Beginning December 2019 the world has been experiencing an outbreak of novel coronavirus (CoV) infection, called coronavirus disease 2019 (COVID-19). This is the third member of a family of CoVs that is associated with the development of severe acute respiratory syndrome (SARS) due to atypical pneumonia. The disease has evolved from Wuhan, China and was first reported among the visitors of local seafood market. It is likely to have a zoonotic origin as horseshoe bats are a well-known natural reservoir for a variety of CoVs that spread to humans via incidental hosts, which has not yet been identified in relation to COVID-19.1

The novel CoV was determined already on 9 January 2020 and received a name of SARS-CoV-2.2 The virus quickly spread over the globe, on 30 January 2020 the World Health Organization (WHO) declared COVID-19 a public health emergency of international concern, and already on 11 March 2020 a pandemic was announced.3 Currently, more than 5.8 million cases of COVID-19 were reported with more than 350 thousand associated deaths.4 The confirmed case is defined as a positive test for COVID-19 regardless the presence of symptoms and signs of the disease.5 Thus, identification of cases depends on testing coverage, while many countries do not test individuals with only mild symptoms.6

According to the recent meta-analysis, the most common symptoms of COVID-19 are fever (82%), cough (61%), fatigue with or without muscle aches (36%), dyspnea (26%), headache (12%), sore throat (10%), and gastrointestinal symptoms (9%).7 In China, the vast majority of COVID-19 cases are mild (81.4%), whereas 13.9% are severe and 4.7% are critical.8 In countries of European Union the proportion of severely ill patients is approximately the same and constitutes 15% of hospitalized cases.9 The increased case fatality rate (CFR) was established in older patients (≥ 60 years), males, and those who presented with severe pneumonia and comorbidities.10

As an outbreak expands in the country, more and more individuals become affected and a number of critically ill patients may increase drastically, surpassing the abilities of health care system to resist the coercive pressure. Therefore, several approaches were proposed to decrease the rate of disease spreading and to secure the capacity of health care in meeting the population demands.11 Such approaches could be divided into two broad categories–individual protection and community protection. Voluntary self-isolation, frequent hand washing, following the principles of respiratory etiquette, wearing of face masks in public places and avoidance of touching face work well on a personal level, while mass quarantine of healthy individuals, closures of schools and child care facilities, social distancing, and regular cleaning of frequently touched surfaces in public places enable community protection.12

Most countries across the globe implemented a set of protective measures with mass quarantine, social distancing, and travel restrictions being the most frequently practiced. Although it definitely had positive response, the COVID-19 pandemic is still far from its final phase and some international researchers anticipate another wave later this year.13 In this study, we aim to report on the rates of COVID-19 in the Republic of Kazakhstan, to make prognoses on cases, deaths, and recoveries through predictive modeling, and to forecast the need in professional workforce.

Overall, the crude incidence rate of COVID-19 in the country is 0.5240 with much heterogeneity between administrative units. Such, the highest incidence rate was observed in two largest cities – Nur-sultan and Almaty. It has to be noted that first patients in the country were identified in these cities and there is a high concentration of specialized medical facilities, which serve as referral centers for severely ill patients from neighboring regions. The lowest incidence rate was seen in East Kazakhstan and North Kazakhstan regions, where it constituted 0.0536 and 0.0916, respectively. The highest crude CFR was spotted in Akmola region (2.68) followed by Kostanay region (1.47) and East Kazakhstan region (1.35) (Table 2). As for the age-adjusted CFR, it was the highest in age stratum 90-99 (0.083). Eighty-eighty nine-year old males had excessive age-and-sex-adjusted CFR (0.167) and so did 90–99 year old females (0.111) (Table 3). From the beginning of COVID-19 outbreak in Kazakhstan, the vast majority of patients (87.4%) had mild disease, 11.3% had moderate disease, while severe manifestations were seen in 1.3% cases (Fig. 1).

Fig. 2 presents the results of SEIR modeling in situation when no intervention measures are applied. Such, a possible peak is 120 day after appearance of the first COVID-19 case in the country and the number of susceptible population is 7.12 million people. At the peak of COVID-19 outbreak there will be 2.038 million infected individuals, 2.5 million exposed individuals, 15.47 thousand people will die, and 156 thousand patients will require hospitalization. Fig. 3 demonstrates the changes in COVID-19 dynamics introduced by the quarantine measures. Reduction of all symptomatic patients (with mild [I1], severe [I2] and critical [I3] disease manifestation) will result in total 84.92 thousand cases at the peak (Fig. 3A). Reduction of all exposed and infected individuals will give in total 188.983 thousand cases at the peak (Fig. 3B). Reduction of all deaths will result in total 3.75 thousand cases at the peak (Fig. 3C) and reduction of all hospitalized patients (with severe and critical disease manifestation) will give in total 9.31 thousand cases at the peak (Fig. 3D).

On the next stage of our analyses we aimed to decipher the need in health care professionals at a country level depending on the fact of implementation of quarantine measures. At the peak of COVID-19 outbreak if no quarantine is applied, there will be a daily need in 12,026 ICU doctors and 58,144 ICU nurses, while introduction of quarantine may potentially reduce these numbers to 500 and 2,420, respectively. Likewise, lack of quarantine measures will necessitate the availability of 707 dialysis practitioners and 589 extracorporeal membrane oxygenation (ECMO) practitioners, while implementation of quarantine will can help to reduce these numbers to 29 and 24 practitioners, respectively. Besides, 168,576 ward nurses will be needed in the country if no intervention is applied as compared to just 7,982 nurses in case of quarantine implementation (Tables 4 and 5).

This study aimed at epidemiological elucidation of COVID-19 outbreak in the Republic of Kazakhstan and at predictive modeling of cases, deaths, and recoveries, as well as needs in professional workforce depending on implementation of quarantine measures. To the best of our knowledge, this is the first study devoted to epidemiology of COVID-19 outbreak in the Republic of Kazakhstan. The vast majority of symptomatic patients in this study have mild disease manifestations and the proportion of moderate disease is around 10%. Refusal to implement quarantine measures will result in 156 thousand hospitalized patients due to severe illness and in 15.47 thousand deaths at the peak of an outbreak. Besides, this will substantially increase the need in professional medical workforce. Still, 50% compliance with quarantine measures could potentially reduce the number of deaths up to 3.75 thousand cases and the number of hospitalized patients up to 9.31 thousand cases at the peak. Also, this may decrease the demand for medical professionals alleviating the burden placed on Kazakhstani health care system.

Having the SEIR model and parameters in hand, simulations could be carried-out for a longer time period and thus, predict the potential trends of COVID-19 outbreak both at the national and local levels. Simulation models could also evaluate the impact of different intervention scenarios.21 Other studies across the globe show good agreement between SEIR modeling and official data that fall within 95% CI. In China, the forecasted values were higher than the actual ones, which was attributed to the effectiveness of anti-epidemic measures undertaken by the country government.22 In Italy, the forecast modeling of COVID-19 outbreak showed high accordance with the real data.23

Communitywide protective measures, such as quarantine, social distancing and closure of schools and childcare facilities are broadly implemented throughout COVID-19 pandemic and Kazakhstan is not the exception. Although being effective, these measures present rather challenging issue as they might be very disruptive, and require adequate planning and community engagement.24 A recently published rapid systematic review concludes that home quarantine is not very cost-effective and should be started when pandemic just began. The authors emphasize that testing and contact tracing with rapid isolation of infected individuals–a strategy that is also undertaken in Kazakhstan–appears to be more cost-effective than quarantine.25 Apart from social and economic costs, home quarantine is associated with mental distress, as it leads to confusion, anger, and posttraumatic stress syndrome, which may have long-lasting negative effects.26

Still, quarantine measures undertaken by other countries have proven to be effective in controlling the spread of COVID-19.2122 Despite early introduction of quarantine in Kazakhstan, the outbreak continues to escalate, probably because many infected individuals have not been identified yet. This phenomenon could be explained in two different ways. First, many infected individuals remain asymptomatic and this proportion could be as high as 40%–50%.27 These individuals are not identifiable at the community level and along with those who are presymptomatic or have only mild symptoms are not likely to seek medical care. Second, individuals with known exposure, like asymptomatic/presymptomatic foreign travelers, do not readily follow the recommendations on self-isolation. Taking into consideration that inadequate compliance with quarantine leads to community transmission of SARS-CoV-2 to the susceptible individuals, this explains the continuing community spread.

As COVID-19 outbreak evolves, the scarcity of health care resources becomes a major challenge. No country in the world is prepared for rapidly increasing needs in ICU resources, including beds, equipment and professionals. In India allocation of one third of ICU beds for COVID-19 alone would result in troubling effects among other patients presenting with serious conditions requiring ICU care.28 The actual number of ICU beds available in Kazakhstan is not officially reported although the Ministry of Health made efforts to equip existing ICUs with additional mechanical ventilators and ECMO machines. However, if COVID-19 outbreak takes the negative scenario, the newly emerged patients in critical condition will completely overwhelm the health care system of Kazakhstan.

Severe cytokine activation or cytokine release syndrome (CRS) is an acute systemic inflammatory response and might be the cause of lethal outcome in otherwise healthy individuals affected by COVID-19.29 The cause of CRS is the activation of bystander immune cells and endothelial cells due to the binding of CAR T-cell receptor to its antigen. In turn, activation of bystander immune cells results in mass production of cytokines and pathophysiological cascade of subsequent events.30 Because COVID-19 patients with CRS carry worse prognosis, it is important to recognize it early in order to provide an adequate therapeutic response.31

In general, effective tackling of COVID-19 outbreak has several side aspects and improved patients satisfaction is one of them. As this outbreak caused multiple problems for the population of Kazakhstan, it is worth to maintain trust in such international organizations as the WHO32 and also in local health care providers, which became undermined over recent years.33 For this, it might prove to be useful to provide adequate information on outbreak status in a timely manner and to initiate an open dialog with general public, which could be done via social media.

The outcomes of our study could be of interest for policymakers as they help to forecast the trends of COVID-19 outbreak, the demands for professional workforce, and to estimate the consequences of quarantine measures. Our study results based on combination of official data on COVID-19 outbreak in Kazakhstan and SEIR modeling, suggest that 50% compliance with quarantine measures could potentially reduce the number of cases. According to available international reports, introduction of quarantine may provide beneficial effects. In reality, Kazakhstan initiated quarantine very early and combined it with other community protection measures, including closure of all educational establishments, restriction of travels and cleaning with disinfection in public places. Thus, this model is likely to show exaggerated results and the real situation can be more optimistic if the country government will not cease the interventions preliminary. We hope that this simulation can be useful for managing COVID-19 outbreak in Kazakhstan, as well as in other countries that are still at an early stage of COVID-19 epidemic.