key: cord-0893241-2kb6owyq
authors: Dehnen, Dorothea; Dehnen, Katja; Trilling, Mirko; Fiedler, Melanie; Drexler, Julia; Goralski, Marcel; Le‐Trilling, Vu Thuy Khanh; Schöler, Lara; Jöckel, Karl‐Heinz; Heßbrügge, Martina
title: Discrepancy between frequent occurrence of COVID‐19‐like symptoms and low seroconversion rates among healthcare workers
date: 2021-10-18
journal: J Med Virol
DOI: 10.1002/jmv.27385
sha: c3f4b2fa3af53da696bbfac5d0fe01970568f807
doc_id: 893241
cord_uid: 2kb6owyq

During the first wave of the pandemic, we compared the occurrence of subjectively experienced COVID‐19‐like symptoms and true severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) seroconversion rates among medical personnel in general practices. This cross‐sectional study determined the SARS‐CoV‐2‐specific immunoglobulin G (IgG) antibody status of medical staff from 100 outpatient practices in Germany. Study cohort characteristics and COVID‐19‐like symptoms were obtained by questionnaires. The initial screening for SARS‐CoV‐2‐recognizing antibodies was performed using a commercial chemiluminescence microparticle immunoassay. Positive results were controlled with another approved test. Samples with discrepant results were subjected to a third IgG‐binding assay and a neutralization test. A total of 861 participants were included, 1.7% (n = 15) of whom tested positive for SARS‐CoV‐specific IgG in the initial screening test. In 46.6% (n = 7) of positive cases, test results were confirmed by an independent test. In the eight samples with discrepant results, neither spike‐specific antibodies nor in vitro neutralizing capacity were detectable, resulting in a genuine seroprevalence rate of 0.8%. 794 participants completed the questionnaire. Intriguingly, a total of 53.7% (n = 426) of them stated episodes of COVID‐19‐like symptoms. Except for smell and taste dysfunction, there were no significant differences between the groups with and without laboratory‐confirmed SARS‐CoV‐2 seroconversion. Our results demonstrated that only 0.8% of participants acquired SARS‐CoV‐2 even though 53.7% of participants reportedly experienced COVID‐19‐like symptoms. Thus, even among medical staff, self‐diagnosis based on subjectively experienced symptoms does not have a relevant predictive value.

compared with the general population. 3 Worldwide, the data on the seroprevalence of SARS-CoV-2 in HCW differ significantly with an overall seroprevalence of 8.7% (North America 12.7%, Europe 8.5%). 4 In studies among HCWs in the northern metropolitan region of Barcelona, Spain (10.3%) 5 and in Sweden (19.1%), 6 the seroprevalence was even higher. In contrast, studies among clinic personnel from Germany showed significantly lower values with a seroprevalence between 1% and 4.36%. [7] [8] [9] However, until now-at least to our knowledge-data on infection rates among medical staff in the outpatient sector are limited.

Almost all SARS-CoV-2-infected individuals develop at least one type of specific immunoglobulin (Ig) such as IgM, IgA or IgG, which remain detectable in most symptomatic patients for a 6-month period. [10] [11] [12] [13] [14] [15] Given the phylogenetic relationship as well as the genetic and antigenetic similarity between human coronaviruses (hCoV), a certain cross-reactivity between the immune response triggered by seasonal hCoVs and SARS-CoV-2 may occur. A straightforward solution to solve potential specificity issues is the implementation of a two-or multi-layered testing strategy based on an initial screening test followed by one or more validation tests.

The course of COVID-19 is highly variable, ranging from asymptomatic to mild and moderate to severe as well as critical cases. 16 Since COVID-19 symptoms are highly nonspecific, according to the Cochrane COVID-19 Diagnostic Test Accuracy Group neither the presence nor the absence of a particular symptom can be considered a COVID-19 disease.

In this context, anosmia or ageusia could be a red flag and fever or cough could also be symptoms that should trigger early testing for SARS-CoV-2. 17 So far, to our knowledge, there are few data from the outpatient sector examining whether SARS-CoV-2-specific diagnostics are also essential for healthcare professionals or whether an individual assessment based on subjective reports of experiencing symptoms is sufficient.

Hundred registered GP participated in the study. The network is supraregional, with practices being evenly distributed throughout NRW, Germany. In total, 861 doctors and medical staff members took part in the study and provided blood samples for the antibody determination. Of the 861 study participants, 87.1% (n = 750) were female. The questionnaire was completed by 92.2% (n = 794) of participants. Most participants were medical assistants (73.8%, n = 586), while 26.2% (n = 208) were medical doctors. The mean age of participants was 42.6 years (17-80 years); 34.4% (n = 273) were 50 years or older. For more details, see Table 1 .

Study participants received the required material for blood sampling and the questionnaires by mail or by the laboratory's courier service.

Blood samples were drawn in June 2020 by the practice staff and T A B L E 1 Description of the characteristics of the total cohort (n = 794) and the cohort with a positive confirmatory test collected and analyzed by the laboratory "Labor im Westen". Since three recruited practices were on vacation at the time, their serum samples were collected and analyzed in July 2020.

The initial SARS-CoV-2 IgG screening was conducted using the Note: Describes the results of the antibody determination for SARS-CoV-2 and the result of the neutralization test. First the CMIA from Abbott was applied and afterwards a second test with Liaison SARS-CoV-2 S1/S2 IgG (CMIA; DiaSorin) was used to validate the results. Discordant results were subjected to further analysis using the EUROIMMUN Anti-SARS-CoV-2 ELISA (Lübeck, Germany) on the one hand and an automated SARS-CoV-2 neutralization test based on an in-cell ELISA on the other hand.

Abbreviations: ELISA, enzyme-linked immunoassay; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. in Europe, with seroprevalence rates between 1.6% and 7.4%. [21] [22] [23] To our knowledge, only one other study focusing on the outpatient sector has been conducted in Germany so far, namely a seroprevalence study among 151 employees of a primary care facility (medical care center, MVZ) with eight locations in Bavaria. Here, a higher seroprevalence rate of 2.4% was reported, but it must be noted that a confirmatory test was not part of the study protocol. 24 With a total of 100 practices across NRW and given the different Additionally, this study revealed a discrepancy between the subjective experience that apparently felt like COVID-19 in contrast to real SARS-CoV-2 infections. Interestingly, more than half of the respondents reported at least one symptom that was compatible with COVID-19, while only a minority showed seroconversion. In our study, only the symptoms smell and taste dysfunction differed significantly; other symptoms such as sore throat, headache, and fatigue did not differ significantly and were similarly common in both the group with and the group without SARS-CoV-2 seroconversion. Although we found a significant difference only in the symptoms smell and taste dysfunction, these symptoms do not appear to be exclusive to COVID-19, as 1.4% and 2.2% of those without seroconversion mentioned them.

Furthermore, it is noteworthy that many practice personnel reported episodes of symptoms compatible with COVID-19 but only a fraction of them were tested by RT-qPCR. In the initial phase of the pandemic, the SARS-CoV-2 test capacities were limited and the Robert Koch-Institute recommended a test only if typical symptoms were present, upon returning from defined risk areas, or after contact with a confirmed COVID-19 case. 25 A very important issue here is that the misconception of having had a SARS-CoV-2 infection caused F I G U R E 2 Comparison of COVID-19 symptoms reported during the observational period of HCWs who tested positive (n = 7) and negative (n = 787) in %. ***p < 0.000. describes the COVID-19-like symptoms of HCWs who tested positive (n = 7) and negative between February and July, 2020. HCW, healthcare worker not only anxiety and stress, but also led to false assumptions regarding acquired immunity. This could result in neglect of the use of protective measures, vaccination hesitancy, and finally an increased risk of infections. Extensive education and testing as early as possible would be desirable to counteract this uncertainty.

In summary, even among medical staff, self-diagnosis based on subjectively experienced symptoms lacks predictive value. Accordingly, early and broad testing is indispensable due to the unspecific nature of COVID-19 symptoms.

GPs are an essential part of the German healthcare system and until now the data on infection rates among medical staff in the outpatient sector are scarce. This study is one of the first to provide detailed data on SARS-CoV-2 infection rates among medical staff in GPs. One of the strengths of the study is certainly that the test results for SARS-CoV-2 IgG antibodies were verified with two validation tests as well as with a neutralization test. A study by Cervia et al. 26 showed that systemic IgG antibody production depends on the severity of the disease. Antibody responses appear to be less sustained following asymptomatic infections and/or in patients who experience only mild symptoms. 26 Thus, it cannot be completely ruled out that the humoral immune response in some participants, in particular following asymptomatic or very mild COVID-19 course, waned to a point where SARS-CoV-2-specific antibodies were below the level of detection. In this regard, however, other studies argue in favor of more sustained IgG responses especially after symptomatic COVID-19 infection. 12 In view of the overall sample size, one limitation is the small number of subjects with a positive test result, which limits the applicability of statements about the participants with a positive test result. Larger study populations are required for further analyses.

The present study shows that COVID-19 infection rates among medical staff in GPs in NRW in Germany remained low during the first wave of the pandemic. Furthermore, an individual assessment based on experienced symptoms has no or very little predictive value even among medical staff.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

We would like to thank all the employees of the laboratory "Labor im 

http://orcid.org/0000-0003-3659-3541

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