Low incidence of severe bacterial infections in hospitalised patients with COVID-19: A population-based registry study.

BACKGROUND: Bacterial infections complicating COVID-19 are rare but present a challenging clinical entity. The aim of this study was to evaluate the incidence, aetiology and outcome of severe laboratory-verified bacterial infections in hospitalised patients with COVID-19. METHODS: All laboratory-confirmed patients with COVID-19 admitted to specialised healthcare hospitals in the Capital Province of Finland during the first wave of COVID-19 between 27 February and 21 June 2020 were retrospectively studied. We gathered the blood and respiratory tract culture reports of these patients and analysed their association with 90-day case-fatality using multivariable regression analysis. RESULTS: A severe bacterial infection was diagnosed in 40/585 (6.8%) patients with COVID-19. The range of bacteria was diverse, and the most common bacterial findings in respiratory samples were gram-negative, and in blood cultures gram-positive bacteria. Patients with severe bacterial infection had longer hospital stay (mean 31; SD 20 days) compared to patients without (mean 9; SD 9 days; p < 0.001). Case-fatality was higher with bacterial infection (15% vs 11%), but the difference was not statistically significant (OR 1.38 CI95% 0.56-3.41). CONCLUSIONS: Severe bacterial infection complicating COVID-19 was a rare occurrence in our cohort. Our results are in line with the current understanding that antibiotic treatment for hospitalised COVID-19 patients should only be reserved for situations where a bacterial infection is strongly suspected. The ever-evolving landscape of the pandemic and recent advances in immunomodulatory treatment of COVID-19 patients underline the need for continuous vigilance concerning the possibility and frequency of nosocomial bacterial infections.

Isolation precautions cause minor delays in diagnostics and treatment of non-COVID patients.

BACKGROUND: Isolation precautions are essential prevent spread of COVID-19 infection but may have a negative impact on inpatient care. The impact of these measures on non-COVID-19 patients remains largely unexplored. AIM: This study aimed to investigate diagnostic and treatment delays related to isolation precautions, the associated patient outcome, and the predisposing risk factors for delays. METHODS: This observational study was conducted in seven Helsinki region hospitals during the first wave of the COVID-19 pandemic in Finland. The study used data on all non-COVID-19 inpatients, who were initially isolated due to suspected COVID-19, to estimate whether isolation precautions resulted in diagnostic or treatment delays. RESULTS: Out of 683 non-COVID-19 patients, 33 (4.8%) had delays related to isolation precautions. Clinical condition deteriorated non-fatally in seven (1.0%) patients. The following events were associated with an increased risk of treatment or a diagnostic delay: more than three ward transfers (P = 0.025); referral to an incorrect speciality in the emergency department (P = 0.004); more than three SARS-CoV-2 RT-PCR tests performed (P = 0.022); and where cancer was the final diagnosis (P = 0.018). In contrast, lower respiratory tract symptoms (P = 0.013) decreased the risk. CONCLUSIONS: The use of isolation precautions for patients who did not have COVID-19 had minor negative effects on patient outcomes. The present study underlines the importance of targeting diagnostic efforts to patients with unspecified symptoms and to those with a negative SARS-CoV-2 test result. Thorough investigations to achieve an accurate diagnosis improves the prognosis of patients and facilitates appropriate targeting of hospital resources.

Detection of SARS-CoV-2 nucleocapsid antigen from serum can aid in timing of COVID-19 infection.

SARS-CoV-2 RNA can be detected in respiratory samples for weeks after onset of COVID-19 disease. Therefore, one of the diagnostic challenges of PCR positive cases is differentiating between acute COVID-19 disease and convalescent phase. The presence of SARS-CoV-2 nucleocapsid antigen in serum and plasma samples of COVID-19 patients has been demonstrated previously. Our study aimed to characterize the analytical specificity and sensitivity of an enzyme-linked immunosorbent assay (Salocor SARS-CoV-2 Antigen Quantitative Assay Kit© (Salofa Ltd, Salo, Finland)) for the detection of SARS-CoV-2 nucleocapsid antigen in serum, and to characterize the kinetics of antigenemia. The evaluation material included a negative serum panel of 155 samples, and 126 serum samples from patients with PCR-confirmed COVID-19. The specificity of the Salocor SARS-CoV-2 serum nucleocapsid antigen test was 98.0 %. In comparison with simultaneous positive PCR from upper respiratory tract (URT) specimens, the test sensitivity was 91.7 %. In a serum panel in which the earliest serum sample was collected two days before the collection of positive URT specimen, and the latest 48 days after (median 1 day post URT sample collection), the serum N antigen test sensitivity was 95.6 % within 14 days post onset of symptoms. The antigenemia resolved approximately two weeks after the onset of disease and diagnostic PCR. The combination of simultaneous SARS-CoV-2 antigen and antibody testing appeared to provide useful information for timing of COVID-19. Our results suggest that SARS-CoV-2 N-antigenemia may be used as a diagnostic marker in acute COVID-19.

Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

Evaluation of three rapid lateral flow antigen detection tests for the diagnosis of SARS-CoV-2 infection.

INTRODUCTION: The COVID-19 pandemic has led to high demand of diagnostic tools. Rapid antigen detection tests have been developed and many have received regulatory acceptance such as CE IVD or FDA markings. Their performance needs to be carefully assessed. MATERIALS AND METHODS: 158 positive and 40 negative retrospective samples collected in saline and analyzed by a laboratory-developed RT-PCR test were used to evaluate Sofia (Quidel), Standard Q (SD Biosensor), and Panbio™ (Abbott) rapid antigen detection tests (RADTs). A subset of the specimens was subjected to virus culture. RESULTS: The specificity of all RADTs was 100 % and the sensitivity and percent agreement was 80 % and 85 % for Sofia, 81 % and 85 % for Standard Q, and 83 % and 86 % for Panbio™, respectively. All three RADTs evaluated in this study reached a more than 90 % sensitivity for samples with a high viral load as estimated from the low Ct (Cycle threshold) values in the reference RT-PCR. Virus culture was successful in 80 % of specimens with a Ct value <25. CONCLUSIONS: As expected, the RADTs were less sensitive than RT-PCR. However, they benefit from the speed and ease of testing, and lower price as compared to RT-PCR. Repeated testing in appropriate settings may improve the overall performance.

Laboratory-based surveillance of COVID-19 in the Greater Helsinki area, Finland, February-June 2020.

OBJECTIVES: The aim was to characterise age- and sex-specific severe acute respiratory syndrome coronavirus disease-2 (SARS-CoV-2) RT-PCR sampling frequency and positivity rate in Greater Helsinki area in Finland during February-June 2020. We also describe the laboratory capacity building for these diagnostics. METHODS: Laboratory registry data for altogether 80,791 specimens from 70,517 individuals was analysed. The data included the date of sampling, sex, age and the SARS-CoV-2 RT-PCR test result on specimens collected between 1 February and 15 June 2020. RESULTS: Altogether, 4057/80,791 (5.0%) of the specimens were positive and 3915/70,517 (5.6%) of the individuals were found positive. In all, 37% of specimens were from male and 67% from female subjects. While the number of positive cases was similar in male and female subjects, the positivity rate was significantly higher in male subjects: 7.5% of male and 4.4% of female subjects tested positive. The highest incidence/100,000 was observed in those aged ≥80 years. The proportion of young adults in positive cases increased in late May 2020. Large dips in testing frequency were observed during every weekend and also during public holidays. CONCLUSIONS: Our data suggest that men pursue SARS-CoV-2 testing less frequently than women. Consequently, a subset of coronavirus disease-2019 infections in men may have gone undetected. People sought testing less frequently on weekends and public holidays, and this may also lead to missing of positive cases. The proportion of young adults in positive cases increased towards the end of the study period, which may suggest their returning back to social behaviour with an increased risk of infection.

Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation.

There is an urgent need for reliable high-throughput serological assays for the management of the ongoing COVID-19 pandemic. Preferably, the performance of serological tests for a novel virus should be determined with clinical specimens against a gold standard, i.e. virus neutralisation. We compared the performance of six commercial immunoassays for the detection of SARS-COV-2 IgG, IgA and IgM antibodies, including four automated assays [Abbott SARS-COV-2 IgG (CE marked), Diasorin Liaison® SARS-COV-2 S1/S2 IgG (research use only, RUO), and Euroimmun SARS-COV-2 IgG and IgA (CE marked)], and two rapid lateral flow (immunocromatographic) tests [Acro Biotech 2019-nCoV IgG/IgM (CE marked) and Xiamen Biotime Biotechnology SARS-COV-2 IgG/IgM (CE marked)] with a microneutralisation test (MNT). Two specimen panels from serum samples sent to Helsinki University Hospital Laboratory (HUSLAB) were compiled: the patient panel (N=70) included sera from PCR confirmed COVID-19 patients, and the negative panel (N=81) included sera sent for screening of autoimmune diseases and respiratory virus antibodies in 2018 and 2019. The MNT was carried out for all COVID-19 samples (70 serum samples, 62 individuals) and for 53 samples from the negative panel. Forty-one out of 62 COVID-19 patients showed neutralising antibodies.The specificity and sensitivity values of the commercial tests against MNT, respectively, were as follows: 95.1 %/80.5 % (Abbott Architect SARS-CoV-2 IgG), 94.9 %/43.8 % (Diasorin Liaison SARS-CoV-2 IgG; RUO), 68.3 %/87.8 % (Euroimmun SARS-CoV-2 IgA), 86.6 %/70.7 % (Euroimmun SARS-CoV-2 IgG), 74.4 %/56.1 % (Acro 2019-nCoV IgG), 69.5 %/46.3 % (Acro 2019-nCoV IgM), 97.5 %/71.9 % (Xiamen Biotime SARS-CoV-2 IgG), and 88.8 %/81.3 % (Xiamen Biotime SARS-CoV-2 IgM). This study shows variable performance values. Laboratories should carefully consider their testing process, such as a two-tier approach, in order to optimize the overall performance of SARS- CoV-2 serodiagnostics.