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1.
Front Immunol ; 13: 869990, 2022.
Article in English | MEDLINE | ID: covidwho-1834409

ABSTRACT

The emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made it more difficult to prevent the virus from spreading despite available vaccines. Reports of breakthrough infections and decreased capacity of antibodies to neutralize variants raise the question whether current vaccines can still protect against COVID-19 disease. We studied the dynamics and persistence of T cell responses using activation induced marker (AIM) assay and Th1 type cytokine production in peripheral blood mononuclear cells obtained from BNT162b2 COVID-19 mRNA vaccinated health care workers and COVID-19 patients. We demonstrate that equally high T cell responses following vaccination and infection persist at least for 6 months against Alpha, Beta, Gamma, and Delta variants despite the decline in antibody levels.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19 Vaccines , Humans , Leukocytes, Mononuclear , RNA, Messenger/genetics , Spike Glycoprotein, Coronavirus , T-Lymphocytes
2.
Nat Commun ; 13(1): 2476, 2022 May 05.
Article in English | MEDLINE | ID: covidwho-1821587

ABSTRACT

Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , Humans , SARS-CoV-2 , Vaccines, Synthetic
3.
Microbiol Spectr ; 10(2): e0225221, 2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1736039

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has raised concern about increased transmissibility, infectivity, and immune evasion from a vaccine and infection-induced immune responses. Although COVID-19 mRNA vaccines have proven to be highly effective against severe COVID-19 disease, the decrease in vaccine efficacy against emerged Beta and Delta variants emphasizes the need for constant monitoring of new virus lineages and studies on the persistence of vaccine-induced neutralizing antibodies. To analyze the dynamics of COVID-19 mRNA vaccine-induced antibody responses, we followed 52 health care workers in Finland for 6 months after receiving two doses of BNT162b2 vaccine with a 3-week interval. We demonstrate that, although anti-S1 antibody levels decrease 2.3-fold compared to peak antibody levels, anti-SARS-CoV-2 antibodies persist for months after BNT162b2 vaccination. Variants D614G, Alpha, and Eta are neutralized by sera of 100% of vaccinees, whereas neutralization of Delta is 3.8-fold reduced and neutralization of Beta is 5.8-fold reduced compared to D614G. Despite this reduction, 85% of sera collected 6 months postvaccination neutralizes Delta variant. IMPORTANCE A decrease in vaccine efficacy against emerging SARS-CoV-2 variants has increased the importance of assessing the persistence of SARS-CoV-2 spike protein-specific antibodies and neutralizing antibodies. Our data show that after 6 months post two doses of BNT162b2 vaccine, antibody levels decrease yet remain detectable and capable of neutralizing emerging variants. By monitoring the vaccine-induced antibody responses, vaccination strategies and administration of booster doses can be optimized.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Humans , RNA, Messenger , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Vaccination , Vaccines, Synthetic
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323393

ABSTRACT

SARS-CoV-2 infection raises neutralizing antibodies (NAbs). While studies have shown differing NAb kinetics, they generally point to the antibody arm of immunity providing most recoverees protection against contemporary strains. However, the effect against newly emerged variants of concern (VoCs) has remained uncertain. Here, applying neutralization tests to paired recoveree sera (N=38) of spring 2020 COVID-19 patients with clinical isolates of wildtype D614G and VoC1 and -2 strains (B.1.1.7 and B 1.351) from Finland, we show that NAbs of these patients are equally effective in inhibiting both contemporary and VoC1 strains whereas inhibition of VoC2 is reduced 8-fold (p<0.001) with 50% of sera failing to show NAbs. Our results align with an increased ability of VoC2 to reinfect previously SARS-CoV-infected populations.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313181

ABSTRACT

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees’ neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides strong evidence that the second dose of the BNT162b2 vaccine induces efficient cross-neutralization of SARS-CoV-2 variants currently circulating in the world.

6.
Acta Neuropathol Commun ; 9(1): 199, 2021 12 23.
Article in English | MEDLINE | ID: covidwho-1634344

ABSTRACT

Apolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.


Subject(s)
Apolipoprotein E4/genetics , COVID-19/complications , COVID-19/genetics , Cerebral Hemorrhage/genetics , Mental Fatigue/genetics , Patient Acuity , Adult , Aged , Autopsy , Biological Specimen Banks , COVID-19/diagnosis , COVID-19/epidemiology , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/epidemiology , Cohort Studies , Female , Finland/epidemiology , Genetic Association Studies/methods , Heterozygote , Humans , Male , Mental Fatigue/diagnosis , Mental Fatigue/epidemiology , Microvessels/pathology , Middle Aged , Prospective Studies , Risk Factors , Young Adult
7.
Viruses ; 13(12)2021 12 11.
Article in English | MEDLINE | ID: covidwho-1572663

ABSTRACT

BACKGROUND: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. METHODS: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. RESULTS: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFNα, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFNα-remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFNα combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies. CONCLUSIONS: Altogether, our results indicated that IFNα can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections.


Subject(s)
Antiviral Agents/pharmacology , Interferon-alpha/pharmacology , SARS-CoV-2/drug effects , Cell Line , Drug Synergism , Humans , Lung/drug effects , Lung/metabolism , Lung/virology , Metabolome/drug effects , Organoids , RNA, Viral/biosynthesis , RNA, Viral/drug effects , Signal Transduction/drug effects , Transcriptome/drug effects , Virus Replication/drug effects , Viruses/classification , Viruses/drug effects
8.
Microbiol Spectr ; 9(3): e0113121, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1522926

ABSTRACT

Validation and standardization of accurate serological assays are crucial for the surveillance of the coronavirus disease 2019 (COVID-19) pandemic and population immunity. We describe the analytical and clinical performance of an in-house fluorescent multiplex immunoassay (FMIA) for simultaneous quantification of antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein and spike glycoprotein. Furthermore, we calibrated IgG-FMIA against World Health Organization (WHO) International Standard and compared FMIA results to an in-house enzyme immunoassay (EIA) and a microneutralization test (MNT). We also compared the MNT results of two laboratories. IgG-FMIA displayed 100% specificity and sensitivity for samples collected 13 to 150 days post-onset of symptoms (DPO). For IgA- and IgM-FMIA, 100% specificity and sensitivity were obtained for a shorter time window (13 to 36 and 13 to 28 DPO for IgA- and IgM-FMIA, respectively). FMIA and EIA results displayed moderate to strong correlation, but FMIA was overall more specific and sensitive. IgG-FMIA identified 100% of samples with neutralizing antibodies (NAbs). Anti-spike IgG concentrations correlated strongly (ρ = 0.77 to 0.84, P < 2.2 × 10-16) with NAb titers, and the two laboratories' NAb titers displayed a very strong correlation (ρ = 0.95, P < 2.2 × 10-16). Our results indicate good correlation and concordance of antibody concentrations measured with different types of in-house SARS-CoV-2 antibody assays. Calibration against the WHO international standard did not, however, improve the comparability of FMIA and EIA results. IMPORTANCE SARS-CoV-2 serological assays with excellent clinical performance are essential for reliable estimation of the persistence of immunity after infection or vaccination. In this paper we present a thoroughly validated SARS-CoV-2 serological assay with excellent clinical performance and good comparability to neutralizing antibody titers. Neutralization tests are still considered the gold standard for SARS-CoV-2 serological assays, but our assay can identify samples with neutralizing antibodies with 100% sensitivity and 96% specificity without the need for laborious and slow biosafety level 3 (BSL-3) facility-requiring analyses.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Serological Testing/methods , Fluorescent Antibody Technique/methods , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Nucleocapsid Proteins/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Neutralizing/immunology , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/immunology , Humans , Nucleoproteins , Phosphoproteins/immunology , SARS-CoV-2 , Sensitivity and Specificity
9.
Thromb Res ; 208: 129-137, 2021 12.
Article in English | MEDLINE | ID: covidwho-1500293

ABSTRACT

BACKGROUND: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare coagulation disorder reported after administration of COVID-19 adenovirus-vectored vaccines. VITT is mediated by anti-platelet factor 4 (PF4) antibodies activating platelets through the Fcγ-receptor II (FcγRII), and it is associated with strong fibrin turnover. The complement system is involved in several other immunothrombotic entities, but its impact on VITT is not established. OBJECTIVE: To assess antibodies in interaction with the activation of platelets and complement triggered by VITT. METHODS: Antibodies against adenovirus type 2 hexon protein, ChAdOx1 adenoviral vector-specific IgG and PF4 were analyzed by enzyme immunoassays from VITT patients (n = 5). The EDTA plasma samples of the patients and controls were used to measure both terminal complement complexes (TCC) by ELISA and aggregation of healthy donor platelets. We studied the effects of human immunoglobulin (IVIG) and glycoprotein IIb/IIIa inhibitor (GPIIb/IIIa) on spontaneous and collagen-induced platelet aggregation supplemented with VITT plasma. RESULTS: None of the patients had experienced a COVID-19 infection. Antibody analyses confirmed the immunogenicity of the adenovirus-vectored ChAdOx1 vaccine. Moreover, VITT plasma had anti-PF4 antibodies and elevated TCC levels as a sign of complement activation. In isolated healthy donor platelets, VITT patient plasma caused marked, spontaneous aggregation of platelets, which was abolished by eptifibatide and high-dose therapeutic IVIG. CONCLUSIONS: Our findings suggest that VITT is triggered by antibodies against adenovirus vector and PF4-polyanion complexes which strongly co-activate complement and platelets. The spontaneous platelet aggregation was suppressed by IVIG or eptifibatide, indicating that besides FcγRII, also GPIIb/IIIa receptor exerts platelet procoagulant role in VITT.


Subject(s)
Adenovirus Vaccines , COVID-19 , Adenoviridae , Blood Platelets , COVID-19 Vaccines , Humans , Immunoglobulin G , Platelet Factor 4 , SARS-CoV-2
10.
Clin Microbiol Infect ; 28(1): 107-113, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1446536

ABSTRACT

OBJECTIVES: Motivated 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. METHODS: In 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. RESULTS: In 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). CONCLUSIONS: The 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.


Subject(s)
COVID-19 , /statistics & numerical data , COVID-19/epidemiology , COVID-19/ethnology , Cohort Studies , Critical Care , Finland/epidemiology , Hospitalization , Humans , Intensive Care Units , Language , Retrospective Studies
11.
PLoS Pathog ; 17(7): e1009721, 2021 07.
Article in English | MEDLINE | ID: covidwho-1298084

ABSTRACT

Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression.


Subject(s)
COVID-19/immunology , Granulocytes/classification , Acute Disease , Adult , Aged , COVID-19/blood , Case-Control Studies , Cohort Studies , Convalescence , Disease Progression , Female , Follow-Up Studies , Granulocytes/cytology , Humans , Immune Tolerance/immunology , Male , Middle Aged , Scavenger Receptors, Class E/analysis , Severity of Illness Index
12.
Nat Commun ; 12(1): 3991, 2021 06 28.
Article in English | MEDLINE | ID: covidwho-1286457

ABSTRACT

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees' neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants.


Subject(s)
Broadly Neutralizing Antibodies/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , COVID-19/blood , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , Cross Protection/immunology , Female , Finland/epidemiology , Humans , Immunization, Secondary/methods , Immunization, Secondary/statistics & numerical data , Male , Mass Vaccination/methods , Mass Vaccination/statistics & numerical data , Middle Aged , Neutralization Tests/statistics & numerical data , Reinfection/immunology , Reinfection/prevention & control , Reinfection/virology , SARS-CoV-2/genetics , Young Adult
13.
Viruses ; 13(6)2021 05 26.
Article in English | MEDLINE | ID: covidwho-1244152

ABSTRACT

Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera (n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/virology , Chlorocebus aethiops , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immunoglobulin G/immunology , Kinetics , Neutralization Tests , Phosphoproteins/immunology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
14.
Front Med (Lausanne) ; 7: 607786, 2020.
Article in English | MEDLINE | ID: covidwho-1069727

ABSTRACT

Background: Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. Methods: We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Findings: Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988, p < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773-0.944, p = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Interpretation: Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.

15.
Viruses ; 13(2)2021 Jan 20.
Article in English | MEDLINE | ID: covidwho-1067779

ABSTRACT

Accurate and rapid diagnostic tools are needed for management of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Antibody tests enable detection of individuals past the initial phase of infection and help examine vaccine responses. The major targets of human antibody response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the spike glycoprotein (SP) and nucleocapsid protein (NP). We have developed a rapid homogenous approach for antibody detection termed LFRET (protein L-based time-resolved Förster resonance energy transfer immunoassay). In LFRET, fluorophore-labeled protein L and antigen are brought to close proximity by antigen-specific patient immunoglobulins of any isotype, resulting in TR-FRET signal. We set up LFRET assays for antibodies against SP and NP and evaluated their diagnostic performance using a panel of 77 serum/plasma samples from 44 individuals with COVID-19 and 52 negative controls. Moreover, using a previously described SP and a novel NP construct, we set up enzyme linked immunosorbent assays (ELISAs) for antibodies against SARS-CoV-2 SP and NP. We then compared the LFRET assays with these ELISAs and with a SARS-CoV-2 microneutralization test (MNT). We found the LFRET assays to parallel ELISAs in sensitivity (90-95% vs. 90-100%) and specificity (100% vs. 94-100%). In identifying individuals with or without a detectable neutralizing antibody response, LFRET outperformed ELISA in specificity (91-96% vs. 82-87%), while demonstrating an equal sensitivity (98%). In conclusion, this study demonstrates the applicability of LFRET, a 10-min "mix and read" assay, to detection of SARS-CoV-2 antibodies.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/diagnosis , Immunoassay/methods , SARS-CoV-2/isolation & purification , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , Coronavirus Nucleocapsid Proteins/immunology , Humans , Phosphoproteins/immunology , SARS-CoV-2/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology
16.
Travel Med Infect Dis ; 39: 101949, 2021.
Article in English | MEDLINE | ID: covidwho-970990

ABSTRACT

BACKGROUND: Exposure, risks and immunity of healthcare workers (HCWs), a vital resource during the SARS-CoV-2 pandemic, warrant special attention. METHODS: HCWs at Helsinki University Hospital, Finland, filled in questionnaires and provided serum samples for SARS-CoV-2-specific antibody screening by Euroimmun IgG assay in March-April 2020. Positive/equivocal findings were confirmed by Abbott and microneutralization tests. Positivity by two of the three assays or RT-PCR indicated a Covid-19 case (CoV+). RESULTS: The rate of CoV(+) was 3.3% (36/1095) and seropositivity 3.0% (33/1095). CoV(+) was associated with contact with a known Covid-19 case, and working on a Covid-19-dedicated ward or one with cases among staff. The rate in the Covid-19-dedicated ICU was negligible. Smoking and age <55 years were associated with decreased risk. CoV(+) was strongly associated with ageusia, anosmia, myalgia, fatigue, fever, and chest pressure. Seropositivity was recorded for 89.3% of those with prior documented RT-PCR-positivity and 2.4% of those RT-PCR-negative. The rate of previously unidentified cases was 0.7% (8/1067) and asymptomatic ones 0% (0/36). CONCLUSION: Undiagnosed and asymptomatic cases among HCWs proved rare. An increased risk was associated with Covid-19-dedicated wards. Particularly high rates were seen for wards with liberal HCW-HCW contacts, highlighting the importance of social distancing also among HCWs.


Subject(s)
COVID-19/epidemiology , Health Personnel/statistics & numerical data , SARS-CoV-2/immunology , Adult , Antibodies, Viral/blood , Asymptomatic Infections/epidemiology , COVID-19/diagnosis , COVID-19/pathology , COVID-19/prevention & control , Female , Finland/epidemiology , Hospitals, University , Humans , Male , Middle Aged , Risk Factors , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies
18.
Cell Rep Med ; 1(5): 100078, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-694586

ABSTRACT

Severe disease of SARS-CoV-2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses are required to capture cellular interactions. Here, we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ-eosinophil axis activated before lung hyperinflammation and changes in cell-cell co-regulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.


Subject(s)
COVID-19/immunology , Adaptive Immunity , Adult , Basophils/metabolism , COVID-19/blood , Cell Communication , Convalescence , Eosinophils/metabolism , Female , Humans , Inflammation , Interferon-gamma/blood , Interleukin-6/blood , Longitudinal Studies , Male , SARS-CoV-2 , Severity of Illness Index
19.
Euro Surveill ; 25(11)2020 03.
Article in English | MEDLINE | ID: covidwho-18570

ABSTRACT

The first case of coronavirus disease (COVID-19) in Finland was confirmed on 29 January 2020. No secondary cases were detected. We describe the clinical picture and laboratory findings 3-23 days since the first symptoms. The SARS-CoV-2/Finland/1/2020 virus strain was isolated, the genome showing a single nucleotide substitution to the reference strain from Wuhan. Neutralising antibody response appeared within 9 days along with specific IgM and IgG response, targeting particularly nucleocapsid and spike proteins.


Subject(s)
Contact Tracing , Coronavirus Infections , Coronavirus/genetics , Coronavirus/isolation & purification , Pandemics , Pneumonia, Viral , SARS Virus/immunology , Severe Acute Respiratory Syndrome/immunology , Travel , Adult , Antibodies, Viral/blood , Asymptomatic Infections , Betacoronavirus , COVID-19 , COVID-19 Testing , China , Clinical Laboratory Techniques , Coronavirus/immunology , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , Finland , Fluorescent Antibody Technique , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Neutralization Tests , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/etiology , Severe Acute Respiratory Syndrome/virology , Viral Envelope Proteins
20.
Int J Infect Dis ; 93: 268-276, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-1172

ABSTRACT

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of the general population from emerging and re-emerging viral diseases, reinforcing the arsenal of available antiviral options. Here, we review discovery and development of BSAAs and summarize the information on 120 safe-in-man agents in a freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand the spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.


Subject(s)
Antiviral Agents , Drug Development , Drug Discovery , Animals , Antiviral Agents/therapeutic use , Humans , Virus Diseases/drug therapy
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