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1.
Viruses ; 14(5):1075, 2022.
Article in English | MDPI | ID: covidwho-1857137

ABSTRACT

The role of environmental transmission of SARS-CoV-2 remains unclear. Thus, the aim of this study was to investigate whether viral contamination of air, wastewater, and surfaces in quarantined households result in a higher risk for exposed persons. For this study, a source population of 21 households under quarantine conditions with at least one person who tested positive for SARS-CoV-2 RNA were randomly selected from a community in North Rhine-Westphalia in March 2020. All individuals living in these households participated in this study and provided throat swabs for analysis. Air and wastewater samples and surface swabs were obtained from each household and analysed using qRT-PCR. Positive swabs were further cultured to analyse for viral infectivity. Out of all the 43 tested adults, 26 (60.47%) tested positive using qRT-PCR. All 15 air samples were qRT-PCR-negative. In total, 10 out of 66 wastewater samples were positive for SARS-CoV-2 (15.15%) and 4 out of 119 surface samples (3.36%). No statistically significant correlation between qRT-PCR-positive environmental samples and the extent of the spread of infection between household members was observed. No infectious virus could be propagated under cell culture conditions. Taken together, our study demonstrates a low likelihood of transmission via surfaces. However, to definitively assess the importance of hygienic behavioural measures in the reduction of SARS-CoV-2 transmission, larger studies should be designed to determine the proportionate contribution of smear vs. droplet transmission.

2.
Computational and structural biotechnology journal ; 2022.
Article in English | EuropePMC | ID: covidwho-1837468

ABSTRACT

Graphical The first major COVID-19 outbreak in Germany occurred in Heinsberg in February 2020 with 388 officially reported cases. Unexpectedly, the first outbreak happened in a small town with little to no travelers. We used phylogenetic analyses to investigate the origin and spread of the virus in this outbreak. We sequenced 90 (23%) SARS-CoV-2 genomes from the 388 reported cases including the samples from the first documented cases. Phylogenetic analyses of these sequences revealed mainly two circulating strains with 74 samples assigned to lineage B.3 and 6 samples assigned to lineage B.1. Lineage B.3 was introduced first and probably caused the initial spread. Using phylogenetic analysis tools, we were able to identify closely related strains in France and hypothesized the possible introduction from France.

3.
Immunology ; 166(3): 327-340, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1784665

ABSTRACT

Age is associated with changes in the immune system which increase the risk for severe COVID-19. Here, we investigate SARS-CoV-2-reactive CD4 T cells from individuals recovered from SARS-CoV-2 infection with mild COVID-19 symptoms after 3, 6 and 9 months using incubation with SARS-CoV-2 S1, S2 and N-peptide pools, followed by flow cytometry for a Th1-activation profile or proliferation analyses. We found that SARS-CoV-2-reactive CD4 T cells are decreasing on average after 9 months but highly polyfunctional CD4 T cells can peak after 6-month recovery. We show that individuals older than 60 years of age have significantly more SARS-CoV-2-reactive T cells in their blood after 3 months of recovery compared to younger individuals and that the percentage of SARS-CoV-2-reactive Th1-directed CD4 T cells in the blood of mild-COVID-19-recovered individuals correlates with age. Finally, we show that individuals over the age of 40 have significantly increased the amounts of highly polyfunctional SARS-CoV-2-S-peptide-reactive CD4 T cells, compared to SARS-CoV-2 naïve individuals, than those under the age of 40. These findings suggest that in individuals recovered from mild COVID-19, increased age is associated with significantly more highly polyfunctional SARS-CoV-2-reactive CD4 T cells with a Th1-profile and that these responses persist over time.


Subject(s)
COVID-19 , SARS-CoV-2 , CD4-Positive T-Lymphocytes , Humans , Infant , Spike Glycoprotein, Coronavirus
4.
BMJ Open ; 12(4): e059809, 2022 04 06.
Article in English | MEDLINE | ID: covidwho-1779383

ABSTRACT

OBJECTIVES: The first German SARS-CoV-2 outbreak was a superspreading event in Gangelt, North Rhine-Westphalia, during indoor carnival festivities called 'Kappensitzung' (15 February 2020). We determined SARS-CoV-2 RT-PCR positivity rate, SARS-CoV-2-specific antibodies, and analysed the conditions and dynamics of superspreading, including ventilation, setting dimensions, distance from infected persons and behavioural patterns. DESIGN: In a cross-sectional epidemiological study (51 days postevent), participants were asked to give blood, pharyngeal swabs and complete self-administered questionnaires. SETTING: The SARS-CoV-2 superspreading event took place during festivities in the small community of Gangelt in February 2020. This 5-hour event included 450 people (6-79 years of age) in a building of 27 m × 13.20 m × 4.20 m. PARTICIPANTS: Out of 450 event participants, 411 volunteered to participate in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: infection status (determined by IgG ELISA). SECONDARY OUTCOME: symptoms (determined by questionnaire). RESULTS: Overall, 46% (n=186/404) of participants had been infected, and their spatial distribution was associated with proximity to the ventilation system (OR 1.39, 95% CI 0.86 to 2.25). Risk of infection was highly associated with age: children (OR 0.33, 95% CI 0.267 to 0.414) and young adults (age 18-25 years) had a lower risk of infection than older participants (average risk increase of 28% per 10 years). Behavioural differences were also risk associated including time spent outside (OR 0.55, (95% CI 0.33 to 0.91) or smoking (OR 0.32, 95% CI 0.124 to 0.81). CONCLUSIONS: Our findings underline the importance of proper indoor ventilation for future events. Lower susceptibility of children/young adults indicates their limited involvement in superspreading.


Subject(s)
COVID-19 , SARS-CoV-2 , Adolescent , Adult , Antibodies, Viral , COVID-19/epidemiology , Child , Cross-Sectional Studies , Disease Outbreaks , Germany/epidemiology , Humans , Infant , Young Adult
5.
ChemMedChem ; 17(5):e202200088, 2022.
Article in English | Wiley | ID: covidwho-1729113

ABSTRACT

The Front Cover illustrates the natural product andrographolide, which modulates the abundance of the transcription factor NRF2, a substrate of the E3 ligase KEAP1. Previous studies identified that this drug possessed anti-SARS-CoV-2 activity, but the mechanism of action remained unclear. The authors designed and synthesized novel andrographolide derivatives with a functional site to fine-tune physicochemical properties and for linker attachment. The team assayed this new set of compounds in a cell-based NRF2 reporter gene assay and determined their ability to decrease infectivity of virus-treated Vero-E6 cells. Data showed that NRF2 activation by compounds and inhibition of SARS-CoV-2 replication correlated well. The study opens new avenues to investigate natural products that target the KEAP1/NRF2 axis as anti-SARS-CoV-2 agents. More information can be found in the Research Article by Christian Steinebach et al. 

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320959

ABSTRACT

Smoking has been described as a risk factor for severe COVID-19. While there is clear evidence that smoking depresses pulmonary immune function and increases the risk for respiratory infectious diseases with severe complications, recent data suggest that it also may have a protective effect from SARS-CoV-2 infection. We therefore investigated the independent impact of smoking on SARS-CoV-2 infection in two separate studies including a representative cohort study (N=988) and a COVID-19 cluster-outbreak (N=404). Cigarette consumption of >=10 cigarettes/day we observed a reduced risk of SARS-CoV-2-infection (fully adjusted OR 0.424 (95% confidence interval 0.253- 0.712).Trial Registration Number: German Clinical Trials Register (https://www.drks.de, ID: DRKS00021306)Funding: Both cohort studies were funded by the Ministry of Labor, Health, and Social Affairs ofthe State of North Rhine-Westphalia, Germany.Conflict of Interest: All authors declare no conflicts of interest.Ethical Approval: The study was approved by the ethics committee of the medical faculty of University Bonn (approval number 085/20).

7.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327175

ABSTRACT

There is ongoing debate on the COVID-19 infection fatality rate (IFR) and the impact of COVID-19 on overall population mortality. Here, we addressed these issues in a community in Germany with a major superspreader event analyzing deaths over time as well as auditing death certificates in the community.18 deaths that occurred within the first 6 months of the pandemic in the community had a positive test for SARS-CoV-2. Six out of 18 SARS-CoV-2+ deaths had non-COVID-19 related causes of death (COD). Individuals with confirmed infection and COVID-19 COD typically died of respiratory failure (75%) and tended to have fewer reported comorbidities (p=0.029). Duration between first confirmed infection and death was negatively associated to COVID-19 being COD (p=0.04). Repeated seroprevalence essays on an original sample of 587 individuals in three visits showed modest increases in seroprevalence over time, and substantial seroreversion (30% [27/90] (95% CI: [20.5%;39.5%])). IFR estimates accordingly varied depending on COVID-19 death attribution and seroprevalence caveats. Careful ascertainment and audit of COVID-19 deaths are important in understanding the impact of the pandemic.

8.
ChemMedChem ; 17(5): e202100732, 2022 03 04.
Article in English | MEDLINE | ID: covidwho-1661603

ABSTRACT

Naturally occurring compounds represent a vast pool of pharmacologically active entities. One of such compounds is andrographolide, which is endowed with many beneficial properties, including the activity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). To initiate a drug repurposing or hit optimization campaign, it is imperative to unravel the primary mechanism(s) of the antiviral action of andrographolide. Here, we showed by means of a reporter gene assay that andrographolide exerts its anti-SARS-CoV-2 effects by inhibiting the interaction between Kelch-like ECH-associated protein 1 (KEAP1) and nuclear factor erythroid 2-related factor 2 (NRF2) causing NRF2 upregulation. Moreover, we demonstrated that subtle structural modifications of andrographolide could lead to derivatives with stronger on-target activities and improved physicochemical properties. Our results indicate that further optimization of this structural class is warranted to develop novel COVID-19 therapies.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Diterpenes/chemistry , SARS-CoV-2/drug effects , Animals , COVID-19/drug therapy , COVID-19/virology , Cell Line , Chlorocebus aethiops , Humans , Kelch-Like ECH-Associated Protein 1/metabolism , Molecular Docking Simulation , Molecular Structure , NF-E2-Related Factor 2/metabolism , SARS-CoV-2/physiology , Vero Cells , Virus Replication
9.
mBio ; : e0214121, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1650754

ABSTRACT

As public health guidelines throughout the world have relaxed in response to vaccination campaigns against SARS-CoV-2, it is likely that SARS-CoV-2 will remain endemic, fueled by the rise of more infectious SARS-CoV-2 variants. Moreover, in the setting of waning natural and vaccine immunity, reinfections have emerged across the globe, even among previously infected and vaccinated individuals. As such, the ability to detect reexposure to and reinfection by SARS-CoV-2 is a key component for global protection against this virus and, more importantly, against the potential emergence of vaccine escape mutations. Accordingly, there is a strong and continued need for the development and deployment of simple methods to detect emerging hot spots of reinfection to inform targeted pandemic response and containment, including targeted and specific deployment of vaccine booster campaigns. In this study, we identify simple, rapid immune biomarkers of reinfection in rhesus macaques, including IgG3 antibody levels against nucleocapsid and FcγR2A receptor binding activity of anti-RBD antibodies, that are recapitulated in human reinfection cases. As such, this cross-species analysis underscores the potential utility of simple antibody titers and function as price-effective and scalable markers of reinfection to provide increased resolution and resilience against new outbreaks. IMPORTANCE As public health and social distancing guidelines loosen in the setting of waning global natural and vaccine immunity, a deeper understanding of the immunological response to reexposure and reinfection to this highly contagious pathogen is necessary to maintain public health. Viral sequencing analysis provides a robust but unrealistic means to monitor reinfection globally. The identification of scalable pathogen-specific biomarkers of reexposure and reinfection, however, could significantly accelerate our capacity to monitor the spread of the virus through naive and experienced hosts, providing key insights into mechanisms of disease attenuation. Using a nonhuman primate model of controlled SARS-CoV-2 reexposure, we deeply probed the humoral immune response following rechallenge with various doses of viral inocula. We identified virus-specific humoral biomarkers of reinfection, with significant increases in antibody titer and function upon rechallenge across a range of humoral features, including IgG1 to the receptor binding domain of the spike protein of SARS-CoV-2 (RBD), IgG3 to the nucleocapsid protein (N), and FcγR2A receptor binding to anti-RBD antibodies. These features not only differentiated primary infection from reexposure and reinfection in monkeys but also were recapitulated in a sequencing-confirmed reinfection patient and in a cohort of putatively reinfected humans that evolved a PCR-positive test in spite of preexisting seropositivity. As such, this cross-species analysis using a controlled primate model and human cohorts reveals increases in antibody titers as promising cross-validated serological markers of reinfection and reexposure.

11.
J Med Virol ; 94(1): 388-392, 2022 01.
Article in English | MEDLINE | ID: covidwho-1366254

ABSTRACT

In the current COVID-19 pandemic, a better understanding of the relationship between merely binding and functionally neutralizing antibodies is necessary to characterize protective antiviral immunity following infection or vaccination. This study analyzes the level of correlation between the novel quantitative EUROIMMUN Anti-SARS-CoV-2 QuantiVac ELISA (IgG) and a microneutralization assay. A panel of 123 plasma samples from a COVID-19 outbreak study population, preselected by semiquantitative anti-SARS-CoV-2 IgG testing, was used to assess the relationship between the novel quantitative ELISA (IgG) and a microneutralization assay. Binding IgG targeting the S1 antigen was detected in 106 (86.2%) samples using the QuantiVac ELISA, while 89 (72.4%) samples showed neutralizing antibody activity. Spearman's correlation analysis demonstrated a strong positive relationship between anti-S1 IgG levels and neutralizing antibody titers (rs = 0.819, p < 0.0001). High and low anti-S1 IgG levels were associated with a positive predictive value of 72.0% for high-titer neutralizing antibodies and a negative predictive value of 90.8% for low-titer neutralizing antibodies, respectively. These results substantiate the implementation of the QuantiVac ELISA to assess protective immunity following infection or vaccination.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/immunology , COVID-19/pathology , COVID-19 Serological Testing/methods , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Neutralization Tests/methods , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology , Young Adult
12.
Front Med (Lausanne) ; 8: 704719, 2021.
Article in English | MEDLINE | ID: covidwho-1348513

ABSTRACT

We present a case of SARS-CoV-2 B.1. 525 infection in a healthcare worker despite the presence of highly neutralizing, multivariant-specific antibodies 7 weeks after full vaccination with the mRNA vaccine BNT162b2. We show that the virus replicated to high levels in the upper respiratory tract over the course of several days in the presence of strong antibody responses. The virus was readily propagatable in vitro, demonstrating the potential to transmit to others, bolstered by the fact that several household members were equally infected. This highlights the importance of protective measures even in vaccinated individuals.

13.
Cell Rep ; 35(13): 109320, 2021 06 29.
Article in English | MEDLINE | ID: covidwho-1275189

ABSTRACT

Memory B cells seem to be more durable than antibodies and thus crucial for the long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here we investigate SARS-CoV-2 spike-specific memory B cells and their dependence on CD4+ T cell help in different settings of coronavirus disease 2019 (COVID-19). Compared with severely ill individuals, those who recovered from mild COVID-19 develop fewer but functionally superior spike-specific memory B cells. Generation and affinity maturation of these cells is best associated with IL-21+CD4+ T cells in recovered individuals and CD40L+CD4+ T cells in severely ill individuals. The increased activation and exhaustion of memory B cells observed during COVID-19 correlates with CD4+ T cell functions. Intriguingly, CD4+ T cells recognizing membrane protein show a stronger association with spike-specific memory B cells than those recognizing spike or nucleocapsid proteins. Overall, we identify CD4+ T cell subsets associated with the generation of B cell memory during SARS-CoV-2 infection.


Subject(s)
B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/immunology , CD40 Ligand/immunology , CD40 Ligand/metabolism , Cross Reactions , Humans , Immunologic Memory , Interleukins/immunology , Interleukins/metabolism
14.
Infection ; 49(5): 1039-1043, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1274987

ABSTRACT

INTRODUCTION: The CoSHeP study provides novel data on SARS-CoV-2 seroconversion rates in healthcare professionals (HP) at risk at the University Hospital Bonn, a maximum healthcare provider in a region of 900.000 inhabitants. METHODS: Single-center, longitudinal observational study investigating rate of SARS-CoV-2 IgG seroconversion in HP at 2 time-points. SARS-CoV-2 IgG was measured with Roche Elecsys Anti-SARS-CoV-2 assay. RESULTS: Overall, 150 HP were included. Median age was 35 (range: 19-68). Main operational areas were intensive care unit (53%, n = 80), emergency room (31%, n = 46), and infectious disease department (16%, n = 24). SARS-CoV-2-IgG was detected in 5 participants (3%) at inclusion in May/June 2020, and in another 11 participants at follow-up (December 2020/ January 2021). Of the 16 seropositive participants, 14 had already known their SARS-CoV-2 infection because they had performed a PCR-test previously triggered by symptoms. Trailing chains of infection by self-assessment, 31% (n = 5) of infections were acquired through private contacts, 25% (n = 4) most likely through semi-private contacts during work. 13% (n = 2) were assumed to result through contact with contagious patients, further trailing was unsuccessful in 31% (n = 5). All five participants positive for SARS-CoV-2 IgG at inclusion remained positive with a median of 7 months after infection. DISCUSSION: Frontline HP caring for hospitalized patients with COVID-19 are at higher risk of SARS-CoV-2 infections. Noteworthy, based upon identified chains of infection most of the infections were acquired in private environment and semi-private contacts during work. The low rate of infection through infectious patients reveals that professional hygiene standards are effective in preventing SARS-CoV-2 infections in HP. Persisting SARS-CoV-2-IgG might indicate longer lasting immunity supporting prioritization of negative HP for vaccination.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Viral , Delivery of Health Care , Health Personnel , Humans , Seroconversion
15.
Transfus Med Hemother ; 48(3): 154-160, 2021 May.
Article in English | MEDLINE | ID: covidwho-1247451

ABSTRACT

BACKGROUND: The SARS-CoV-2 pandemic has challenged many of our current routine practices in the treatment and care of patients. Given the critical importance of blood donation and transfusion we analyzed 92 blood samples of individuals infected with SARS-CoV-2 stratified by symptoms. STUDY DESIGN AND METHODS: We therefore tested blood samples for SARS-CoV-2 via RT-PCR targeting the E gene. In addition, we tested each blood sample for anti-SARS-CoV-2 IgG antibodies via ELISA and performed plaque reduction neutralization tests. RESULTS: SARS-CoV-2 RNA was absent in the blood of mild to asymptomatic patients (57 individuals) and only detectable in individuals with severe COVID-19 who were admitted to the intensive care unit (35 individuals) (n = 6/92 [6.5%]; p = 0.023 Fisher's exact test). Interestingly, anti-spike IgG antibodies were not significantly higher in intensive care unit patients compared to mild patients, but we found that their neutralizing capacity was disproportionately increased (p < 0.001). CONCLUSION: Our observations support the hypothesis that there are no potential hazards from blood or plasma transfusion of SARS-CoV-2-positive individuals with mild flu-like symptoms and more importantly of asymptomatic individuals.

16.
iScience ; 24(4): 102311, 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1129054

ABSTRACT

We describe a physics-based learning model for predicting the immunogenicity of cytotoxic T lymphocyte (CTL) epitopes derived from diverse pathogens including SARS-CoV-2. The model was trained and optimized on the relative immunodominance of CTL epitopes in human immunodeficiency virus infection. Its accuracy was tested against experimental data from patients with COVID-19. Our model predicts that only some SARS-CoV-2 epitopes predicted to bind to HLA molecules are immunogenic. The immunogenic CTL epitopes across all SARS-CoV-2 proteins are predicted to provide broad population coverage, but those from the SARS-CoV-2 spike protein alone are unlikely to do so. Our model also predicts that several immunogenic SARS-CoV-2 CTL epitopes are identical to seasonal coronaviruses circulating in the population and such cross-reactive CD8+ T cells can indeed be detected in prepandemic blood donors, suggesting that some level of CTL immunity against COVID-19 may be present in some individuals before SARS-CoV-2 infection.

17.
Nat Commun ; 12(1): 1112, 2021 02 18.
Article in English | MEDLINE | ID: covidwho-1091491

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNα and IFNλ levels when compared to non-severe COVID-19 patients. In a mouse model of pulmonary HSV-1 infection, treatment with recombinant IL-3 reduces viral load and mortality. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating pDCs into the airways by stimulating CXCL12 secretion from pulmonary CD123+ epithelial cells, both, in mice and in COVID-19 negative patients exhibiting pulmonary diseases. This study identifies IL-3 as a predictive disease marker for SARS-CoV-2 infections and as a potential therapeutic target for pulmunory viral infections.


Subject(s)
COVID-19/diagnosis , Interleukin-3/blood , Animals , COVID-19/mortality , Chemokine CXCL12/immunology , Dendritic Cells/cytology , Disease Models, Animal , Female , Germany , Humans , Immunity, Innate , Interferons/blood , Lung/immunology , Lung/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Prospective Studies , Severity of Illness Index , T-Lymphocytes/cytology , Viral Load
18.
Nat Commun ; 11(1): 5829, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-933682

ABSTRACT

A SARS-CoV2 super-spreading event occurred during carnival in a small town in Germany. Due to the rapidly imposed lockdown and its relatively closed community, this town was seen as an ideal model to investigate the infection fatality rate (IFR). Here, a 7-day seroepidemiological observational study was performed to collect information and biomaterials from a random, household-based study population. The number of infections was determined by IgG analyses and PCR testing. We found that of the 919 individuals with evaluable infection status, 15.5% (95% CI:[12.3%; 19.0%]) were infected. This is a fivefold higher rate than the reported cases for this community (3.1%). 22.2% of all infected individuals were asymptomatic. The estimated IFR was 0.36% (95% CI:[0.29%; 0.45%]) for the community and 0.35% [0.28%; 0.45%] when age-standardized to the population of the community. Participation in carnival increased both infection rate (21.3% versus 9.5%, p < 0.001) and number of symptoms (estimated relative mean increase 1.6, p = 0.007). While the infection rate here is not representative for Germany, the IFR is useful to estimate the consequences of the pandemic in places with similar healthcare systems and population characteristics. Whether the super-spreading event not only increases the infection rate but also affects the IFR requires further investigation.


Subject(s)
COVID-19/etiology , COVID-19/mortality , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/transmission , COVID-19 Testing/statistics & numerical data , Child , Comorbidity , Family Characteristics , Female , Germany/epidemiology , Humans , Immunoglobulin G/blood , Male , Middle Aged , Mortality , Polymerase Chain Reaction , Prevalence , SARS-CoV-2/genetics , Young Adult
19.
Cell ; 183(6): 1508-1519.e12, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-898562

ABSTRACT

The urgent need for an effective SARS-CoV-2 vaccine has forced development to progress in the absence of well-defined correlates of immunity. While neutralization has been linked to protection against other pathogens, whether neutralization alone will be sufficient to drive protection against SARS-CoV-2 in the broader population remains unclear. Therefore, to fully define protective humoral immunity, we dissected the early evolution of the humoral response in 193 hospitalized individuals ranging from moderate to severe. Although robust IgM and IgA responses evolved in both survivors and non-survivors with severe disease, non-survivors showed attenuated IgG responses, accompanied by compromised Fcɣ receptor binding and Fc effector activity, pointing to deficient humoral development rather than disease-enhancing humoral immunity. In contrast, individuals with moderate disease exhibited delayed responses that ultimately matured. These data highlight distinct humoral trajectories associated with resolution of SARS-CoV-2 infection and the need for early functional humoral immunity.


Subject(s)
COVID-19 , Immunity, Humoral , Immunoglobulin A/immunology , Immunoglobulin M/immunology , Receptors, IgG/immunology , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/mortality , Female , HL-60 Cells , Humans , Male
20.
Infect Dis Ther ; 9(4): 837-849, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-743789

ABSTRACT

BACKGROUND: Serology testing is explored for epidemiological research and to inform individuals after suspected infection. During the coronavirus disease 2019 (COVID-19) pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist. METHODS: In a large German university hospital, we performed weekly questionnaire assessments and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements with various commercial tests, a novel surrogate virus neutralisation test, and a neutralisation assay using live SARS-CoV-2. RESULTS: From baseline to week 6, 1080 screening measurements for anti-SARS CoV-2 (S1) IgG from 217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12.4% in week 6, p < 0.001). In sera of convalescent patients with PCR-confirmed COVID-19, we measured high anti-SARS-CoV-2 IgG levels, obtained highly concordant results from enzyme-linked immunosorbent assays (ELISA) using e.g. the spike 1 (S1) protein domain and the nucleocapsid protein (NCP) as targets, and confirmed antiviral neutralisation. However, in HCP the cumulative incidence for anti-SARS-CoV-2 (S1) IgG was 1.86% for positive and 0.93% for equivocal positive results over the study period of 6 weeks. Except for one HCP, none of the eight initial positive results were confirmed by alternative serology tests or showed in vitro neutralisation against live SARS-CoV-2. The only true seroconversion occurred without symptoms and mounted strong functional humoral immunity. Thus, the confirmed cumulative incidence for neutralizing anti-SARS-CoV-2 IgG was 0.47%. CONCLUSION: When assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, we suggest confirming positive results from single measurements by alternative serology tests or functional assays. Our data highlight the need for a methodical serology screening approach in regions with low SARS-CoV-2 infection rates. TRIAL REGISTRATION: The study is registered at DRKS00021152.

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