Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study

ObjectivesTo describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19).MethodsWe performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records.ResultsOf a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes.ConclusionsCo-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies.     

COVID-19 and liver dysfunction: A systematic review and meta-analysis of retrospective studies

Recently, Coronavirus Disease 2019 (COVID-19) pandemic is the most significant global health crisis. In this study, we conducted a meta-analysis to find the association between liver injuries and the severity of COVID-19 disease. Online databases, including PubMed, Web of Science, Scopus, and Science direct, were searched to detect relevant publications up to 16 April 2020. Depending on the heterogeneity between studies, a fixed- or random-effects model was applied to pool data. Publication bias Egger's test was also performed. Meta-analysis of 20 retrospective studies (3428 patients), identified that patients with a severe manifestation of COVID-19 exhibited significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin values with prolonged prothrombin time. Furthermore, lower albumin level was associated with a severe presentation of COVID-19. Liver dysfunction was associated with a severe outcome of COVID-19 disease. Close monitoring of the occurrence of liver dysfunction is beneficial in early warning of unfavorable outcomes.     

Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting

ObjectivesTo investigate the incidence of bacterial and fungal coinfection of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this retrospective observational study across two London hospitals during the first UK wave of coronavirus disease 2019 (COVID-19).MethodsA retrospective case series of hospitalized patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (20 February–20 April 2020; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza-positive patients admitted during the 2019–2020 flu season. Patient demographics, microbiology and clinical outcomes were analysed.ResultsA total of 836 patients with confirmed SARS-CoV-2 were included; 27 (3.2%) of 836 had early confirmed bacterial isolates identified (0–5 days after admission), rising to 51 (6.1%) of 836 throughout admission. Blood cultures, respiratory samples, pneumococcal or Legionella urinary antigens and respiratory viral PCR panels were obtained from 643 (77%), 110 (13%), 249 (30%), 246 (29%) and 250 (30%) COVID-19 patients, respectively. A positive blood culture was identified in 60 patients (7.1%), of which 39 were classified as contaminants. Bacteraemia resulting from respiratory infection was confirmed in two cases (one each community-acquired Klebsiella pneumoniae and ventilator-associated Enterobacter cloacae). Line-related bacteraemia was identified in six patients (three Candida, two Enterococcus spp. and one Pseudomonas aeruginosa). All other community-acquired bacteraemias (n = 16) were attributed to nonrespiratory infection. Zero concomitant pneumococcal, Legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; Staphylococcus aureus was the most common respiratory pathogen isolated in community-acquired coinfection (4/24; 16.7%), with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n = 3) were attributed to line-related infections. Comparable rates of positive coinfection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141; 1.4%), respiratory cultures (10/38; 26.3%) and pneumococcal-positive antigens (1/19; 5.3%) were low.ConclusionsWe found a low frequency of bacterial coinfection in early COVID-19 hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.     

COVID-19 patients benefit from early antiviral treatment: A comparative,retrospective study

The outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2, started in December 2019, Wuhan, China. We aimed to figure out the time-point and duration of using antiviral drugs for receiving the maximal effects in patients with COVID-19. In this study, we enrolled 129 confirmed COVID-19 mild to moderate patients who had been treated with antiviral drugs during their hospitalization in Wuhan Union Hospital China. The patients were divided into an early antiviral treatment group and late antiviral treatment group. The demographic data, laboratory tests, the virus clearance time, chest computed tomography scans, and so forth were extracted, calculated, and compared between two groups. Our data showed that the median time from illness onset to initiation of antiviral treatment was 6 days in all patients. The group with early antiviral treatment demonstrated 7 days shorter in the virus clearance time when compared to the group with late antiviral treatment. After virus clearance, the group with early antiviral treatment showed milder illness than the group with late antiviral treatment. Early antiviral treatment could effectively shorten the virus clearance time, and prevent the rapid progression of COVID-19. Therefore, the COVID-19 patients should receive combined therapies with antiviral treatment at an early stage.     

Clinical characteristics and risk factors for 28-day mortality in critically ill patients with COVID-19: a retrospective cohort study

BackgroundTo date, the coronavirus disease 2019 (COVID-19) caused more than 2.6 million deaths all around the world. Risk factors for mortality remain unclear. The primary aim was to determine the independent risk factors for 28-day mortality.Materials and MethodsIn this retrospective cohort study, critically ill patients (≥ 18 years) who were admitted to the intensive care unit due to COVID-19 were included. Patient characteristics, laboratory data, radiologic findings, treatments, and complications were analyzed in the study.ResultsA total of 249 patients (median age 71, 69.1% male) were included in the study. 28-day mortality was 67.9% (n = 169). The median age of deceased patients was 75 (66–81). Of them, 68.6% were male. Cerebrovascular disease, dementia, chronic kidney disease, and malignancy were significantly higher in the deceased group. In the multivariate analysis, sepsis/septic shock (OR, 15.16, 95% CI, 3.96–58.11, p < 0.001), acute kidney injury (OR, 4.73, 95% CI, 1.55–14.46,p = 0.006), acute cardiac injury (OR, 9.76, 95% CI, 1.84–51.83, p = 0.007), and chest CT score higher than 15 (OR, 4.49, 95% CI, 1.51-13.38, p = 0.007) were independent risk factors for 28-day mortality.ConclusionEarly detection of the risk factors and the use of chest CT score might improve the outcomes in patients with COVID-19.     

Impact of COVID-19 and malaria coinfection on clinical outcomes: a retrospective cohort study

ObjectivesDespite the possibility of concurrent infection with COVID-19 and malaria, little is known about the clinical course of coinfected patients. We analysed the clinical outcomes of patients with concurrent COVID-19 and malaria infection.MethodsWe conducted a retrospective cohort study that assessed prospectively collected data of all patients who were admitted between May and December 2020 to the Universal COVID-19 treatment center (UCTC), Khartoum, Sudan. UCTC compiled demographic, clinical, laboratory (including testing for malaria), and outcome data in all patients with confirmed COVID-19 hospitalized at that clinic. The primary outcome was all-cause mortality during the hospital stay. We built proportional hazard Cox models with malaria status as the main exposure and stepwise adjustment for age, sex, cardiovascular comorbidities, diabetes, and hypertension.ResultsWe included 591 patients with confirmed COVID-19 diagnosis who were also tested for malaria. Mean (SD) age was 58 (16.2) years, 446/591 (75.5%) were males. Malaria was diagnosed in 270/591 (45.7%) patients. Most malaria patients were infected by Plasmodium falciparum (140/270; 51.9%), while 121/270 (44.8%) were coinfected with Plasmodium falciparum and Plasmodium vivax. Median follow-up was 29 days. Crude mortality rates were 10.71 and 5.87 per 1000 person-days for patients with and without concurrent malaria, respectively. In the fully adjusted Cox model, patients with concurrent malaria and COVID-19 had a greater mortality risk (hazard ratio 1.43, 95% confidence interval 1.21-1.69).DiscussionCoinfection with COVID-19 and malaria is associated with increased all-cause in-hospital mortality compared to monoinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).     

Neurologic manifestations associated with COVID-19: a multicentre registry

ObjectivesTo provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsWe conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March–April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible.ResultsWe included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53–72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19–associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3–8) days in COVID-19–associated encephalopathy, 7 (5–10) days in encephalitis, 12 (7–18) days in acute ischaemic cerebrovascular syndrome and 18 (15–28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17–34) days with a high short-term mortality rate (28/222, 12.6%).ConclusionsClinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.     

Effects of tocilizumab on mortality in hospitalized patients with COVID-19: a multicentre cohort study

ObjectivesTocilizumab has been proposed as a candidate therapy for patients with severe coronavirus disease 2019 (COVID-19), especially among those with higher systemic inflammation. We investigated the association between receipt of tocilizumab and mortality in a large cohort of hospitalized patients.MethodsIn this cohort study of patients hospitalized with COVID-19 in Spain, the primary outcome was time to death and the secondary outcome time to intensive care unit (ICU) admission or death. We used inverse probability weighting to fit marginal structural models adjusted for time-varying covariates to determine the causal relationship between receipt of tocilizumab and outcome.ResultsData from 1229 patients were analysed, with 261 patients (61 deaths) in the tocilizumab group and 969 patients (120 deaths) in the control group. In the adjusted marginal structural models, a significant interaction between receipt of tocilizumab and high C-reactive protein (CRP) levels was detected. Tocilizumab was associated with decreased risk of death (adjusted hazard ratio 0.34, 95% confidence interval 0.16–0.72, p 0.005) and ICU admission or death (adjusted hazard ratio 0.39, 95% confidence interval 0.19–0.80, p 0.011) among patients with baseline CRP >150 mg/L but not among those with CRP ≤150 mg/L. Exploratory subgroup analyses yielded point estimates that were consistent with these findings.ConclusionsIn this large observational study, tocilizumab was associated with a lower risk of death or ICU admission or death in patients with higher CRP levels. While the results of ongoing clinical trials of tocilizumab in patients with COVID-19 will be important to establish its safety and efficacy, our findings have implications for the design of future clinical trials.     

Clinical characteristics of COVID-19 in patients with preexisting ILD: A retrospective study in a single center in Wuhan,China

Since the outbreak of 2019 novel coronavirus (SARS-CoV-2) pneumonia, many patients with underlying disease, such as interstitial lung disease (ILD), were admitted to Tongji hospital in Wuhan, China. To date, no data have ever been reported to reflect the clinical features of Corona Virus Disease 2019 (COVID-19) among these patients with preexisting ILD. We analyzed the incidence and severity of COVID-19 patients with ILD among 3201 COVID-19 inpatients, and compared two independent cohorts of COVID-19 patients with pre-existing ILD (n = 28) and non-ILD COVID-19 patients (n = 130). Among those 3201 COVID-19 inpatients, 28 of whom were COVID-19 with ILD (0.88%). Fever was the predominant symptom both in COVID-19 with ILD (81.54%) and non-ILD COVID-19 patients (72.22%). However, COVID-19 patients with ILD were more likely to have cough, sputum, fatigue, dyspnea, and diarrhea. A very significantly higher number of neutrophils, monocytes, interleukin (IL)-8, IL-10, IL-1β, and D-Dimer was characterized in COVID-19 with ILD as compared to those of non-ILD COVID-19 patients. Furthermore, logistic regression models showed neutrophils counts, proinflammatory cytokines (tumor necrosis factor-alpha, IL6, IL1β, IL2R), and coagulation dysfunction biomarkers (D-Dimer, PT, Fbg) were significantly associated with the poor clinical outcomes of COVID-19. ILD patients could be less vulnerable to SARS-CoV-2. However, ILD patients tend to severity condition after being infected with SARS-CoV-2. The prognosis of COVID-19 patients with per-existing ILD is significantly worse than that of non-ILD patients. And more, aggravated inflammatory responses and coagulation dysfunction appear to be the critical mechanisms in the COVID-19 patients with ILD.     

Risk factors associated with COVID-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort

ObjectivesThe main objective of this study was to determine the incidence of invasive pulmonary aspergillosis (IPA) in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and to describe the patient characteristics associated with IPA occurrence and to evaluate its impact on prognosis.MethodsWe conducted a retrospective cohort study including all successive COVID-19 patients, hospitalized in four ICUs, with secondary deterioration and one or more respiratory samples sent to the mycology department. We used a strengthened IPA testing strategy including seven mycological criteria. Patients were classified as probable IPA according to the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) classification if immunocompromised, and according to the recent COVID-19-associated IPA classification otherwise.ResultsProbable IPA was diagnosed in 21 out of the 366 COVID-19 patients (5.7%) admitted to the ICU and in the 108 patients (19.4%) who underwent respiratory sampling for deterioration. No significant differences were observed between patients with and without IPA regarding age, gender, medical history and severity on admission and during hospitalization. Treatment with azithromycin for ≥3 days was associated with the diagnosis of probable IPA (odds ratio 3.1, 95% confidence interval 1.1–8.5, p = 0.02). A trend was observed with high-dose dexamethasone and the occurrence of IPA. Overall mortality was higher in the IPA patients (15/21, 71.4% versus 32/87, 36.8%, p < 0.01).ConclusionIPA is a relatively frequent complication in severe COVID-19 patients and is responsible for increased mortality. Azithromycin, known to have immunomodulatory properties, may contribute to increase COVID-19 patient's susceptibility to IPA.     

Cardiac Troponin I association with critical illness and death risk in 726 seriously ill COVID-19 patients: A retrospective cohort study

Background: For coronavirus disease 2019 (COVID-19), early identification of patients with serious symptoms at risk of critical illness and death is important for personalized treatment and balancing medical resources.Methods: Demographics, clinical characteristics, and laboratory tests data from 726 patients with serious COVID-19 at Tongji Hospital (Wuhan, China) were analyzed. Patients were classified into critical group (n = 174) and severe group (n= 552), the critical group was sub-divided into survivors (n = 47) and non-survivors (n = 127).Results: Multivariable analyses revealed the risk factors associated with critical illness in serious patients were: Advanced age, high respiratory rate (RR), high lactate dehydrogenase (LDH) level, high hypersensitive cardiac troponin I (hs-cTnI) level, and thrombocytopenia on admission. High hs-cTnI level was the independent risk factor of mortality among critically ill patients in the unadjusted and adjusted models. ROC curves demonstrated that hs-cTnI and LDH were predictive factors for critical illness in patients with serious COVID-19 whereas procalcitonin and D-Dimer with hs-cTnI and LDH were predictive parameters in mortality risk.Conclusions: Advanced age, high RR, LDH, hs-cTnI, and thrombocytopenia, constitute risk factors for critical illness among patients with serious COVID-19, and the hs-cTnI level helps predict fatal outcomes in critically ill patients.     

Risk factors for illness severity in patients with COVID-19 pneumonia: a prospective cohort study

Background: Although COVID-19 pneumonia is spreading internationally, knowledge regarding the factors associated with the illness severity of patients remains limited. We aimed to identify the factors associated with the disease severity of patients with COVID-19 pneumonia induced by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Methods: We prospectively enrolled a single-center case series of adult patients with COVID-19 admitted to the Infectious Disease Hospital of Jining, Jining City, Shandong Province, China, from January 24 to March 1, 2020. Demographics, clinical characteristics, and laboratory findings were compared to investigate the risk factors related with the disease severity of COVID-19 pneumonia patients.Results: We included a total of 78 patients with COVID-19 pneumonia, of whom 6 had the severe type. As compared to a moderately ill cohort, our analysis showed that shortness of breath, fatigue, longer days from illness onset to diagnosis confirmed, neutrophil percentages > 70%, neutrophil counts > 6.3 × 10⁹/L, lymphocyte percentages < 20%, lymphocyte counts < 1.0 × 10⁹/L, platelet < 100 × 10⁹/L, C-reactive protein (CRP) > 10 mg/L, neutrophil to platelet ratio (NPR) > 2.3, neutrophil to lymphocyte ratio (NLR) > 3.9, aspartate aminotransferase (AST) > 40 U/L, albumin < 40 g/L, lactate dehydrogenase (LDH) > 245 U/L, and glucose > 6.1 mmol/L were predictors of disease severity in COVID-19 pneumonia. In the sex-, age-, and comorbid illness-matched case-control study, neutrophil percentages > 70%, neutrophil counts > 6.3 × 10⁹/L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L remained associated with the early detection and identification of severe patients.Conclusion: We demonstrated that neutrophil percentages > 70%, neutrophil counts > 6.3 × 10⁹/L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L might predict the severity of illness in patients with COVID-19 pneumonia.     

Clinical course of patients on maintenance hemodialysis and COVID-19: a retrospective longitudinal study

Coronavirus Disease 2019 (COVID-19) emerges as a global pandemic and there is a lack of evidence about the clinical course and outcome of patients on maintenance hemodialysis (MHD). Here we conducted a retrospective longitudinal study aimed to analyze the clinical features and outcome of MHD patients hospitalized with COVID-19. Of 3126 inpatients with COVID-19 at 3 Branches of Wuhan Tongji Hospital from Jan 18th to Mar 9th, 2020, 19 patients were undergoing maintenance hemodialysis. Among the 19 MHD patients with COVID-19, 6 patients (31.6%) died, and 13 patients (68.4%) were able to be discharged. Baseline characteristics, clinical courses, laboratory findings, and dynamic trajectories of major laboratory markers were compared between survivors and nonsurvivors. According to our findings, MHD patients with COVID-19 who experienced non-surviving outcome had more elevated CRP, IL6 and procalcitonin as well as fibrinogen levels at various points compared to survivors. Thus the dysregulation of immune response as well as coagulation abnormalities might be highly involved in the pathological process of COVID-19, contributing to the poor prognosis in MHD patients.     

Clinical and epidemiological characteristics of 320 deceased patients with COVID-19 in an Italian Province: A retrospective observational study

Studies have described clinical features of patients with coronavirus disease (COVID-19). However, limited data concerning the clinical characteristics of the Italian deaths are available. We aim to describe the clinical and epidemiological characteristics of 320 deceased from the Italian experience. We retrospectively collected all consecutive non-survivor patients with laboratory-confirmed COVID-19 infection admitted to the Emergency Rooms (ERs) Piacenza Hospital Network during the first month of COVID-19 pandemic in Italy. Clinical history, comorbidities, laboratory findings and treatment were recorded for each patient. A total of 1050 patients with confirmed COVID-19 pneumonia were admitted to the ERs between 24 February and 22 March 2020. Three hundred and twenty (30.5%) patients died with a median age of 78.0 years, 205 (64%) non-survivors were above 65 years old, 230 (71.9%) were male. Non-survivor patients showed frequently several coexisting medical conditions, with hypertension being the most common comorbidity (235 patients, 73.4%). The in-hospital mortality did not change during the progression of the pandemic. In this retrospective Italian study, most of COVID-19 deceased patients were elderly male aged over than 65 years. Hypertension was the most common coexisting disease. In-hospital mortality was high and showed no variation during the first month of the COVID-19 italian epidemic.     

Impact of comorbidities on patients with COVID-19: A large retrospective study in Zhejiang,China

Coronavirus disease 2019 (COVID-19) has become a serious public health problem worldwide. Here, we stratified COVID-19 patients based on their comorbidities to assess their risk of serious adverse outcomes. We collected 856 hospitalized cases diagnosed with COVID-19 from 17 January to 7 February 2020, in Zhejiang Province, and analyzed their comorbidities and composite endpoint (including admission to intensive care unit owing to disease progression, shock, invasive ventilation, and death) to determine the relationship between comorbidities and adverse outcomes. The median age of patients was 46 (36-56) years; 439 (51.3%) were men, 242 (28.3%) had comorbidities, and 152 (17.8%) had two or more comorbidities. The most common comorbidity was hypertension (142 [16.6%]), followed by diabetes (64 [7.5%]). Of the 856 patients, there are 154 (18.0%) severe cases. Thirty-two (3.7%) reached composite endpoints, of which 22 (9.1%) were from the comorbidity group and 10 (1.6%) from the non-comorbidity group (P < .001). After adjusting for age and gender status, the risk of reaching the composite endpoint was higher in the group with comorbidity than in that without comorbidity (hazard ratio [HR] 3.04, 95% confidence interval [CI]: 1.40-6.60). HR values for patients with one, two, and three or more comorbidities were 1.61 (95% CI: 0.44-5.91), 3.44 (95% CI: 1.31-9.08), and 6.90 (95% CI: 2.69-17.69), respectively. COVID-19 patients with comorbidities had worse clinical outcomes as compared with those without any comorbidity. The higher the number of comorbidities, the greater was the risk of serious adverse outcomes.