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1. Impact of baseline SARS-CoV-2 antibody status on syndromic surveillance and the risk of subsequent COVID-19-a prospective multicenter cohort study.

Author

Kohler P, Güsewell S, Seneghini M, Egger T, Leal O, Brucher A, Lemmenmeier E, Möller JC, Rieder P, Ruetti M, Stocker R, Vuichard-Gysin D, Wiggli B, Besold U, Kuster SP, McGeer A, Risch L, Friedl A, Schlegel M, Vernazza P, and Kahlert CR

Subjects
Cohort Studies, Health Personnel, Humans, Prospective Studies, Sentinel Surveillance, COVID-19, SARS-CoV-2
Abstract

Background: In a prospective healthcare worker (HCW) cohort, we assessed the risk of SARS-CoV-2 infection according to baseline serostatus., Methods: Baseline serologies were performed among HCW from 23 Swiss healthcare institutions between June and September 2020, before the second COVID-19 wave. Participants answered weekly electronic questionnaires covering information about nasopharyngeal swabs (PCR/rapid antigen tests) and symptoms compatible with coronavirus disease 2019 (COVID-19). Screening of symptomatic staff by nasopharyngeal swabs was routinely performed in participating facilities. We compared numbers of positive nasopharyngeal tests and occurrence of COVID-19 symptoms between HCW with and without anti-nucleocapsid antibodies., Results: A total of 4812 HCW participated, wherein 144 (3%) were seropositive at baseline. We analyzed 107,807 questionnaires with a median follow-up of 7.9 months. Median number of answered questionnaires was similar (24 vs. 23 per person, P = 0.83) between those with and without positive baseline serology. Among 2712 HCW with ≥ 1 SARS-CoV-2 test during follow-up, 3/67 (4.5%) seropositive individuals reported a positive result (one of whom asymptomatic), compared to 547/2645 (20.7%) seronegative participants, 12 of whom asymptomatic (risk ratio [RR] 0.22; 95% confidence interval [CI] 0.07 to 0.66). Seropositive HCWs less frequently reported impaired olfaction/taste (6/144, 4.2% vs. 588/4674, 12.6%, RR 0.33, 95% CI 0.15-0.73), chills (19/144, 13.2% vs. 1040/4674, 22.3%, RR 0.59, 95% CI 0.39-0.90), and limb/muscle pain (28/144, 19.4% vs. 1335/4674, 28.6%, RR 0.68 95% CI 0.49-0.95). Impaired olfaction/taste and limb/muscle pain also discriminated best between positive and negative SARS-CoV-2 results., Conclusions: Having SARS-CoV-2 anti-nucleocapsid antibodies provides almost 80% protection against SARS-CoV-2 re-infection for a period of at least 8 months., (© 2021. The Author(s).)

Published
2021
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2. Non-occupational and occupational factors associated with specific SARS-CoV-2 antibodies among hospital workers - A multicentre cross-sectional study.

Author

Kahlert CR, Persi R, Güsewell S, Egger T, Leal-Neto OB, Sumer J, Flury D, Brucher A, Lemmenmeier E, Möller JC, Rieder P, Stocker R, Vuichard-Gysin D, Wiggli B, Albrich WC, Babouee Flury B, Besold U, Fehr J, Kuster SP, McGeer A, Risch L, Schlegel M, Friedl A, Vernazza P, and Kohler P

Subjects
Adolescent, Adult, Aged, COVID-19 immunology, Cross-Sectional Studies, Female, Health Personnel, Humans, Male, Middle Aged, Multivariate Analysis, Occupational Diseases epidemiology, Occupational Diseases immunology, Risk Factors, Seroepidemiologic Studies, Sex Characteristics, Socioeconomic Factors, Switzerland epidemiology, Young Adult, Antibodies, Viral metabolism, COVID-19 epidemiology, Occupational Diseases virology, SARS-CoV-2 immunology
Abstract

Objectives: Protecting healthcare workers (HCWs) from coronavirus disease-19 (COVID-19) is critical to preserve the functioning of healthcare systems. We therefore assessed seroprevalence and identified risk factors for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) seropositivity in this population., Methods: Between 22 June 22 and 15 August 2020, HCWs from institutions in northern/eastern Switzerland were screened for SARS-CoV-2 antibodies. We recorded baseline characteristics, non-occupational and occupational risk factors. We used pairwise tests of associations and multivariable logistic regression to identify factors associated with seropositivity., Results: Among 4664 HCWs from 23 healthcare facilities, 139 (3%) were seropositive. Non-occupational exposures independently associated with seropositivity were contact with a COVID-19-positive household (adjusted OR 59, 95% CI 33-106), stay in a COVID-19 hotspot (aOR 2.3, 95% CI 1.2-4.2) and male sex (aOR 1.9, 95% CI 1.1-3.1). Blood group 0 vs. non-0 (aOR 0.5, 95% CI 0.3-0.8), active smoking (aOR 0.4, 95% CI 0.2-0.7), living with children <12 years (aOR 0.3, 95% CI 0.2-0.6) and being a physician (aOR 0.2, 95% CI 0.1-0.5) were associated with decreased risk. Other occupational risk factors were close contact to COVID-19 patients (aOR 2.7, 95% CI 1.4-5.4), exposure to COVID-19-positive co-workers (aOR 1.9, 95% CI 1.1-2.9), poor knowledge of standard hygiene precautions (aOR 1.9, 95% CI 1.2-2.9) and frequent visits to the hospital canteen (aOR 2.3, 95% CI 1.4-3.8)., Discussion: Living with COVID-19-positive households showed the strongest association with SARS-CoV-2 seropositivity. We identified several potentially modifiable work-related risk factors, which might allow mitigation of the COVID-19 risk among HCWs. The lower risk among those living with children, even after correction for multiple confounders, is remarkable and merits further study., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2021
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3. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01

Author

Weiner, January, Suwalski, Phillip, Holtgrewe, Manuel, Rakitko, Alexander, Thibeault, Charlotte, Müller, Melina, Patriki, Dimitri, Quedenau, Claudia, Krüger, Ulrike, Ilinsky, Valery, Popov, Iaroslav, Balnis, Joseph, Jaitovich, Ariel, Helbig, Elisa T, Lippert, Lena J, Stubbemann, Paula, Real, Luis M, Macías, Juan, Pineda, Juan A, Fernandez-Fuertes, Marta, Wang, Xiaomin, Karadeniz, Zehra, Saccomanno, Jacopo, Doehn, Jan-Moritz, Hübner, Ralf-Harto, Hinzmann, Bernd, Salvo, Mauricio, Blueher, Anja, Siemann, Sandra, Jurisic, Stjepan, Beer, Juerg H, Rutishauser, Jonas, Wiggli, Benedikt, Schmid, Hansruedi, Danninger, Kathrin, Binder, Ronald, Corman, Victor M, Mühlemann, Barbara, Arkal, Rao Arjun, Fragiadakis, Gabriela K, Mick, Eran, COMET, Consortium, Calfee, Carolyn S, Erle, David J, Hendrickson, Carolyn M, Kangelaris, Kirsten N, Krummel, Matthew F, Woodruff, Prescott G, Langelier, Charles R, Venkataramani, Urmila, García, Federico, Zyla, Joanna, Drosten, Christian, Alice, Braun, Jones, Terry C, Suttorp, Norbert, Witzenrath, Martin, Hippenstiel, Stefan, Zemojtel, Tomasz, Skurk, Carsten, Poller, Wolfgang, Borodina, Tatiana, Pa-COVID, Study Group, Ripke, Stephan, Sander, Leif E, Beule, Dieter, Landmesser, Ulf, Guettouche, Toumy, Kurth, Florian, and Heidecker, Bettina

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Coronaviruses, Emerging Infectious Diseases, Human Genome, Clinical Research, Infectious Diseases, Genetics, 2.1 Biological and endogenous factors, 2.5 Research design and methodologies (aetiology), Good Health and Well Being, SARS-CoV-2, COVID-19, Human Leukocyte Antigen&nbsp, intubation, Human Leukocyte Antigen, Clinical sciences, Health services and systems, Public health
Abstract

BackgroundSince the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing.MethodsWe analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS).FindingsWe describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles.InterpretationHLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2.FundingFunded by Roche Sequencing Solutions, Inc.

Published
2021

4. Risk and symptoms of COVID-19 in health professionals according to baseline immune status and booster vaccination during the Delta and Omicron waves in Switzerland-A multicentre cohort study

Author

Babouee Flury, Baharak, Güsewell, Sabine, Egger, Thomas, Leal, Onicio, Brucher, Angela, Lemmenmeier, Eva, Meier Kleeb, Dorette, Möller, J Carsten, Rieder, Philip, Rütti, Markus, Schmid, Hans-Ruedi, Stocker, Reto, Vuichard-Gysin, Danielle, Wiggli, Benedikt, Besold, Ulrike, McGeer, Allison, Risch, Lorenz, Friedl, Andrée, Schlegel, Matthias, Kuster, Stefan P, Kahlert, Christian R, and Kohler, Philipp

Subjects
SARS-CoV-2, Vaccination, Humans, COVID-19, 610 Medicine & health, Viral Vaccines, Prospective Studies, 610 Medizin und Gesundheit, Switzerland
Abstract

BACKGROUND Knowledge about protection conferred by previous Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and/or vaccination against emerging viral variants allows clinicians, epidemiologists, and health authorities to predict and reduce the future Coronavirus Disease 2019 (COVID-19) burden. We investigated the risk and symptoms of SARS-CoV-2 (re)infection and vaccine breakthrough infection during the Delta and Omicron waves, depending on baseline immune status and subsequent vaccinations. METHODS AND FINDINGS In this prospective, multicentre cohort performed between August 2020 and March 2022, we recruited hospital employees from ten acute/nonacute healthcare networks in Eastern/Northern Switzerland. We determined immune status in September 2021 based on serology and previous SARS-CoV-2 infections/vaccinations: Group N (no immunity); Group V (twice vaccinated, uninfected); Group I (infected, unvaccinated); Group H (hybrid: infected and ≥1 vaccination). Date and symptoms of (re)infections and subsequent (booster) vaccinations were recorded until March 2022. We compared the time to positive SARS-CoV-2 swab and number of symptoms according to immune status, viral variant (i.e., Delta-dominant before December 27, 2021; Omicron-dominant on/after this date), and subsequent vaccinations, adjusting for exposure/behavior variables. Among 2,595 participants (median follow-up 171 days), we observed 764 (29%) (re)infections, thereof 591 during the Omicron period. Compared to group N, the hazard ratio (HR) for (re)infection was 0.33 (95% confidence interval [CI] 0.22 to 0.50, p < 0.001) for V, 0.25 (95% CI 0.11 to 0.57, p = 0.001) for I, and 0.04 (95% CI 0.02 to 0.10, p < 0.001) for H in the Delta period. HRs substantially increased during the Omicron period for all groups; in multivariable analyses, only belonging to group H was associated with protection (adjusted HR [aHR] 0.52, 95% CI 0.35 to 0.77, p = 0.001); booster vaccination was associated with reduction of breakthrough infection risk in groups V (aHR 0.68, 95% CI 0.54 to 0.85, p = 0.001) and H (aHR 0.67, 95% CI 0.45 to 1.00, p = 0.048), largely observed in the early Omicron period. Group H (versus N, risk ratio (RR) 0.80, 95% CI 0.66 to 0.97, p = 0.021) and participants with booster vaccination (versus nonboosted, RR 0.79, 95% CI 0.71 to 0.88, p < 0.001) reported less symptoms during infection. Important limitations are that SARS-CoV-2 swab results were self-reported and that results on viral variants were inferred from the predominating strain circulating in the community at that time, rather than sequencing. CONCLUSIONS Our data suggest that hybrid immunity and booster vaccination are associated with a reduced risk and reduced symptom number of SARS-CoV-2 infection during Delta- and Omicron-dominant periods. For previously noninfected individuals, booster vaccination might reduce the risk of symptomatic Omicron infection, although this benefit seems to wane over time.

Published
2022

5. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01

Author

Weiner 3rd, January, Suwalski, Phillip, Holtgrewe, Manuel, Rakitko, Alexander, Thibeault, Charlotte, Müller, Melina, Patriki, Dimitri, Quedenau, Claudia, Krüger, Ulrike, Ilinsky, Valery, Popov, Iaroslav, Balnis, Joseph, Jaitovich, Ariel, Helbig, Elisa T., Lippert, Lena J., Stubbemann, Paula, Real, Luis M., Macías, Juan, Pineda, Juan A., Fernandez-Fuertes, Marta, Wang, Xiaomin, Karadeniz, Zehra, Saccomanno, Jacopo, Doehn, Jan-Moritz, Hübner, Ralf-Harto, Hinzmann, Bernd, Salvo, Mauricio, Blueher, Anja, Siemann, Sandra, Jurisic, Stjepan, Beer, Juerg H., Rutishauser, Jonas, Wiggli, Benedikt, Schmid, Hansruedi, Danninger, Kathrin, Binder, Ronald, Corman, Victor M., Mühlemann, Barbara, Arjun Arkal, Rao, Fragiadakis, Gabriela K., Mick, Eran, Consortium COMET, Calfee, Carolyn S., Erle, David J., Hendrickson, Carolyn M., Kangelaris, Kirsten N., Krummel, Matthew F., Woodruff, Prescott G., Langelier, Charles R., Venkataramani, Urmila, García, Federico, Zyla, Joanna, Drosten, Christian, Alice, Braun, Jones, Terry C., Suttorp, Norbert, Witzenrath, Martin, Hippenstiel, Stefan, Zemojtel, Tomasz, Skurk, Carsten, Poller, Wolfgang, Borodina, Tatiana, Study Group Pa-COVID, Ripke, Stephan, Sander, Leif E., Beule, Dieter, Landmesser, Ulf, Guettouche, Toumy, Kurth, Florian, Heidecker, Bettina, [Weiner, January] Charite Univ Med Berlin, Core Unit Bioinformat Berlin, Berlin Inst Hlth, DE-10178 Berlin, Germany, [Beule, Dieter] Charite Univ Med Berlin, Core Unit Bioinformat Berlin, Berlin Inst Hlth, DE-10178 Berlin, Germany, [Suwalski, Phillip] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Mueller, Melina] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Wang, Xiaomin] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Karadeniz, Zehra] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Skurk, Carsten] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Poller, Wolfgang] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Landmesser, Ulf] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Heidecker, Bettina] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Suwalski, Phillip] Charite, Berliner Simulat & Trainingszentrum, DE-10117 Berlin, Germany, [Holtgrewe, Manuel] Charite Univ Med Berlin, Berlin Inst Hlth, Core Unit Genom Berlin, DE-10178 Berlin, Germany, [Krueger, Ulrike] Charite Univ Med Berlin, Berlin Inst Hlth, Core Unit Genom Berlin, DE-10178 Berlin, Germany, [Zemojtel, Tomasz] Charite Univ Med Berlin, Berlin Inst Hlth, Core Unit Genom Berlin, DE-10178 Berlin, Germany, [Rakitko, Alexander] Genotek Ltd, Nastavnicheskii Pereulok 17-1, R-105120 Moscow, Russia, [Ilinsky, Valery] Genotek Ltd, Nastavnicheskii Pereulok 17-1, R-105120 Moscow, Russia, [Popov, Iaroslav] Genotek Ltd, Nastavnicheskii Pereulok 17-1, R-105120 Moscow, Russia, [Thibeault, Charlotte] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Helbig, Elisa T.] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Lippert, Lena J.] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Stubbemann, Paula] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Saccomanno, Jacopo] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Doehn, Jan-Moritz] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Huebner, Ralf-Harto] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Suttorp, Norbert] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Witzenrath, Martin] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Hippenstiel, Stefan] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Sander, Leif E.] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Kurth, Florian] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Patriki, Dimitri] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Jurisic, Stjepan] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Beer, Juerg H.] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Rutishauser, Jonas] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Wiggli, Benedikt] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Schmid, Hansruedi] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Quedenau, Claudia] Max Delbrueck Ctr Mol Med Berlin, DE-13125 Berlin, Germany, [Borodina, Tatiana] Max Delbrueck Ctr Mol Med Berlin, DE-13125 Berlin, Germany, [Balnis, Joseph] Albany Med Coll, Dept Mol & Cellular Physiol, Albany, NY 12208 USA, [Jaitovich, Ariel] Albany Med Coll, Dept Mol & Cellular Physiol, Albany, NY 12208 USA, [Real, Luis M.] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Macias, Juan] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Pineda, Juan A.] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Fernandez-Fuertes, Marta] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Hinzmann, Bernd] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Salvo, Mauricio] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Blueher, Anja] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Siemann, Sandra] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Guettouche, Toumy] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Danninger, Kathrin] Klinikum Wels Grieskirchen, Dept Cardiol & Intens Care, Wels, Austria, [Binder, Ronald] Klinikum Wels Grieskirchen, Dept Cardiol & Intens Care, Wels, Austria, [Corman, Victor M.] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Muehlemann, Barbara] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Drosten, Christian] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Jones, Terry C.] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Arkal, Rao Arjun] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Fragiadakis, Gabriela K.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Krummel, Matthew F.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Venkataramani, Urmila] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Arkal, Rao Arjun] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Fragiadakis, Gabriela K.] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Venkataramani, Urmila] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA, [Fragiadakis, Gabriela K.] Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA 94143 USA, [Mick, Eran] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Calfee, Carolyn S.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Hendrickson, Carolyn M.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Mick, Eran] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA, [Langelier, Charles R.] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA, [Mick, Eran] Chan Zuckerberg Biohub, San Francisco, CA USA, [Langelier, Charles R.] Chan Zuckerberg Biohub, San Francisco, CA USA, [Erle, David J.] COMET COVID 19 Multiphenotyping Effect Therapies, San Francisco, CA USA, [Consortium COMET] COMET COVID 19 Multiphenotyping Effect Therapies, San Francisco, CA USA, [Erle, David J.] Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA, [Kangelaris, Kirsten N.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA, [Arkal, Rao Arjun] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA, [Krummel, Matthew F.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, Sandler Asthma Basic Res Ctr, San Francisco, CA 94143 USA, [Garcia, Federico] Hosp Univ Clin San Cecilio, Inst Invest Ibs Granada, Granada, Spain, [Zyla, Joanna] Silesian Tech Univ, Dept Data Sci & Engn, Gliwice, Poland, [Alice, Braun] Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Charitepl 1, DE-10117 Berlin, Germany, [Ripke, Stephan] Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Charitepl 1, DE-10117 Berlin, Germany, [Jones, Terry C.] German Ctr Infect Res DZIF, Associated Partner Site, D-10117 Berlin, Germany, [Jones, Terry C.] Univ Cambridge, Ctr Pathogen Evolut, Dept Zool, Downing St, Cambridge CB2 3EJ, England, [Study Grp Pa-COVID] Pa COVID Study Grp, San Francisco, CA USA, [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet, Boston, MA 02114 USA, [Ripke, Stephan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA, [Landmesser, Ulf] Charite, Berlin Inst Hlth, Berlin, Germany, Roche Sequencing Solutions, Inc., Swiss National Science Foundation, Berlin Institutes of Health (B.I.H.), National Institutes of Health: NIH, Silesian University of Technology grant for Support and Development of Research Potential, NIAID-NIH CEIRS contract, NIH, German Research Foundation, German Ministry of Education and Research (BMBF), Berlin Institute of Health (CM-COVID), German Research Foundation (DFG), and Open Access Publication Fund of Charite - Universitatsmedizin Berlin

Subjects
SARS-CoV-2, Prevention, Major histocompatibility complex, Human Genome, COVID-19, Pneumonia, intubation, Human Leukocyte Antigen, Coronavirus, Vaccine Related, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, Clinical Research, FOS: Biological sciences, Human Leukocyte Antigen&nbsp, Genetics, Pneumonia & Influenza, 2.1 Biological and endogenous factors, Viral load, Aetiology, Lung, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, Research Paper
Abstract

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). Findings: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. Interpretation: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding: Funded by Roche Sequencing Solutions, Inc. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Published
2021

6. Impact of respirator versus surgical masks on SARS-CoV-2 acquisition in healthcare workers: a prospective multicentre cohort.

Author

Haller, Sabine, Güsewell, Sabine, Egger, Thomas, Scanferla, Giulia, Thoma, Reto, Leal-Neto, Onicio B., Flury, Domenica, Brucher, Angela, Lemmenmeier, Eva, Möller, J. Carsten, Rieder, Philip, Rütti, Markus, Stocker, Reto, Vuichard-Gysin, Danielle, Wiggli, Benedikt, Besold, Ulrike, Kuster, Stefan P., McGeer, Allison, Risch, Lorenz, and Schlegel, Matthias

Subjects
MEDICAL masks, MEDICAL personnel, SARS-CoV-2, RESPIRATORY protective devices, COVID-19
Abstract

Background: There is insufficient evidence regarding the role of respirators in the prevention of SARS-CoV-2 infection. We analysed the impact of filtering facepiece class 2 (FFP2) versus surgical masks on the risk of SARS-CoV-2 acquisition among Swiss healthcare workers (HCW). Methods: Our prospective multicentre cohort enrolled HCW from June to August 2020. Participants were asked about COVID-19 risk exposures/behaviours, including preferentially worn mask type when caring for COVID-19 patients outside of aerosol-generating procedures. The impact of FFP2 on (1) self-reported SARS-CoV-2-positive nasopharyngeal PCR/rapid antigen tests captured during weekly surveys, and (2) SARS-CoV-2 seroconversion between baseline and January/February 2021 was assessed. Results: We enrolled 3259 participants from nine healthcare institutions, whereof 716 (22%) preferentially used FFP2. Among these, 81/716 (11%) reported a SARS-CoV-2-positive swab, compared to 352/2543 (14%) surgical mask users; seroconversion was documented in 85/656 (13%) FFP2 and 426/2255 (19%) surgical mask users. Adjusted for baseline characteristics, COVID-19 exposure, and risk behaviour, FFP2 use was non-significantly associated with decreased risk for SARS-CoV-2-positive swab (adjusted hazard ratio [aHR] 0.8, 95% CI 0.6–1.0) and seroconversion (adjusted odds ratio [aOR] 0.7, 95% CI 0.5–1.0); household exposure was the strongest risk factor (aHR 10.1, 95% CI 7.5–13.5; aOR 5.0, 95% CI 3.9–6.5). In subgroup analysis, FFP2 use was clearly protective among those with frequent (> 20 patients) COVID-19 exposure (aHR 0.7 for positive swab, 95% CI 0.5–0.8; aOR 0.6 for seroconversion, 95% CI 0.4–1.0). Conclusions: Respirators compared to surgical masks may convey additional protection from SARS-CoV-2 for HCW with frequent exposure to COVID-19 patients. [ABSTRACT FROM AUTHOR]

Published
2022
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