key: cord-0799355-r65jod1f
authors: Rauber, C.; Tiwari-Heckler, S.; Pfeiffenberger, J.; Mehrabi, A.; Lund, F.; Gath, P.; Mieth, M.; Merle, U.; Rupp, C.
title: SARS-CoV-2 seroprevalence and clinical features of COVID-19 in a German liver transplant recipient cohort: a prospective serosurvey study.
date: 2020-10-04
journal: nan
DOI: 10.1101/2020.09.30.20204537
sha: 71472be51fbe6b0278e75bc0cf1465edf2ec3250
doc_id: 799355
cord_uid: r65jod1f

In liver transplant (LT) recipients with severe COVID-19 fatal outcome has been reported in a substantial subset of patients. Whether LT recipients are at increased risk for severe COVID-19 compared to the general population is controversial. Here we report the first results of a SARS-CoV-2 serosurvey in a large LT recipient cohort. Taking into account known risk factors, LT recipients a priori represented a high-risk cohort for severe COVID-19 with 101/219 (46.1 %) presenting with more than 2 risk factors for severe COVID-19. Out of 219 LT recipients 8 (3.7%) were either tested positive for nasopharyngeal SARS-CoV-2 RNA or anti-SARS-CoV-2 serum IgG. 5/8 (62.5 %) did not show any clinical signs of infection, 3/8 (37.5%) had self-limited disease, none required hospitalization for COVID-19. 5/8 (67.5%) SARS-CoV-2 positive patients showed high utilization of the healthcare system. 2/8 (25 %) had known exposure to infected health care personal. A majority of 65.4 % often or always avoided outside family social contacts. Face masks were commonly worn by all patients. In summary, LT recipients showed a SARS-CoV-2 seroconversion rate similar to the general population with a substantial percentage of unrecognized infections. The health care system can be the assumed source of infection in most of these cases.

exceeding the rate of the general population. [1] [2] [3] [4] In contrast, a swiss case study found mortality rates comparable to comorbidity matched non-transplant recipients. 5 Initial symptoms of COVID-19 patients are diverse. 6 Patients who tested positive for SARS-CoV2 can be asymptomatic or can develop COVID-19 and in severe cases may deteriorate due to acute respiratory distress syndrome with subsequent respiratory failure and death. 7 Both among the general population and SOT recipients the main risk factors for severe COVID-19 were older age and comorbidities like diabetes, obesity, renal and cardiopulmonary disease. [8] [9] [10] [11] Data on immunosuppression as a risk factor for COVID-19 is inconclusive, but minimization of immunosuppression (IS) has been widely recommended for LT patients with COVID-19 based on experience with other respiratory pathogens. 12 LT patients in most centers are therefore counselled to strictly follow hygiene and lifestyle restrictions to avoid SARS-CoV-2 infection. 13 It is not known to which extend this adv is effective to reduce SARS-CoV-2 infection in the LT recipient population. This study aims to define incidence and prevalence of SARS-CoV-2 infection and to explore the (preventive) effect of personal behavioural adjustments of LT recipients.

This prospective study was conducted between March 5th, 2020 and August 6th, 2020 at the University Hospital Heidelberg located in the German Bundesland of Baden-Württemberg. All study participants had undergone liver transplantation in the past and were older than 18 years.

All study participants provided written and informed consent before enrolment. The study was approved by the Ethics Committee of the Medical Faculty of the University of Heidelberg (approval number S-457/2020). The study was conducted in accordance with good clinical practice (GCP) and the Declaration of Helsinki.

Study enrollment was performed when patients presented for scheduled routine follow up after liver transplantation. Routine follow up on an outpatient basis is performed at least every six months at our center. After having provided written and informed consent, study participants completed a questionnaire querying information including demographics and behavior in the pandemic. Furthermore, study participants were asked to provide blood specimens and nasopharyngeal swabs. Blood was centrifuged and plasma was stored until analysis (-80°C).

Analyses were performed in batches at the central laboratory of the University Hospital Heidelberg Infectious Disease department. Anti-SARS-CoV-2 IgG (EUROIMMUN) were determined with enzyme-linked immunosorbent assays. The data sheet (April 29, 2020) reports cross-reactivities with anti-SARS-CoV-1-IgG-antibodies, but not with MERS-CoV-, HCoV-229E-, HCoV-NL63-, HCoV-HKU1-or HCoV-OC43-IgG antibodies.

Statistical analysis was carried out by a statistician using Graph Pad (Version 4.4.1), SPSS (Version 22) as appropriate. P values are given as indicated using chi-square test or nonparametric t-test.

We conducted a prospective study of 219 liver transplant recipients at a liver transplant center in the south of Germany with sample collection between may 5 th and august 6 th 2020. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted October 4, 2020. . & table 3, patient 1). All three clinically apparent COVID-19 cases were mild and self-limited. Patient 1 however showed severe blood test abnormalities with severe thrombocytosis, coagulopathy and elevated heart muscle enzymes. and FFP-2 masks (20.8 %) (figure 3, G) . 100% always wore masks in supermarkets and in hospitals and 16.3 % always wore masks outside.

We performed a prospective screening trial for SARS-CoV-2-RNA and anti-SARS-CoV-2-IgG infection in LT recipients during the COVID-19 pandemic in southern Germany. We documented acute or past SARS-CoV-2 infection in 3.7 % of our LT recipients during the study.

While direct serosurveys in the general population are lacking for our study region, the SARS-CoV-2 infected percentage in the population can be roughly estimated from serosurvey studies in other regions with similar health care setting. Until study termination about 37.000 PCR proven SARS-CoV-2 infections had been documented in the study area (Baden-Württemberg).

Recent German serosurveys provide a rough estimate of a factor 4 -10 of PCR documented SARS-CoV-2 infections to overall serological proven infections proposing a seroprevalence of 1.3-3.2 % in south-western Germany. 14,15 Taking into account this estimate, the prevalence of active or past SARS-CoV-2 infection in LT recipients is comparable to the general population.

Our direct study was limited to 219 patients that presented for routine follow up appointments after liver transplantation at our institution. However, the overall cohort comprises 1200 patients in the same region. These patients were encouraged to contact the transplant center in case of infection or hospital stay. Over the study period we did not record a single case of hospitalization or death due to COVID-19 in this cohort. The presented data shows an overall low but significant percentage of LT patients that had been infected with SARS-CoV-2. 5/8 patients serovconverted without experiencing any clinical overt symptom, in the other 3/8 patients clinical symptoms were mild and self-limited Interestingly, patient 2 (table 3) screened All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in 

The authors of this manuscript have nothing to disclose as described by the American Journal of Transplantation.

All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted October 4, 2020. . preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in

The copyright holder for this this version posted October 4, 2020. . perpetuity.

preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in

The copyright holder for this this version posted October 4, 2020. . https://doi.org/10.1101/2020.09.30.20204537 doi: medRxiv preprint perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted October 4, 2020. . https://doi.org/10.1101/2020.09.30.20204537 doi: medRxiv preprint Figure 3 All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted October 4, 2020. . https://doi.org/10.1101/2020.09.30.20204537 doi: medRxiv preprint

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