Community seroprevalence of COVID-19 in probable and possible cases at primary health care centres in Spain

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Abstract

Background

There is a scarcity of information about patients with mild or moderate symptoms during the coronavirus disease 2019 (COVID-19). This is especially true for those who attended and were followed up at primary care settings.

Objectives

We aim to measure the seroprevalence of antibodies against SARS-CoV-2 infection in a community sample of possible cases and among probable cases followed in primary care.

Methods

We selected a random sample of 600 individuals stratified by age groups from a total population of 19 899 individuals from a community area in Barcelona. We also invited all the patients that had been followed by General Practitioners (GPs). For both populations, we used COVID-19 rapid lateral flow immunoassays, which qualitatively assess the presence of patient-generated Immunoglobulins G (IgG) and Immunoglobulin M (IgM).

Results

Three hundred and eleven asymptomatic individuals from the randomly selected sample participated in the study. The mean age was 43.7 years [standard deviation (SD) = 21.79] and 55% were women. Seventeen individuals were seropositive for IgM and/or IgG, resulting in an overall prevalence of 5.47% (95% confidence interval = 3.44–8.58). Six hundred and thirty-four symptomatic patients were followed up by GPs. The mean age was 46.97 years (SD = 20.05) and 57.73% were women. Of these, 244 patients (38.49%) were seropositive. Results of the multivariate logistic regression analysis showed that the odds ratio for a positive test was significantly increased in patients who had fever, ageusia and contact with a patient diagnosed with COVID-19.

Conclusions

The seroprevalence of antibodies against SARS-CoV-2 among possible cases was lower than expected. Approximately, 40% of the symptomatic patients followed up by GPs during the peak months of the pandemic were positive.

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  1. Our take

    This study, available as a preprint and thus not yet peer reviewed, used an asymptomatic community-based sample from Spain of 311 participants, and a symptomatic sample identified via primary physicians of 634 patients to estimate the prevalence of prior SARS-CoV-2 infection. Of the 311 asymptomatic people, 17 tested positive for SARS-CoV-2 antibodies (5.47%) while of the 634 symptomatic people, 244 (38.49%) tested positive. People testing positive for antibodies had higher statistical odds of symptoms in the past 2 months, though this resulted in, on average, roughly 1 more symptom in those with than those without prior infection. There was notable discrepancy between self-reported prior PCR-confirmed infection and the study’s antibody test results, which suggests that reliance on antibody testing may result in false negatives, and undercount the total number infected. Still, this study assesses the seroprevalence of past infection in an area that was hard-hit by the pandemic, across both symptomatic and asymptomatic individuals and overall found that many in the population likely remain susceptible to SARS-CoV-2.

    Study design

    cross-sectional;prospective-cohort

    Study population and setting

    The study objective was to identify the seroprevalence of SARS-CoV-2 antibodies in Barcelona, Spain from April 21 to 24, 2020 among a random, age-stratified sample of 311 persons in the community who did not have a suspected case of COVID-19 and previously had not tested positive, and from April 29 to May 5, 2020, among 634 patients with COVID-19 symptoms being followed by a general physician. Patients from the community sample were randomly selected from a total of 19,899 individuals registered at a single primary healthcare center in Barcelona. The symptomatic patients were derived from a sample of 743 that had all consulted a primary care physician with COVID-19 symptoms between March 2 and April 24, 2020 either in-person or remotely, and were followed with routine phone calls to assess symptoms until they resolved. The study also included a standardized questionnaire in both groups about symptoms, visits to the emergency department or hospitalization, and participant gender.

    Summary of main findings

    The study found that, of the 311 asymptomatic participants, 17 were seropositive for IgM and/or IgG (5.47%, 95% CI: 3.44 – 8.58%). Of 634 symptomatic participants, 244 (38.49%, 95% CI: 34.78 – 42.33%) were seropositive. During follow-up, 21.1% of those symptomatic went to the ED and 11.8% were hospitalized. 41 patients had received a SARS-CoV-2 PCR test prior to the antibody test, and 25 (61.0%) were positive. Only 16 out of these 25 (64.0%) tested positive for IgG antibodies during the study. The study also found that positive cases for SARS-CoV-2 IgM/IgG had statistically significant odds of having had contact with other positive cases, having attended the ED, or being hospitalized, compared to those asymptomatic. Among those with symptoms, those with a positive antibody test were also significantly more likely to have had any symptoms (88.1%) compared to those with a negative test (81.0%), though the mean number of symptoms among those testing positive was only about 1 symptom higher than those testing negative.

    Study strengths

    The study assessed symptoms and tested for antibodies among both those who contacted a physician and those who were asymptomatic in the community. They used a standardized questionnaire for symptom assessment, which increases comparability to other studies. They used a randomly selected sample from the community to reduce selection bias and thus attempt to maximize the representativeness of the sample.

    Limitations

    Despite attempts to increase representativeness, there was a reduced response rate among the asymptomatic sample (response rate 52%) which could have impacted results if those who agreed to participate differed from those who did not. Major reasons noted for non-response included being contacted via phone, stopping quarantine in order to attend the study, and concerns around comorbidities, which may result in a healthier (and less exposed) sample included in the study than they would have otherwise had. There was also notable disagreement between participants who received a positive PCR test in the past, versus those who received a positive antibody test in this study, which may have been the result of reporting bias, issues with validity of the specific antibody test the study team used or potential natural variation in the antibody response. Additionally, potential limitations related to the performance diagnostics of the antibody test were not explored, and the definition of an asymptomatic individual, including how many symptoms that they may have presented with and still been considered asymptomatic, was not adequately described potentially resulting in misclassification of asymptomatic cases.

    Value added

    This study assessed both a symptomatic and asymptomatic population in Barcelona, Spain, an area that was significant impacted by the pandemic, and assessed SARS-CoV-2 antibodies to look at the population prevalence of past infection.

  2. SciScore for 10.1101/2020.06.13.20130575: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: All adult participants provided verbal consent to participate in the survey.
    IRB: The study design was reviewed and approved by the ethics committee of the Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol) (number 20/104-P).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All the analyses were conducted using the STATA 14 version.
    STATA
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    One of the limitations of our study is that characteristics of serological immunoassay tests may not be sufficiently explored and validated [13]. We did not perform RT-PCR to the IgM positive cases, thus we could not confirm if these individuals were infected. The WHO stated that serological tests, could be susceptible to cross-reaction with other frequent infections, like human coronaviruses causing common cold [14]. Nonetheless, despite their limitations, serology testing for COVID-19 are useful to better quantify the number of cases of COVID-19, including those that may be asymptomatic or have recovered (13).

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.