Significance of mucosal associated invariant T (MAIT) Cells in SARS-CoV-2 infection

In the COVID-19 disease caused by SARS-CoV-2 virus prolonged T cell lymphopenia is common but the mechanism for it is still unknown. More importantly, the T cell lymphopenia is associated with more severe diseases. The lymphopenia in COVID-19 is more pronounced in a specialized innate-like T cell population called Mucosal Associated Invariant T cells (MAITs). MAITs are the only T cell population that expresses ACE2 receptor that SARS-CoV-2 uses for cell entry. This project aims to decipher the pathogenetic process leading to MAITs depletion in COVID-19. We hypothesize that SARS-CoV-2 can directly activate MAITs which leads to MAITs overactivation and excessive tissue destruction in the lungs where MAITs comprise a large part of the tissue-resident T cells. To test these hypotheses, we challenged MAITs isolated from healthy blood donors and controls from different age groups with SARS-CoV-2 in vitro in a BSL3 laboratory. We used a combination of multi-colour flow cytometry, RT-PCR and in situ lung immunohistochemistry to evaluate the changes in MAIT cells' functions and activation. We then translated the in vitro findings to in vivo and measured similar MAIT cell activation signatures from actual real-life patient samples obtained during acute COVID-19. Our study shows that human circulation MAIT cells are activated and declined in patients with SARS-CoV-2 infection. SARS-CoV-2 infects MAIT cells in a non-direct way.

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.

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.