key: cord-0693510-fvhdduwj authors: Blom, Kjersti B.; Åsberg, Anders; Sjaastad, Ivar; Kalleberg, Karl T.; Søraas, Arne; Midtvedt, Karsten; Birkeland, Jon A. title: Kidney Transplant Recipient Behavior During the Early COVID-19 Pandemic: A National Survey Study in Norway date: 2021-11-17 journal: Kidney Med DOI: 10.1016/j.xkme.2021.09.006 sha: 169f17fb5dcc5c70b7a6a8a32df02443f7686646 doc_id: 693510 cord_uid: fvhdduwj RATIONALE & OBJECTIVE: Studies published from countries with a high prevalence of COVID-19 have found increased incidence and a more severe disease course of COVID-19 in kidney transplant recipients than in the general population. We investigated how the first wave of the COVID-19 pandemic affected the everyday life of kidney transplant recipients in a country with a low infection burden. STUDY DESIGN: Prospective case control study. SETTING & PARTICIPANTS: All adult kidney transplant recipients in Norway with a functioning graft and listed in the public phone registry (n=3,060) and a group of randomly recruited individuals > 18 years from the general population (n=20000) were invited to participate in the study by an SMS text message. In parallel, all kidney transplant recipients in Norway were invited to measure SARS-CoV2 IgG from mid-June to October. PREDICTORS: The participants were asked to fill out a questionnaire focused on everyday life, travel history, exposure to known COVID-19 cases, and demographics. ANALYTICAL APPROACH: Groups were compared with independent tests utilizing two-sided 0.05 significance levels. RESULTS: A total of 1,007 kidney transplant recipients and 4,409 controls answered the questionnaire. The kidney transplant recipients reported being more concerned about a SARS-CoV-2 infection (27%) than the control group (7%, p-value <0.001); i.e., they behaved more carefully in their everyday life (not going to the grocery store; 0.9% vs. 5.9 %, P<0.001, keeping at least one-meter distance; 5.8% vs. 16.6%, <0.001). Of the kidney transplant responders, 81% had a SARS-CoV2 IgG taken; all were negative. LIMITATIONS: Mortality data is not reliable due to the low number of SARS-CoV-2 infected kidney transplant recipients in Norway. The relatively low questionnaire response rate for kidney transplant recipients is not optimal. CONCLUSIONS: The questionnaire shows that kidney transplant recipients have behaved more carefully compared to the general population with less social interaction and a very high degree of adherence to governmental advice. Coronavirus disease 2019 (COVID-19) rapidly spread worldwide and was declared a pandemic by the World Health Organization (WHO) in March 2020 1 . It was soon recognized that healthy individuals of any age could experience severe illness and death. This led to different scenarios varying from country to country but often involving office and factory shut-downs and restrictions placed on social interactions. Media was flooded daily with COVID-19 horror stories and scenarios. People were scared, and the medical knowledge was limited. As more COVID-19 specific information was encountered, most of the patients ending up in intensive care units (ICUs) were found to be older adults, often with underlying medical conditions [2] [3] [4] [5] [6] . Comorbidities such as hypertension, diabetes, cardiovascular disease, and chronic kidney disease were All adult kidney transplant recipients (n = 3,596) with a functioning graft as of April 20th, 2020, and a signed informed consent stating that data in the Norwegian Renal Registry (NRR) may be used for research were considered eligible to participate in the study. A search in the public phone registry among the 3,596 recipients yielded 3,060 to be eligible since 536 had reservations towards phone contact. Thus, 3,060 recipients were invited to participate in the study by SMS text messages. The questionnaire was available by logging on to a secure digital platform through a smartphone or a computer (fig 1) . A group of randomly recruited individuals > 18 years (n = 20.000) from the general by up to four reminders (answers received after the 27 th of May were omitted). To those responding to the first SMS-invitation, a second questionnaire was sent out on the 3rd of July, followed up by up to three reminders (answers received after the 12 th of August were omitted). The questionnaire focused on behavior in everyday life, travel history, exposure to known COVID-19 cases, living arrangements, history of diseases, and self-reported test results ( Table 1 ). The first questionnaire focused on the participants' behavior in the twoweek period before the lockdown or, if applicable, before they felt ill/were SARS-CoV-2 nasopharynx swab tested. The participants were also asked if they had experienced any symptoms of "light infections" the past six months (i.e. upper respiratory tract infections not requiring hospitalization, cystitis, or infection not requiring antibiotics). The followup questionnaire focused on the period between 7 th of July until 12 th of August. Simultaneously to the SMS study, all adult kidney transplant recipients (n = 3596) with a functioning graft and signed informed consent for registration in NRR were invited (by personal letter) to have a SARS-CoV-2 IgG blood test performed (free of charge) during mid-June to October. The test was most often performed in conjunction with a regular kidney transplant surveillance check-up. SARS-CoV-2 IgG measurements were initially performed by a multiplexed bead-based flow cytometric assay as previously described 11 . The test had a specificity of a 100% and a sensitivity of 84%. Positive and uncertain results were double-checked with a Roche Elecsys Anti-SARS-CoV-2 assay 12 . Demographic data on kidney transplant recipients who answered the questionnaire (kidney transplant responders) were compared to all remaining adult kidney transplant J o u r n a l P r e -p r o o f recipients registered in NNR to evaluate whether the kidney transplant responders were representative of the whole group (Table 2 ). Since the virus spread differently in urban vs. rural areas, a comparison was also made concerning geographic distribution within areas with high/low incidence of COVID-19. This comparison was made by dividing geographic areas into high and low prevalence areas based on the international classification (Red areas, ≥ 40 contaminated /100 000 habitants and Green areas; < 40 contaminated / 100 000 habitants over a 4-week period (±2 weeks from the first SMS was sent)), and classified kidney transplant responders and remaining kidney transplant recipients into residents of red or green areas at the time they answered the questionnaire. A similar analysis was done between kidney transplant responders and the control group. By November 1 st , 2020, the Norwegian Institute of Public Health (NIPH) reported 1,667,465 PCR tests performed. Among these, 19,563 were positive, and the number of deaths was 282 (5.2 per 100,000 inhabitants) 13 . Thus, Norway was categorized as a country with a low infection burden and COVID-19 rate during the first wave. Comparison of demographic data between recipients consenting to answer the questionnaire (kidney transplant responders) vs the remaining kidney transplant recipients was performed by the Norwegian Renal Registry (NRR). Data were analyzed with R (version 4.0.4) (data for table 1-2) and SPSS (data for table 3-5), using independent samples student t, Chi-squared test, or Fisher exact test. Results considered statistically significant when the P-value is equal to or below 0.05. J o u r n a l P r e -p r o o f The SMS part of the study was approved by the Norwegian ethics committee (REK 124170) and followed the Helsinki Declaration. It was registered in ClinicalTrials.gov (NTC 04320732). All participants were given information about the study via the digital platform and their right to withdraw from the study at any time. Consent forms were signed electronically. Data collection and storage were administered through the University of Oslo Services for Sensitive Data. The SARS-CoV-2 IgG screening was separately approved by the Norwegian ethics committee (REK 148904) and followed the Helsinki Declaration. Of the 3,060 kidney transplant recipients invited to participate in the SMS study, Table 2 ). The kidney transplant responders were more concerned about being exposed to SARS-CoV-2 infection (27%) than the control group (7%, p<0.001). This was also confirmed in both the age groups >= 65 years and < 65 years by the kidney transplant responders' behavior, as they reported being more careful in their everyday life to limit the risk of SARS-CoV-2 infection than the control group (table 3-5). Both during the two weeks before March 13, 2020, and the two weeks that directly followed, the kidney transplant responders in both age groups (>= 65 years and < 65 years) reported behaving more carefully compared to the control group in the respective age group (>= 65 years and < 65 years) with regards to going to the grocery store, going to the mall, keeping a distance of more than 1 meter from others in the store, and limiting social interactions. (table 5 ). We demonstrate that Norwegian kidney transplant study responders adhered closely to nationally initiated COVID-19 preventive measures. None of the kidney from France, a high-prevalence COVID-19 country, reported a higher prevalence among kidney transplant recipients (5%) compared to the general population (0,3%) 7 . In this report, kidney transplant recipients' mortality was substantially higher than among the general population (24% vs. 1%). In Norway, preliminary data indicate mortality at approximately 20% among kidney transplant recipients infected with SARS-CoV2 during the first wave 10 . Throughout the second and third waves, the mortality-rate in Norway seems somewhat reduced, with 7 deceased among 47 infected (14%) up to March 2021. It is known that exposure to a high viral load during contamination is correlated with a more serious COVID-19 disease 17-19 20 . Thus, one can suggest that cautious behavior is associated with less risk of viral transmission and consequently a milder disease. One could also speculate that the population pattern in Norway, with people living in remote areas and small cities yielding a low population density (15 persons/ km2 compared to 120/km2 in France), makes spreading of the SARS-CoV-2 more unlikely, and thus represents a "protective feature" of the country. During a pandemic, there are frequent distributions, specifically on social media, of misleading information. As kidney transplant responders were more concerned about infection with SARS-CoV-2 and simultaneously knew that immunosuppression was a "risk factor," one could assume that some would react to symptoms or suspicion of The present study has some limitations. First, the number of SARS-CoV-2 infected kidney transplant recipients in Norway is low, and mortality data is therefore not reliable. However, the second and third waves' mortality is still 14%, lower but comparable to reports from other European countries 10 . Second, the relatively low questionnaire response rate for kidney transplant recipients is not optimal. On the other hand, the comparison between the kidney transplant responders and all other kidney transplant recipients suggests that those answering the questionnaire are representative of the whole group regarding the risk of adverse COVID-19 outcome. Third, it may be possible that there is a selection bias, as the kidney transplant responders might be more careful than the rest of the kidney transplant population. However this would probably also be the case for the control group. Thus, our findings suggest that even though kidney transplant recipients might be at increased risk of SARS-CoV-2 infection and critical COVID-19 illness, Norwegian kidney transplant recipients as a group have been relatively "safe" during the first wave of COVID-19. The more careful social behavior of the recipients, and the low incidence of COVID-19 in the general population, are probably important contributors to this finding. Hopefully, a continuous watchful behavior will prevent increased mortality among kidney transplant recipients until the vaccine ends the pandemic. Elias "Red areas": geographical areas with ≥40 contaminated/100.000 inhabitants per ±2 weeks from 13th of March. Data analyzed with R and with independent samples student t or Chi-squared test. Data is presented as mean (±SD) or numbers (%). Abbreviations: BMI; body mass index, HLA; human leukocyte antigen, D; donor, R; recipient, ND; not determined, mTOR; mammalian target of rapamycin.*Combined with pancreas, liver or heart. §number of positive samples in relation to those taking a sample. Data analyzed with R and with independent samples student t or Chi-squared test. Data is presented as mean (±SD) or numbers (%). The kidney transplant responders behaved more carefully than the control group in both age groups (< and >= 65 years) in all areas except for domestic flights two weeks before the 13th of March. Data analyzed with SPSS and with Fisher exact test. Data is presented as numbers (%). The kidney transplant responders and the control group >=65 years behaved equally carefully with regards to domestic fligths. The kidney transplant responders and the control group behaved equally carefully with regards to international flights and avoiding meeting more than 50 people two weeks after the 13th of March in both age groups (< and >= 65 years). In all other areas, the kidney transplant responders behaved more carefully than the control group in both age groups (< and >= 65 years). Data analyzed with SPSS and with Fisher exact test. Data is presented as numbers (%). The kidney transplant responders and the control group behaved equally careful with regards to international flights in both age groups (< and >= 65 years) two weeks before answering the questionnaire in the period 03.0702020-12.08.2020.. In all other areas the kidney transplant responders behaved more carefully than the control group in both age groups (< and >= 65 years). Data analyzed with SPSS and with Fisher exact test. Data is presented as numbers (%). 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Viruses Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1)pdm09 dose-finding investigational new drug study Development of a dose-response model for SARS coronavirus Kinetics of viral load and antibody response in relation to COVID-19 severity. The Journal of clinical investigation Received SMS invitation n = 3,060Completed the survey n = 1,007