key: cord-0876824-6okva5w4
authors: Budziar, W.; Gembara, K.; Szymczak, A.; Jedruchniewicz, N.; Baniecki, K.; Pikies, A.; Nahorecki, A.; Hoffmann, A.; Kardas, A.; Klimek, T.; Kazmierczak, Z.; Witkiewicz, W.; Barczyk, K.; Dabrowska, K.
title: Hidden fraction of Polish population immune to SARS-CoV-2 in May 2021
date: 2021-06-25
journal: nan
DOI: 10.1101/2021.06.22.21258711
sha: 8de860dbc960aca6aea32f4dbe35991b6667a069
doc_id: 876824
cord_uid: 6okva5w4

Population immunity to SARS-CoV-2 derives from two well-defined and controlled sources: vaccinations or diagnosed and registered cases of the disease. It may however also result from asymptomatic, oligosymptomatic, or even full-blown but undiagnosed and unregistered cases from which patients recovered at home. Here we present a population screening for SARS-CoV-2 specific IgG and IgA antibodies in Polish citizens (healthy adults, N=501) who had never been positively diagnosed with or vaccinated against SARS-CoV-2. Blood samples were collected in Wrocaw (Lower Silesia) on 15th and 22nd May 2021. Sera from COVID-19 patients with a severe course (hospitalized) (N=43) or had been vaccinated (N=14) served as a positive control. The patients were tested with Microblot-Array COVID-19 IgG and IgA (quantitative) that contain specific SARS-CoV-2 antigens: NCP, RBD, Spike S2, E, ACE2, PLPro protein, as well as antigens for exclusion cross-reactivity with other coronaviruses: MERS-CoV, SARS-CoV, HCoV 229E Np, HCoV NL63 Np. Within the investigated population of healthy adults who had never been positively diagnosed with or vaccinated against SARS-CoV-2, we found that 35.5% (178 out of 501) were positive for SARS-CoV-2-specific IgG and 52.5% (263 out of 501) were positive for SARS-CoV-2-specific IgA; 21.6% of the investigated population developed virus-specific IgG or IgA while being asymptomatic. Anti-RBD IgG, which represents virus-neutralizing potential, was found in 25.6% of individuals (128 out of 501). These patients, though positive for anti-SARS-CoV-2 antibodies, cannot be identified in the public health system as convalescents due to undiagnosed infections, and they are considered unaffected by SARS-CoV-2. Their contribution to population immunity against COVID-19 should however be considered in predictions and modeling of the COVID-19 pandemic. Of note, the majority of the investigated population still lacked anti-RBD IgG protection (74.4%); thus the positive fraction is not sufficient for effective population immunity, and vaccination against COVID-19 is still of the most importance for controlling the pandemic.

COVID-19 is an acute respiratory disease caused by the novel coronavirus SARS-CoV-2, also known as 2019-nCoV. The World Health Organization (WHO) characterized COVID-19 as a pandemic on March 11 th 2020. Since then, the COVID-19 pandemic has affected most aspects of life globally, including drastic lockdowns to reduce the death toll [1] , [2] , [3] . Extraordinary efforts have been focused on developing drugs and vaccines that could help the situation. A universal anti-COVID-19 drug has still not been developed, and the major strategy for controlling the pandemic is population immunity, with the key role of SARS-CoV-2 targeting vaccines [4] .

Population immunity to SARS-CoV-2 derives from two well-defined and controlled sources:

vaccinations or diagnosed and registered cases of the disease. It may however also result from asymptomatic, oligosymptomatic, or even full-blown but undiagnosed and unregistered cases from which patients recovered at home. COVID-19 symptoms that are typical to many other flu-like and cold infections make it impossible to identify this disease without specific diagnostics. For this reason there is an unknown fraction of society that has already achieved immunity to COVID-19 but its extent is unknown. Attempts to estimate this fraction in each society is difficult, and it remains a subject of speculation, sometime extreme [5] , [6] .

Here we present the results of population screening for SARS-CoV-2 specific antibodies in Polish citizens (N=501) who had never been positively diagnosed with or vaccinated against SARS-CoV-2.

Blood samples were collected in Wrocław (Lower Silesia) on 15th and 22nd May 2021, which was shortly after the second main wave of the disease in Poland that was observed approximately between 15th February and 30th April 2021, reaching more than 35 000 diagnosed cases per day at its peak (out of almost 38 million citizens).

Overall statistics of COVID-19 for the whole country at 15th May were as follows: 11.8% of population . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (Table S1 ).

The experiments were approved by the local Commission of Bioethics of the Regional Specialist Hospital in Wrocław (approval number: KB/02/2020, policy No. COR193657). . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 25, 2021. 

Within the investigated population of healthy citizens who had never been positively diagnosed with or vaccinated against SARS-CoV-2, we found that 35.5% (178 out of 501) were positive for SARS-CoV-2-specific IgG and as many as 52.3% (262 out of 501) were positive for SARS-CoV-2-specific IgA (Table   1 ). These positive patients (with the exception of 2 individuals) did not demonstrate any crossreactivity to other coronaviruses; thus their immune response to SARS-CoV-2 is specific and it apparently results from immunization with SARS-CoV-2. Taking the high rate of SARS-CoV-2-specific IgA, more than a half of the investigated population has had a contact (or infection) with the virus. This study has revealed a significant though still not sufficient fraction of the population of people who have developed natural immunological protection against COVID-19, apparently due to an . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 25, 2021. ; https://doi.org/10.1101/2021.06.22.21258711 doi: medRxiv preprint 5 asymptomatic, oligosymptomatic, or moderate (not-requiring hospitalization) course of the disease.

Due to undiagnosed infections, they cannot be identified in the public health system as convalescents, being considered unaffected by SARS-CoV-2. This hidden fraction of immune individuals may really contribute to population immunity against COVID-19, improving the overall pandemic conditions and predictions [8] . On the other hand, this fraction seems to be insufficient for effective population immunity, since the majority of the investigated population still lacked anti-RBD IgG or IgA protection. Thus vaccination against COVID-19 is still of the utmost importance as the major tool for controlling the disease. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 25, 2021. ; https://doi.org/10.1101/2021.06.22.21258711 doi: medRxiv preprint

The coding capacity of SARS-CoV-2

WHO

Coronavirus vaccine development: from SARS and MERS to COVID-19

COVID-19 vaccines: rapid development, implications, challenges and future prospects

Towards an accurate and systematic characterisation of persistently asymptomatic infection with SARS-CoV-2

The time scale of asymptomatic transmission affects estimates of epidemic potential in the COVID-19 outbreak

ICM EPIDEMIOLOGICAL MODEL

the author/funder, who has granted medRxiv a license to display the preprint in perpetuity