Anti COVID-19 immunity developed as assessed in a community-based oncological center

1Institut IMOR, Medical Institute for Radiotherapy and Oncology, Atrys Division, Barcelona, Spain 2Department of Radiation Oncology, University of California San Francisco (UCSF), CA 94158 California, USA 3Atrys Health, Madrid, Spain 4Laboratorios Cerba, Barcelona, Spain 5Fundació d’Investigació IMOR, Barcelona, Spain 6University of Barcelona, School of Medicine, Campus Casanova, Barcelona, Spain More Information


Introduction
Serology (antibody) tests for the SARS-CoV-2 have been proposed as an instrument to inform health authorities in order to take appropriate public health decisions during the pandemic [1]. Serology testing for COVID-19 may be used to determine wether an individual has been previously infected by SARS-CoV-2. Serological antiboidies are important to determine, because the polymerase chain reaction (PCR) identify the presence of viral material, which is found only in people who are currently infected. Not everyone who had the disease had the opportunity to be tested before the virus was cleared from their bodies, and estimates show that as many as 25% or more may have been asymptomatic [2,3]. Thus, we can presume that there is a signi icant part of the population that may have some degree of immunity. Because public health decision making relies in part on an understanding of the disease prevalence and the prevalence of immunity, extensive antibody/serology testing is needed to determine the true prevalence of SARS-CoV-2 infection. It is for this reason that we consider of great interest to communicate the immunization results obtained in our cohort.

Study design
This study was conducted between April 9 th , 2020 and May 8 th , 2020 in Barcelona, a city of 1,636,762 inhabitants in 2019, the second most populated city of Spain and the capital of Catalonia. Enrollment consisted on a group of HCW, their families, and general public that considered that had had the COVID-19 or had been in close contact with an infected. All participants provided written and informed consent before enrollment to have their data anonymously processed.
Testing was done according to the guidelines approved by the Spanish Ministerio de Sanidad, Instituto de Salud Carlos III [4] and the Conselleria de Salut of the Generalitat de Catalunya [5]. In summary, all HCW (including doctors, physicists, nurses, technicians, administrative and cleaning personnel) that might, to any degree, have been in contact with COVID-19 patients, the patients, their relatives or individuals who have been in contact with other infected patients, could be tested.
Cancer patients have been considered of higher risk of being infected by SARS-CoV-2 as well of having an increased severity of symptoms and higher mortality rate, so a special protocol for prevention of transmission among patients and health care workers was promptly applied in the cancer center in order to minimize risks. This protocol served as basis for the development of the national guidelines for radiation oncology services [6]. This protocol determined the use of extensive PCR and immunodetection exams periodically and as soon as any symptom or contact with infected individuals was suspected.

Procedures
Participants voluntarily contacted the center to be tested. After providing informed consent, participants completed a questionnaire including information about demographics, symptoms, underlying diseases, vaccinations, and medications they were taking. If no symptoms and no contact with possibly infected patients was detected, participants were excluded from the analysis.
Questionnaire data were recorded on site at the time of obtaining the samples and was introduced into an electronic data base (SPSS v15) by trained personnel for further statistical analysis.

Study design and study population
The main objective of this study was to determine the proportion of individuals infected with the SARS-CoV-2 or with immunity against it in the general population of Barcelona. The city that had a total of 17.163 positive cases (crude incidence rate of 104,86 cases per 10.000 inhabitants) and 38.241 considered as suspicious, according to the guidelines of the Conselleria de Sanitat of the Government of Catalonia [5]. These numbers approximately represent the 1.05% and 2.33% of the population respectively. Patients with PCR, Rapid diagnostic test (RDT) or enzyme-linked immunoabsorbent assay (ELISA) positive were considered positive meanwhile, patients classi ied as suspicious were individuals who had symptoms similar to those of con irmed covid-19 patients but who lacked a positive PCR or RDT.

Immunization results
A total of 521 participants were tested, 315 with ELISA and 206 with RDT.
Individuals without symptoms and without IgM or IgG were considered negative for SARS-CoV2. Patients with IgG and without IgM, were considered to have passed the infection. Patients with IgM (with or without IgG) were remitted to a PCR determination as well as patients with symptoms but without immunity (negative for IgM and IgG), as can be observed in table 1.
Of the 521 persons tested, 59 (11,32%) resulted positive to SARS-CoV-2. There were 47 patients who resulted positive for IgG in the group of 315 patients studied with ELISA (13,33%). In the group of 206 tested with RDT, there were a total of 17 patients (8,25%) with IgG positive (Table 2). In this Group, 4 (1,92%) patients probed to be positive for IgM, 2 (0,97%) of them in previously symptomatic patients and 2 (0,97%) in asymptomatic patients. All 4 were tested with PCR, the 2 previously symptomatic were negative and the 2 asymptomatic tested positive, thus considered as new diagnosis of COVID-19.  It is interesting to observe that there were 4 patients with previous positive PCR that tested negative for RDT and ELISA. This suggests that that they may have passed the disease, with a variable intensity (none of them required hospitalization), but didn't develop signi icant immunity, at least at the time of analysis.

Speed of immunization
It is noteworthy that between April 9 th and 21 st a total of 223 patients were tested and only 5 (2.24%) were positive. After this date, rate of positivity increased and in the remaining 298 patients tested 54 (18,12%) resulted positive.

Discussion
The study followed government guidelines which required a prescription of the test by a doctor following some kind of symptom or indication. It has been run in a hospital environment and it has addressed to HCW or patients and their relatives and close contacts. This population is considered in high risk of being infected or having been in contact with the SARS-CoV2 (or at least with a higher risk than for the normal population), and so they were supposed to have acquired a degree of immunity higher than the one observed in the general population.
In this environment, the 11,32% that developed immunity was far less than expected and much lower than what would have be considered as ideal for the herd-immunity effect [7].
One of the topics of highest public interest nowadays, is the proportion of the citizenship that has developed immunity against SARS-CoV-2. If we would extrapolate the data obtained to the general population of Spain and Barcelona we could obtain an estimate, even only partially approximated, of the numbers of people already immunized. In terms of the whole Spanish population (47.100,396), we could consider that around 5.181.044 citizens would have been in contact with the SARS-CoV-2 and would have developed signi icant immunity. This, in turn, would mean that 185.281 persons would be immunized in the metropolitan area of Barcelona.
Recently, the Spanish Ministerio de Ciencia e Innovación, the Ministerio de Sanidad, the Consejo Interterritorial sistema nacional de salud and the Instituto de salud Carlos III released the preliminary results of the irst round of the National study of sero-epidemiology of the SARS-CoV-2 infection in Spain [8]. A total of 60.983 patients were recruited. The estimated prevalence of IgG antibodies in front of the SARS-CoV-2 in Spain was 5,0% and for Barcelona of 7.1%. This data, are about half of the obtained in the present study. This can be considered normal due to the fact that one is obtained in the general population and our study is in a high-risk population.
The amount of prevalence studies is very scarce. Streeck, et al. [9] published data on 919 individuals of a small German town which was exposed to a super-spreading event. They reported a 15,5% infection rate, that was signi icantly higher than the 3.1% of icially reported cases for this community. Another study from Uppsala's university, lead by Lundkvist [10], examined 6,000 individuals and found a 7.5% of immunity rate. He studied independently 1,000 care workers and found that 23% of them had been infected, this is an infection rate much higher than the one described in the present study. Data coming from England [11] showed around a 6.78% of the people who provided blood samples tested positive for antibodies to COVID-19. Finally, Garcia-Basteiro, et al. [12], reporting data from a large reference hospital at Barcelona found a 9.3% for IgM, IgG or IgA in a sample of 578 HCW.
Folgueira, et al. [13] reported that 2085 HCW in Madrid were tested by PCR and found that 38% resulted positive for SARS-CoV-2. Tests were done during 1 st and 29 th of March 2020. No immunization data has been published. The high infection rate could be a result of the early moment in time in which the study was carried out, when no effective protective garment was provided to HCW by this time. In our series, no transmission was detected between patients and HCW, or vice versa, what probably meant that the protocol was successfully implemented. A summary of immunization results is shown in table 3.
The increasing detection rate of IgG between the irst 2 weeks and the last 2 weeks of the study could be due for two reasons: one is the delayed detection of IgG after being in contact with the SARS-CoV-2 and the other could be the fact that after releasing the isolation measures a higher degree of herd immunization was taking place. Probably, both factors had some in luence. To determine to which degree both of them contributed, a deep analysis of the epidemiology questionnaires would have to be carried out, that will be the subject of further study. In summary, RDT and ELISA probed to be effective and sensible enough to determine the extent of SARS-CoV-2 immunization in a community-based oncological center. The degree of immunization reached is nowadays far away from what can be considered desirable for a herd immunization that has been estimated to be extremely variable by country, with 69.6% in the United States and 56,1% in Iceland [7].