key: cord-0735712-8vnw5e6y
authors: Smagul, Manar; Esmagambetova, Aizhan; Nusupbaeva, Gauhar; Kirpicheva, Ulyana; Kasabekova, Lena; Nukenova, Gauhar; Saliev, Timur; Fakhradiyev, Ildar; Tanabayeva, Shynar; Zhussupov, Baurzhan
title: Sero‐prevalence of SARS‐CoV‐2 in certain cities of Kazakhstan
date: 2022-03-15
journal: Health Sci Rep
DOI: 10.1002/hsr2.562
sha: 594d0c7920c8f7249113ce96a04ceba3c98634f9
doc_id: 735712
cord_uid: 8vnw5e6y

BACKGROUND AND AIMS: Seroprevalence studies are needed to determine the cumulative prevalence of SARS‐CoV‐2 infection and to develop pandemic mitigation strategies. Despite the constant monitoring and surveillance, the true level of infection in the population of Kazakhstan remains unknown. The aim of this study was to determine the sero‐prevalence of SARS‐CoV‐2 in the main cities of Kazakhstan. METHODS: The research was conducted as a cluster‐randomized cross‐sectional national household study in three cities of Kazakhstan. The study covered the period: from October 24, 2020, to January 11, 2021. A total of 5739 people took part in the study. All participants agreed to be tested for antibodies to IgM/IgG. Demographic characteristics were analyzed. The presence of symptoms of respiratory diseases and the results of polymerase chain reaction (PCR) testing were determined. The antibodies to the SARS‐CoV‐2 virus were detected using the method of enzyme‐linked immunosorbent assay (ELISA). RESULTS: There was significant geographic variability with a higher prevalence of IgG/IgM antibodies to SARS‐CoV‐2 in Almaty 57.0%, in Oskemen 60.7% than in Kostanay 39.4%. There were no significant differences in prevalence between men and women (p ≥ 0.05). In Almaty, only 19% of participants with antibodies reported the presence of respiratory symptoms during a pandemic. At the same time, the percentage of patients with antibodies who had respiratory symptoms was 36% in Oskemen and 27% in Kostanay. CONCLUSION: The findings indicate that despite reasonable level of seroprevalence, the country has not yet reached the baseline minimum of herd immunity scores. The prevalence estimates for asymptomatic or subclinical forms of the disease ranged from 64% to 81%. Thus, given that almost half of the population of Kazakhstan remains vulnerable, the importance of preventive strategies such as social distancing, the use of medical masks, and vaccination to protect the population from the transmission of SARS‐CoV‐2 is highly critical.

In December 2019, an outbreak of a new coronavirus infection caused by the SARS-CoV-2 virus was reported in the Chinese province of Wuhan. 1 The first case outside China was reported on January 13, 2020, in Thailand. 2 Due to the alarming spread of the infection and the severity of the consequences, the World Health Organization (WHO) declared the COVID-19 outbreak as a pandemic on March 11, 2020. 3 In Kazakhstan, the first cases of COVID-19 infection were registered on March 13, 2020, among persons arrived from Germany. 4 The first cases of coronavirus infection in the communities were recorded on March 28. 5 As of January 16, 2021, 167, 118 cases of COVID-19 and 2397 deaths (COVID-19 related) were registered in Kazakhstan. 6 Since the beginning of the pandemic, quarantine and isolation procedures have been implemented around the world. The tough control measures have been also taken in Kazakhstan, including school closures, social distancing, strict border controls, restrictions on store opening hours, and so on. 7 As a matter of fact, epidemiological surveillance of confirmed cases of COVID-19 covers only a fraction of all registered cases of infection, since the clinical manifestations of SARS-CoV-2 can range from asymptomatic carrier age to a serious illness with еру lethal outcome. 8 Conducting a sero-epidemiological survey on a specific population could help to quantify the proportion of the people that have antibodies against SARS-CoV-2. 9 Thus, a sero-epidemiological study can provide information on the number of people exposed to coronavirus infection. The antibodies are a marker of total or partial immunity, but they can also provide information about the percentage of the population that remains susceptible to the virus. 8 To date, a few epidemiological studies of COVID-19 cases among the adult and child population have been carried out on the territory of Kazakhstan since the beginning of the pandemic. 10, 11 However, no studies have been conducted to determine the level of sero-prevalence in the local population yet. Therefore, the aim of this study was to determine the sero-prevalence of SARS-CoV-2 in the main cities of Kazakhstan. 

For the study (September 2020), the following three cities (Figure 1) with different levels of morbidity were selected: Almaty (cumulative incidence rate 720.8 per 100 thousand population), Oskemen (642.1), and Kostanay (709.0). The city choice was dictated by the geographical location (south, east, and north, respectively). At the end of the study (January 2021), high cumulative incidence rates were detected in Kostanay (2021.2 per 100 thousand population) and Oskemen (1637.4). The low levels of incidence rates were observed in Almaty city (1108.3).

Household inclusion criteria: one or more people living independently or together in a residential building with a common kitchen or common access to a living space. 

The study samples were formed by using the clusters. The clusters were arranged on the sites of medical organizations providing primary health care (PHC) for the local population. The study was conducted in the period from October 24 to January 11, 2021.

The demographic characteristics of the study participants were determined, such as gender and age. In addition, the presence of symptoms of respiratory diseases since March 2020 and results of polymerase chain reaction (PCR) testing was also analyzed.

Laboratory studies were carried out by enzyme-linked immunosorbent assay (ELISA) 12 in the reference laboratory (RL) for the control of viral infections "National Centre for Public Health" in Almaty (branch of the "Scientific and Practical Centre for Sanitary and Epidemiological Expertise and Monitoring"). The laboratory is part of the global network for the diagnosis of poliomyelitis, measles, rubella, influenza and is the WHO regional RL for these diseases. 

For the statistical processing of the data, the R program was used. To obtain an estimate of the prevalence of antibodies in cities, the data were weighted taking into account the sex and age distribution of the urban population of Kazakhstan. Ninety-five percent confidence intervals (CIs) were calculated. The statistical significance of differences in prevalence between groups was determined using the χ 2 test. The ɸ coefficient was used to measure the association between two dichotomous variables.

Characteristics of the study sample presented in Table 1 

The overall prevalence of antibodies to the SARS-CoV-2 virus weighted by gender and age was significantly different (p < 0.001) in three cities: 57.0% (95% CI = 56.9%-59.8%) in Almaty, 60.7% (95% CI = 57.9%-65.5%) in Oskemen and 39.4% (95% CI = 35.8%-43.7%) in Kostanay.

The prevalence in Almaty and Oskemen did not differ significantly but was higher than in Kostanay (p ≤ 0.05). The prevalence of antibodies to SARS-CoV-2 in different subgroups are presented in Table 1 .

Analysis of the prevalence of antibodies to the SARS-CoV-2 virus by sex showed that the proportion of positive results among males was higher in all cities, but the difference was not statistically significant (p ≥ 0.05).

F I G U R E 1 The prevalence of antibodies to the SARS-CoV-2 virus, depending on the region of localization of the study participants in Kazakhstan SMAGUL ET AL. | 3 of 8

By age group, the prevalence of antibodies in Almaty ranged from 45.7% (95% CI = 41.2%-50.2%) among people over 70 years old to 63.0% (95% CI = 59.2%-66.7%) at the age of 50-59 years. These findings indicate that there was less prevalence in older age groups.

In Oskemen and Kostanay cities, no significant relationship was found between age and prevalence.

The prevalence of antibodies to SARS-CoV-2, depending on the age category, is presented in Table 3 . 

The serological prevalence of antibodies specific to SARS-CoV-2 was However, it is difficult to say that the infection was less common among children and adolescents than among adults, because of the difference in immunological reactions of children from adults. 13 These results are consistent with the fact that infected children are less likely to develop the severe disease than adults. 10 The statistical significance of differences in antibody prevalence We observed the high prevalence of antibodies among participants who did not experience respiratory symptoms. In the cities included in the study, it ranges from 40% to 57%.

Of particular interest is the analysis of the prevalence of symptoms depending on the test result for antibodies to SARS-CoV-2, since it allows one to assess the proportion of asymptomatic infection and subclinical course of the disease. The prevalence estimate for asymptomatic new coronavirus infection in three cities ranged from 64% to 81%. The rapid transmission of SARS-CoV-2 infection and the high prevalence of asymptomatic carriers suggest that a universal testing approach rather than a symptom-based approach is needed to prevent the spread of infection to vulnerable populations from asymptomatic carriers. 16 The prevalence of antibodies among "contacted" population was higher than among people who were not contacted COVID-19 patients in two cities Almaty and

Oskemen. In Kostanay city, no significant difference in prevalence was found between the two categories.

A statistically significant relationship between the prevalence of antibodies among people who have been in contact and who have not been in contact with known cases of COVID-19 was determined only in Almaty.

Previous sero-prevalence studies undoubtedly differ in terms of the population involved, the sampling strategy and laboratory tests chosen, the study design and methodology, and the variable circulation of SARS-CoV-2 in the populations involved. 17 For example, the prevalence of antibodies to SARS-CoV-2 in Kazakhstan is significantly higher than in European and Asian countries such as Iran (17.1%), 18 Sweden (15.0%), 19 Chile (10.7%), 19 Switzerland (6.4%), 20 Italy (7.27%), 19 South Korea (7.6%), 21 Spain (5.0%), 8 and United States (4.4%). 19 The high prevalence of antibodies in Kazakhstan might be explained by the fact that studies in these countries were carried out earlier than ours (April to June 2020). In the cities of Kazakhstan, the peak incidence of COVID-19 was observed in June to July, while the study was conducted from the end of October 2020 to January 2021. Given that the duration of antibody retention after infection varies individually and tends to decrease over time (40% of asymptomatic cases will become seronegative after 2 months), 26 the vaccination campaign among the population plays a key role in ending the epidemic. With SARS-CoV-2 vaccination becoming more widely available globally, the use of serology as a pandemic control tool could transform from a diagnostic modality to a criterion of vaccination efficacy. 27 Despite the high prevalence of antibodies in the study (from 39.7% to 61.7%), this is not enough to stop the COVID-19 pandemic.

With a baseline reproductive number of R0 = 3, two-thirds of the population must be immune to infection to stabilize its spread.

However, the acquired immunity (after an illness or vaccination) does not guarantee complete protection against infection. Moreover, variants that cause impaired immunity (α and especially delta) are able to overcome the immune defence, and they have a higher infectivity.

Thus, it is impossible to achieve complete elimination of the virus at this stage. It is evident that the SARS-CoV-2 pandemic will continue, 28 but large-scale vaccination can mitigate its effects.

The prevalence of antibodies to the SARS-CoV-2 virus in the three Kazakhstan cities selected for the study ranged from 39.7% to 61.7%.

The results indicate that despite reasonable seroprevalence, the country has not yet reached the baseline minimum of herd immunity scores. The prevalence estimates for asymptomatic or subclinical forms of the disease ranged from 64% to 81%. Thus, given that 

This study has a few limitations. First, despite an important role in the pathogenesis of COVID-19, indicators of secretory IgA, as well as IgM and IgG were not included in the analysis. Second, all household members aged 5 years and older were included in the study that creates an additional cluster effect (caused by high infectivity of the SARS-CoV-2). The prevalence of antibodies to the virus in households was homogeneous. Therefore, if any member of the family became ill, the rest of the family was highly likely to become infected.

Third, the study determined the prevalence of common antibodies to the SARS-CoV-2 virus, but not only neutralizing antibodies. Although the presence of common antibodies is highly correlated with the presence of neutralizing antibodies, the prevalence of common antibodies may not coincide with the prevalence of neutralizing antibodies. Thus, the sero-prevalence results cannot directly characterize the proportion of the population immune to COVID-19. Finally, some of the selected households or participants were not available to participate in the study, which could potentially be a source of selection bias.

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The authors are grateful to the World Health Organization for technical and financial support and the provision of serological tests for the study. 

The authors declare no conflicts of interest. 

All relevant data are included in the article.

http://orcid.org/0000-0003-0528-3874