samples tested positive for Pseudomonas aeruginosa, followed by 26.2% having
co-infections with Klebsiella pneumoniae among patients admitted with COVID-19. The third
most common Pathogenic bacteria identified in the sputum samples was Escherichia coli,
followed by Acinetobacter baumannii in 9.3% of samples. Commensal human pathogens caused
respiratory infections in 67 patients, the most prevalent being Streptococcus penumoniae,
followed by methicillin-sensitive and methicillin-resistant Staphylococcus aureus. A total of 53.4%
of sputum samples tested positive for Candida spp., followed by 41.1% of samples
with Aspergillus spp. growth. The three groups with positive microbial growth on sputum
cultures had an equally proportional distribution of patients admitted to the ICU, with an
average of 30%, compared with only 17.3% among hospitalized COVID-19 patients with
negative sputum cultures (p = 0.003). More than 80% of all positive samples showed multidrug
resistance. The high prevalence of bacterial and fungal co-infections and superinfections in
COVID-19 patients mandates for strict and effective antimicrobial stewardship and infection
control policies.

Keywords: SARS-CoV-2; co-infection; multidrug resistance; outcome; superinfection.

7. Eur Rev Med Pharmacol Sci 2022 Mar;26(5):1753-1760.

doi: 10.26355/eurrev_202203_28245.

Are we aware of COVID-19-related acute kidney injury in intensive care units?

N Dereli 1, M Babayigit, O Menteş, F Koç, O Ari, E Doğan, E Onhan

Abstract

Objective: Coronavirus disease-19 (COVID-19) primarily affects the respiratory system.

In some cases, the heart, kidney, liver, circulatory system, and nervous system are also
affected. COVID-19-related acute kidney injury (AKI) occurs in more than 20% of
hospitalized patients and more than 50% of patients in the intensive care unit (ICU). In
this study, we aimed to review the prevalence of COVID-19-related acute kidney injury,
risk factors, hospital and ICU length of stay, the need for renal replacement therapy. We
also examined the effect of AKI on mortality in patients in the ICU that we treated
during a 1-year period.

Patients and methods: The files of patients with COVID-19 (n=220) who were treated
in our ICU between March 21st, 2020, and June 1st, 2021, were analyzed retrospectively.
Demographic data of the patients, laboratory data, and treatments were examined.
Patients were divided into two groups, group I patients without AKI and, group II
patients with AKI. The patients with AKI were evaluated according to the theKidney
Disease Improving Global Outcomes (KDIGO) classification and were graded.

Results: Of the 220 patients included in the study, 89 were female and 131 were male.
The mean age of patients with AKI (70.92±11.28 years) was statistically significantly
higher than among those without AKI (58.87±13.63 years) (p<0.001). In patients with
AKI, ICU length of stay, Acute Physiology and Chronic Health Evaluation (APACHE) II
scores, initial lactate levels, need for mechanical ventilation, duration of mechanical
ventilation, and secondary infection rates were found to be statistically significantly
higher. Discharge rates from the ICU in patients without AKI were statistically higher
(75.3% vs. 26.6%), and mortality rates were significantly higher in patients with AKI
(67.8% vs. 14.3%).

Conclusions: Various studies conducted have shown that patients with COVID-19 are at
risk for AKI, and this is closely related to age, sex, and disease severity. The presence of
AKI in patients with COVID-19 increases mortality, and this is more evident in patients
hospitalized in the ICU. In our study, the prevalence of AKI was higher in older patients
with high APACHE II scores and initial lactate levels. Comorbidities such as hypertension,
chronic kidney disease, and coronary artery disease in patients with AKI were higher
than in those without AKI.

8. World J Clin Cases 2023 Apr 6; 11(10): 2189–2200.

Published online 2023 Apr 6. doi: 10.12998/wjcc.v11.i10.2189

Liver manifestations in COVID-19 patients: A review article

Abstract

The coronavirus disease 2019 (COVID-19) initially presented as a disease that affected the
lungs. Then, studies revealed that it intricately affected disparate organs in the human
body, with the liver being one of the most affected organs. This review aimed to assess the
association between COVID-19 and liver function, shedding light on its clinical implication.
However, its exact pathophysiology remains unclear, involving many factors, such as active
viral replication in the liver cells, direct cytotoxic effects of the virus on the liver or adverse
reactions to viral antigens. Liver symptoms are mild-to-moderate transaminase elevation.
In some patients, with underlying liver disease, more serious outcomes are observed. Thus,
liver function should be meticulously considered in patients with COVID-19.

CONCLUSION

Despite the lack of evidence to elucidate the mechanisms of liver injury induced by COVID-
19 infection, this review provides a comprehensive approach to several theories
investigated. Further research is needed to clarify the factors in cause and determine
factors that might exacerbate liver injury in COVID-19 infected patients. Meticulous
attention should be kept on the liver of patients with COVID-19 infection, especially during
hospitalization. It is not clear yet on how to treat liver damage in patients with COVID-19
infection. There are no clear guidelines for proper treatment of liver injury in COVID-19
patients. Comparative studies might be needed for better evidence.

9. World J Gastroenterol 2023 Jan 14; 29(2): 241–256.

Published online 2023 Jan 14. doi: 10.3748/wjg.v29.i2.241

Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical
treatments

Shu-Wu Zhao, Yi-Ming Li, Yi-Lin Li, and Chen Su

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has been a serious threat to global
health for nearly 3 years. In addition to pulmonary complications, liver injury is not
uncommon in patients with novel COVID-19. Although the prevalence of liver injury varies
widely among COVID-19 patients, its incidence is significantly increased in severe cases.
Hence, there is an urgent need to understand liver injury caused by COVID-19. Clinical
features of liver injury include detectable liver function abnormalities and liver imaging
changes. Liver function tests, computed tomography scans, and ultrasound can help
evaluate liver injury. Risk factors for liver injury in patients with COVID-19 include male
sex, preexisting liver disease including liver transplantation and chronic liver disease,
diabetes, obesity, and hypertension. To date, the mechanism of COVID-19-related liver
injury is not fully understood. Its pathophysiological basis can generally be explained by
systemic inflammatory response, hypoxic damage, ischemia-reperfusion injury, and drug
side effects. In this review, we systematically summarize the existing literature on liver
injury caused by COVID-19, including clinical features, underlying mechanisms, and
potential risk factors. Finally, we discuss clinical management and provide
recommendations for the care of patients with liver injury.

CONCLUSION

Nearly 3 years later, there is still no sign that the COVID-19 pandemic is over. COVID has
long-term devastating effects involving multiple organs. Particular attention should be
given to liver injury associated with COVID-19. There is growing evidence that liver injury
is a typical long-term effect of COVID-19, especially in critically ill cases, and may require
monitoring after the patient is discharged. The exact incidence and underlying mechanism
of liver damage are not well known. Fortunately, most patients with mild liver damage
recover without special treatment. However, SLI is believed to worsen the prognosis and
increase mortality from COVID-19. Increased research efforts are needed to identify those
patients at higher risk of complications, better definition of liver injury, better
understanding of the pathophysiology, and effective therapies.