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.     

Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis

BackgroundBacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection in patients infected with SARS-CoV-2 is not well understood.AimsTo determine the prevalence of bacterial co-infection (at presentation) and secondary infection (after presentation) in patients with COVID-19.SourcesWe performed a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020. Studies were included if they (a) evaluated patients with confirmed COVID-19 and (b) reported the prevalence of acute bacterial infection.ContentData were extracted by a single reviewer and cross-checked by a second reviewer. The main outcome was the proportion of COVID-19 patients with an acute bacterial infection. Any bacteria detected from non-respiratory-tract or non-bloodstream sources were excluded. Of 1308 studies screened, 24 were eligible and included in the rapid review representing 3338 patients with COVID-19 evaluated for acute bacterial infection. In the meta-analysis, bacterial co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI 0.4–6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6–18.9%). The overall proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3–9.5%). Bacterial infection was more common in critically ill patients (8.1%, 95%CI 2.3–13.8%). The majority of patients with COVID-19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%).ImplicationsBacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. The majority of these patients may not require empirical antibacterial treatment.     

Secondary infections in patients hospitalized with COVID-19: incidence and predictive factors

ObjectivesThe aim of our study was to describe the incidence and predictive factors of secondary infections in patients with coronavirus disease 2019 (COVID-19).MethodsThis was a cohort study of patients hospitalized with COVID-19 at IRCCS San Raffaele Hospital between 25th February and 6th April 2020 (NCT04318366). We considered secondary bloodstream infections (BSIs) or possible lower respiratory tract infections (pLRTIs) occurring 48 hours after hospital admission until death or discharge. We calculated multivariable Fine–Gray models to assess factors associated with risk of secondary infections.ResultsAmong 731 patients, a secondary infection was diagnosed in 68 patients (9.3%); 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. The overall 28-day cumulative incidence was 16.4% (95%CI 12.4–21.0%). Most of the BSIs were due to Gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among Gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were caused mainly by Gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count (≤0.7 versus >0.7 per 10⁹/L, subdistribution hazard ratios (sdHRs) 1.93, 95%CI 1.11–3.35), baseline PaO₂/FiO₂ (per 100 points lower: sdHRs 1.56, 95%CI 1.21–2.04), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51, 95%CI 1.04–6.05).ConclusionsPatients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia were identified as risk factors for secondary infections.     

Predictors and microbiology of respiratory and bloodstream bacterial infection in patients with COVID-19: living rapid review update and meta-regression

BackgroundThe prevalence of bacterial infection in patients with COVID-19 is low, however, empiric antibiotic use is high. Risk stratification may be needed to minimize unnecessary empiric antibiotic use.ObjectiveTo identify risk factors and microbiology associated with respiratory and bloodstream bacterial infection in patients with COVID-19.Data sourcesWe searched MEDLINE, OVID Epub and EMBASE for published literature up to 5 February 2021.Study eligibility criteriaStudies including at least 50 patients with COVID-19 in any healthcare setting.MethodsWe used a validated ten-item risk of bias tool for disease prevalence. The main outcome of interest was the proportion of COVID-19 patients with bloodstream and/or respiratory bacterial co-infection and secondary infection. We performed meta-regression to identify study population factors associated with bacterial infection including healthcare setting, age, comorbidities and COVID-19 medication.ResultsOut of 33 345 studies screened, 171 were included in the final analysis. Bacterial infection data were available from 171 262 patients. The prevalence of co-infection was 5.1% (95% CI 3.6–7.1%) and secondary infection was 13.1% (95% CI 9.8–17.2%). There was a higher odds of bacterial infection in studies with a higher proportion of patients in the intensive care unit (ICU) (adjusted OR 18.8, 95% CI 6.5–54.8). Female sex was associated with a lower odds of secondary infection (adjusted OR 0.73, 95% CI 0.55–0.97) but not co-infection (adjusted OR 1.05, 95% CI 0.80–1.37). The most common organisms isolated included Staphylococcus aureus, coagulase-negative staphylococci and Klebsiella species.ConclusionsWhile the odds of respiratory and bloodstream bacterial infection are low in patients with COVID-19, meta-regression revealed potential risk factors for infection, including ICU setting and mechanical ventilation. The risk for secondary infection is substantially greater than the risk for co-infection in patients with COVID-19. Understanding predictors of co-infection and secondary infection may help to support improved antibiotic stewardship in patients with COVID-19.     

Risk factors for disease severity,unimprovement, and mortality in COVID-19 patients in Wuhan,China

ObjectiveIn December 2019, coronavirus disease (COVID-19) emerged in Wuhan. However, the characteristics and risk factors associated with disease severity, unimprovement and mortality are unclear and our objective is to throw some light on these.MethodsAll consecutive patients diagnosed with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 11 to February 6, 2020, were enrolled in this retrospective cohort study.ResultsA total of 663 COVID-19 patients were included in this study. Among these, 247 (37.3%) had at least one kind of chronic disease; 0.5% of the patients (n = 3) were diagnosed with mild COVID-19, while 37.8% (251/663), 47.5% (315/663), and 14.2% (94/663) were in moderate, severe, and critical conditions, respectively. In our hospital, during follow-up 251 of 663 patients (37.9%) improved and 25 patients died, a mortality rate of 3.77%. Older patients (>60 years old) and those with chronic diseases were prone to have a severe to critical COVID-19 condition, to show unimprovement, and to die (p <0.001, <0.001). Multivariate logistic regression analysis identified being male (OR = 0.486, 95%CI 0.311–0.758; p 0.001), having a severe COVID-19 condition (OR = 0.129, 95%CI 0.082–0.201; p <0.001), expectoration (OR = 1.796, 95%CI 1.062–3.036; p 0.029), muscle ache (OR = 0.309, 95%CI 0.153–0.626; p 0.001), and decreased albumin (OR = 1.929, 95%CI 1.199–3.104; p 0.007) as being associated with unimprovement in COVID-19 patients.ConclusionMale sex, a severe COVID-19 condition, expectoration, muscle ache, and decreased albumin were independent risk factors which influence the improvement of COVID-19 patients.     

Profile of co-infections & secondary infections in COVID-19 patients at a dedicated COVID-19 facility of a tertiary care Indian hospital: Implication on antimicrobial resistance

BackgroundThe COVID-19 pandemic has raised concerns over secondary infections because it has limited treatment options and empiric antimicrobial treatment poses serious risks of aggravating antimicrobial resistance (AMR). Studies have shown that COVID-19 patients are predisposed to develop secondary infections. This study was conducted to ascertain the prevalence and profiles of co- & secondary infections in patients at the COVID-19 facility in North India.MethodsWe studied the profile of pathogens isolated from 290 clinical samples. Bacterial and fungal pathogens were identified, and antimicrobial susceptibility was determined by the Vitek2® system. Additionally, respiratory samples were tested for any viral/atypical bacterial co-infections and the presence of AMR genes by FilmArray test. The clinical and outcome data of these patients were also recorded for demographic and outcome measures analyses.ResultsA total of 151 (13%) patients had secondary infections, and most got infected within the first 14 days of hospital admission. Patients aged >50 years developed severe symptoms (p = 0.0004) and/or had a fatal outcome (p = 0.0005). In-hospital mortality was 33%.K.pneumoniae (33.3%) was the predominant pathogen, followed by A. baumannii (27.1%). The overall resistance was up to 84%.Majority of the organisms were multidrug-resistant (MDR) harbouring MDR genes.ConclusionA high rate of secondary infections with resistant pathogens in COVID-19 patients highlights the importance of antimicrobial stewardship programs focussing on supporting the optimal selection of empiric treatment and rapid-de-escalation, based on culture reports.     

More than loss of taste and smell: burning watering eyes in coronavirus disease 2019

ObjectivesTo evaluate ocular symptoms in European non-hospitalized patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and to investigate associations with the demographic data as well as nasal and general physical symptoms.MethodsIn this prospective, observational study, 108 non-hospitalized patients with PCR-confirmed SARS-CoV-2 infection not requiring intensive care were asked about disease-associated ocular symptoms, demographic data, as well as general physical and nasal symptoms using a standardized questionnaire. Total ocular symptom score (TOSS) was evaluated during and, retrospectively, before development of coronavirus disease 2019 (COVID-19). Associations between TOSS and demographic data as well as general and nasal symptoms were evaluated.ResultsSeventy-five of the 108 COVID-19 patients (69.4%) had at least one ocular symptom during COVID-19. The most common symptoms included burning sensations in 39 (36.1%), epiphora in 37 (34.3%) and redness in 28 (25.9%), compatible with conjunctivitis. These symptoms occurred 1.96 ± 3.17 days after the beginning of COVID-19 and were mild. TOSS was significantly higher during COVID-19 (1.27 ± 1.85) than before the infection (0.33 ± 1.04; p < 0.001). There were no significant associations between TOSS and gender (β coefficient –0.108; p 0.302), age (–0.024; p 0.816), rhinorrhoea (–0.127; p 0.353), nasal itching (–0.026; p 0.803), sneezing (0.099; p 0.470), nasal congestion (–0.012; p 0.930), cough (–0.079; p 0.450), headache (0.102; p 0.325), sore throat (0.208; p 0.052), or fever (0.094; p 0.361).ConclusionsOcular involvement in European non-hospitalized individuals with COVID-19 seems to be highly underestimated. Overall, these ocular symptoms, including burning sensations, epiphora and redness, seem to be mild and to not need treatment.     

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.     

The interface between COVID-19 and bacterial healthcare-associated infections

BackgroundA wide range of bacterial infections occur in coronavirus disease 2019 (COVID-19) patients, particularly in those with severe coronaviral disease. Some of these are community-acquired co-infections.ObjectiveTo review recent data that indicate the occurrence of hospital-onset bacterial infections, including with antibiotic-resistant isolates, in COVID-19 patients.SourcesUsing PubMed, the literature was searched using terms including: ‘COVID-19’; ‘SARS-CoV-2’; ‘bacterial infection’; ‘healthcare-associated infection’; ‘antibiotic resistance’; ‘antimicrobial resistance’; ‘multi-drug resistance’; ‘Streptococcus’; ‘Staphylococcus’; ‘Pseudomonas’; ‘Escherichia’; ‘Klebsiella’; ‘Enterococcus’; ‘Acinetobacter’; ‘Haemophilus’; ‘MRSA’; ‘VRE’; ‘ESBL’; ‘NDM-CRE’; ‘CR-Ab’; ‘VRSA’; ‘MDR’.ContentThere is a growing number of reports of bacterial infections acquired by patients with severe COVID-19 after hospital admission. Antibiotic-resistant pathogens found to cause healthcare-associated infections (HAIs) in COVID-19 patients include methicillin-resistant Staphylococcus aureus, New Delhi metallo-β-lactamase-producing carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, extended-spectrum β-lactamase Klebsiella pneumoniae and vancomycin-resistant enterococci. COVID-19 has impacted bacterial HAIs in a number of ways with an increase in the incidence of New Delhi metallo-β-lactamase-producing carbapenem-resistant Enterobacterales and carbapenem-resistant A. baumannii reported at some hospital sites compared with before the pandemic. Recommended guidelines for antimicrobial stewardship in COVID-19 patient treatment are discussed regarding minimization of empiric broad-spectrum antibiotic use. Other studies have reported a decrease in methicillin-resistant S. aureus and vancomycin-resistant enterococci cases, which has been attributed to enhanced infection prevention and control practices introduced to minimize intra-hospital spread of COVID-19.ImplicationsPoorer outcomes have been observed in hospitalized COVID-19 patients with an antibiotic-resistant infection. Although heightened IPC measures have been accompanied by a reduction in some HAIs at specific sites, in other situations, COVID-19 has been associated with an increase in bacterial HAI incidence. Further research is needed to define the cost–benefit relationship of maintaining COVID-19-related infection prevention and control protocols beyond the pandemic to reduce the burden of HAIs. In addition, the longer-term impact of high usage of certain broad-spectrum antibiotics during the COVID-19 pandemic requires evaluation.     

Clinical course and factors associated with outcomes among 1904 patients hospitalized with COVID-19 in Germany: an observational study

ObjectivesIn Germany the coronavirus disease 2019 (COVID-19) pandemic situation is unique among large European countries in that incidence and case fatality rate are distinctly lower. We describe the clinical course and examine factors associated with outcomes among patients hospitalized with COVID-19 in Germany.MethodsIn this retrospective cohort study we included patients with COVID-19 admitted to a national network of German hospitals between February 12 and June 12, 2020. We examined demographic characteristics, comorbidities and clinical outcomes.ResultsWe included 1904 patients with a median age of 73 years, 48.5% (924/1904) of whom were female. The mortality rate was 17% (317/1835; 95% confidence interval (95%CI) 16–19), the rate of admission to the intensive care unit (ICU) was 21% (399/1860; 95%CI 20–23), and the rate of invasive mechanical ventilation was 14% (250/1850: 95%CI 12–15). The most prominent risk factors for death were male sex (hazard ratio (HR) 1.45; 95%CI 1.15–1.83), pre-existing lung disease (HR 1.61; 95%CI 1.20–2.16), and increased patient age (HR 4.11 (95%CI 2.57–6.58) for age >79 years versus <60 years). Among patients admitted to the ICU, the mortality rate was 29% (109/374; 95%CI 25–34) and higher in ventilated (33% [77/235; 95%CI 27–39]) than in non-ventilated ICU patients (23%, 32/139; 95%CI 16–30; p < 0.05).ConclusionsIn this nationwide series of patients hospitalized with COVID-19 in Germany, in-hospital and ICU mortality rates were substantial. The most prominent risk factors for death were male sex, pre-existing lung disease, and greater patient age.     

Clinical course and outcomes of critically ill patients with COVID-19 infection: a systematic review

ObjectivesCoronavirus disease 19 (COVID-19) is a major cause of hospital admission and represents a challenge for patient management during intensive care unit (ICU) stay. We aimed to describe the clinical course and outcomes of COVID-19 pneumonia in critically ill patients.MethodsWe performed a systematic search of peer-reviewed publications in MEDLINE, EMBASE and the Cochrane Library up to 15th August 2020. Preprints and reports were also included if they met the inclusion criteria. Study eligibility criteria were full-text prospective, retrospective or registry-based publications describing outcomes in patients admitted to the ICU for COVID-19, using a validated test. Participants were critically ill patients admitted in the ICU with COVID-19 infection.ResultsFrom 32 articles included, a total of 69 093 patients were admitted to the ICU and were evaluated. Most patients included in the studies were male (76 165/128 168, 59%, 26 studies) and the mean patient age was 56 (95%CI 48.5–59.8) years. Studies described high ICU mortality (21 145/65 383, 32.3%, 15 studies). The median length of ICU stay was 9.0 (95%CI 6.5–11.2) days, described in five studies. More than half the patients admitted to the ICU required mechanical ventilation (31 213/53 465, 58%, 23 studies) and among them mortality was very high (27 972/47 632, 59%, six studies). The duration of mechanical ventilation was 8.4 (95%CI 1.6–13.7) days. The main interventions described were the use of non-invasive ventilation, extracorporeal membrane oxygenation, renal replacement therapy and vasopressors.ConclusionsThis systematic review, including approximately 69 000 ICU patients, demonstrates that COVID-19 infection in critically ill patients is associated with great need for life-sustaining interventions, high mortality, and prolonged length of ICU stay.     

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis

ObjectivesCytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients.MethodsData sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I². We assessed the certainty of evidence using the GRADE approach.ResultsOf 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80–1.49, I² = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52–0.96, I² = 0%), with a corresponding number needed to treat of 17 (95%CI 9–100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51–0.66, I² = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38–1.06, five RCTs) and 0.83 (95%CI 0.55–1.24, five RCTs), respectively.ConclusionsCumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.     

Post–COVID-19 syndrome and humoral response association after 1 year in vaccinated and unvaccinated patients

ObjectivesThis study aimed to describe the impact of vaccination and the role of humoral responses on post–COVID-19 syndrome 1 year after the onset of SARS coronavirus type 2 (CoV-2).MethodsThis prospective study was conducted through interviews to investigate post–COVID-19 syndrome 6 and 12 months after disease onset in all adult in- and outpatients with COVID-19 at Udine Hospital (March–May 2020). Vaccination status and two different serological assays to distinguish between response to vaccination (receptor-binding domain (RBD) SARS-CoV-2 IgG) and/or natural infection (non-RBD-SARS-CoV-2 IgG) were also assessed.ResultsA total of 479 patients (52.6% female; mean age: 53 years) were interviewed 13.5 months (standard deviation: 0.6 months) after acute infection. Post–COVID-19 syndrome was observed in 47.2% of patients (n = 226) after 1 year. There were no significant differences in the worsening of post–COVID-19 symptoms (22.7% vs. 15.8%; p = 0.209) among vaccinated (n = 132) and unvaccinated (n = 347) patients. The presence of non-RBD SARS-CoV-2 IgG induced by natural infection showed a significant association with post–COVID-19 syndrome (OR: 1.35; 95% CI, 1.11–1.64; p = 0.003), and median non-RBD SARS-CoV-2 IgG titres were significantly higher in long haulers than in patients without symptoms (22 kAU/L (interquartile range, 9.7–37.2 kAU/L) vs. 14.1 kAU/L (interquartile range, 5.4–31.3 kAU/L); p = 0.009) after 1 year. In contrast, the presence of RBD SARS-CoV-2 IgG was not associated with the occurrence of post–COVID-19 syndrome (>2500 U/mL vs. 0.9–2500 U/mL; OR: 1.36; 95% CI, 0.62–3.00; p = 0.441), and RBD SARS-CoV-2 IgG titres were similar in long haulers as in patients without symptoms (50% values > 2500 U/mL vs. 55.6% values > 2500 U/mL; p = 0.451).DiscussionThe SARS-CoV-2 vaccination is not associated with the emergence of post–COVID-19 symptoms more than 1 year after acute infection. The persistence of high serological titre response induced by natural infection, but not vaccination, may play a role in long-haul COVID-19.     

Multicenter evaluation of four immunoassays for the performance of early diagnosis of COVID-19 and assessment of antibody responses of patients with pneumonia in Taiwan

Background/purposeOur study goals were to evaluate the diagnostic performance of four anti-SARS-CoV-2 antibodies tests and the differences in dynamic immune responses between COVID-19 patients with and without pneumonia.MethodsWe collected 184 serum samples from 70 consecutively qRT-PCR-confirmed COVID-19 patients at four participating hospitals from 23 January 2020 to 30 September 2020. COVID-19 pneumonia was defined as the presence of new pulmonary infiltration. Serum samples were grouped by the duration after symptom onset on a weekly basis for antibody testing and analysis. The four immunoassays: Beckman SARS-CoV-2 IgG/IgM (Beckman Test), Siemens (ADVIA Centaur®) SARS-CoV-2 Total (COV2T) (Siemens Test), SBC COVID-19 IgG ELISA (SBC Test) and EliA SARS-CoV-2-Sp1 IgG/IgM/IgA P2 Research (EliA Test) were used for detecting the SARS-CoV-2 specific antibodies.ResultsThe sensitivity of all tests reached 100% after 42 days of symptom onset. Siemens Test, the only test detecting total anti-SARS-CoV-2 antibodies, had the best performance in the early diagnosis of COVID-19 infection (day 0–7: 77%; day 8–14: 95%) compared to the other 3 serological tests. All tests showed 100% specificity except SBC Test (98%). COVID-19 patients with pneumonia had significantly higher testing signal values than patients without pneumonia (all p values < 0.05, except EliA IgM Test). However, Siemens Test and SBC Test had highest probability in early prediction of the presence of COVID-19 pneumonia.ConclusionChronological analysis of immune response among COVID-19 patients with different serological tests provides important information in the early diagnosis of SARS-CoV-2 infection and prediction of the risk of pneumonia after infection.     

Association between first language and SARS-CoV-2 infection rates,hospitalization, intensive care admissions and death in Finland: a population-based observational cohort study

ObjectivesMotivated by reports of increased risk of coronavirus disease 2019 (COVID-19) in ethnic minorities of high-income countries, we explored whether patients with a foreign first language are at an increased risk of COVID-19 infections, more serious presentations, or worse outcomes.MethodsIn a retrospective observational population-based quality registry study covering a population of 1.7 million, we studied the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), admissions to specialist healthcare and the intensive care unit (ICU), and all-cause case fatality in different language groups between 27th February and 3rd August 2020 in Southern Finland. A first language other than Finnish, Swedish or Sámi served as a surrogate marker for a foreign ethnic background.ResultsIn total, 124 240 individuals were tested, and among the 118 300 (95%) whose first language could be determined, 4005 (3.4%) were COVID-19-positive, 623 (0.5%) were admitted to specialized hospitals, and 147 (0.1%) were admitted to the ICU; 254 (0.2%) died. Those with a foreign first language had lower testing rates (348, 95%CI 340–355 versus 758, 95%CI 753–762 per 10 000, p < 0.0001), higher incidence (36, 95%CI 33–38 versus 22, 95%CI 21–23 per 10 000, p < 0.0001), and higher positivity rates (103, 95%CI 96–109 versus 29, 95%CI 28–30 per 1000, p < 0.0001). There was no significant difference in ICU admissions, disease severity at ICU admission, or ICU outcomes. Case fatality by 90 days was 7.7% in domestic cases and 1.2% in those with a foreign first language, explained by demographics (age- and sex-adjusted HR 0.49, 95%CI 0.21–1.15).ConclusionsThe population with a foreign first language was at an increased risk for testing positive for SARS-CoV-2, but when hospitalized they had outcomes similar to those in the native, domestic language population. This suggests that special attention should be paid to the prevention and control of infectious diseases among language minorities.     

Recommendations for antibacterial therapy in adults with COVID-19 – an evidence based guideline

ScopeThe Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19).MethodsWe performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology.Questions addressed by the guideline and RecommendationsWe assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.     

The association between antimicrobial resistance and HIV infection: a systematic review and meta-analysis

ObjectivesPeople living with HIV (PLWH) are at increased risk of infections with resistant organisms due to more frequent healthcare utilization. Our objective was to investigate the association between HIV and antimicrobial resistance (AMR).MethodsWe searched MEDLINE, EMBASE, Web of Science, LILACS and African Journals Online. Studies were eligible if they reported on AMR for colonization or infection with bacterial pathogens (excluding mycobacteria and bacteria causing sexually transmitted infections) and were stratified by HIV status, species and antimicrobials tested. Pooled odds ratios were used to evaluate the association between HIV and resistance.ResultsIn total, 92 studies published between 1995 and 2020 were identified. The studies included the following organisms: Staphylococcus aureus (n = 47), Streptococcus pneumoniae (n = 28), Escherichia coli (n = 6) and other Gram-negative bacteria. PLWH had a 2.12 (95%CI 1.36–3.30) higher odds for colonization and 1.90 (95%CI 1.45–2.48) higher odds for infection with methicillin-resistant S. aureus, a 2.28 (95%CI 1.75–2.97) higher odds of infection with S. pneumoniae with decreased penicillin susceptibility, and a 1.59 (95%CI 0.83-3.05) higher odds of resistance to third-generation cephalosporins in E. coli and Klebsiella pneumoniae.ConclusionThis review shows an increased risk of AMR in PLWH across a range of bacterial pathogens and multiple drug classes. The lack of laboratory capacity for identifying AMR, and limited access to alternative treatment options in countries with the highest burden of HIV, highlight the need for more research on AMR in PLWH. Overall, the quality of studies was moderate or low, which may impact the findings of this review.     

Changes in the Occurrence of Gastrointestinal Infections after COVID-19 in Korea

BackgroundAfter the global epidemic of coronavirus disease 2019 (COVID-19), lifestyle changes to curb the spread of COVID-19 (e.g., wearing a mask, hand washing, and social distancing) have also affected the outbreak of other infectious diseases. However, few studies have been conducted on whether the incidence of gastrointestinal infections has changed over the past year with COVID-19. In this study, we examined how the incidence of gastrointestinal infections has changed since COVID-19 outbreak through open data.MethodsWe summarized the data on the several viruses and bacteria that cause gastrointestinal infections from the open data of the Korea Disease Control and Prevention Agency for 3 years from March 2018 to February 2021 (from Spring 2018 to Winter 2020). Moreover, we confirmed three most common legal gastrointestinal infectious pathogens from March 2016.ResultsFrom March 2020, when the COVID-19 epidemic was in full swing and social distancing and personal hygiene management were heavily emphasized, the incidence of infection from each virus was drastically decreased. The reduction rates compared to the averages of the last 2 years were as follows: total viruses 31.9%, norovirus 40.2%, group A rotavirus 31.8%, enteric adenovirus 13.4%, astrovirus 7.0%, and sapovirus 12.2%. Among bacterial pathogens, the infection rates of Campylobacter and Clostridium perfringens did not decrease but rather increased in some periods when compared to the average of the last two years. The incidence of nontyphoidal Salmonella, Staphylococcus aureus, or enteropathogenic Escherichia coli somewhat decreased but not significantly compared to the previous two years.ConclusionThe incidence of infection from gastrointestinal viruses, which are mainly caused by the fecal-to-oral route and require direct contact among people, was significantly reduced, whereas the incidence of bacterial pathogens, which have food-mediated transmission as the main cause of infection, did not decrease significantly.     

Field evaluation of a rapid antigen test (Panbio™ COVID-19 Ag Rapid Test Device) for COVID-19 diagnosis in primary healthcare centres

ObjectivesTo our knowledge no previous study has assessed the performance of a rapid antigen diagnostic immunoassay (RAD) conducted at the point of care (POC). We evaluated the Panbio? COVID-19 Ag Rapid Test Device for diagnosis of coronavirus 2019 disease (COVID-19) in symptomatic patients (n = 412) attending primary healthcare centres.MethodsRAD was performed immediately after sampling following the manufacturer's instructions (reading at 15 min). RT-PCRs were carried out within 24 h of specimen collection. Samples displaying discordant results were processed for culture in Vero E6 cells. Presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cell cultures was confirmed by RT-PCR.ResultsOut of 412 patients, 43 (10.4%) tested positive by RT-PCR and RAD, and 358 (86.9%) tested negative by both methods; discordant results (RT-PCR+/RAD–) were obtained in 11 patients (2.7%). Overall specificity and sensitivity of rapid antigen detection (RAD) was 100% (95%CI 98.7–100%) and 79.6% (95%CI 67.0–88.8%), respectively, taking RT-PCR as the reference. Overall RAD negative predictive value for an estimated prevalence of 5% and 10% was 99% (95%CI 97.4–99.6%) and 97.9% (95%CI 95.9–98.9), respectively. SARS-CoV-2 could not be cultured from specimens yielding RT-PCR+/RAD– results (n = 11).ConclusionThe Panbio? COVID-19 Ag Rapid Test Device performed well as a POC test for early diagnosis of COVID-19 in primary healthcare centres. More crucially, the data suggested that patients with RT-PCR-proven COVID-19 testing negative by RAD are unlikely to be infectious.