FEATURES OF THE CLINICAL COURSE OF CORONAVIRUS INFECTION IN MEDICAL STAFF DURING PERIODS OF DOMINANCE OF VARIOUS GENOVARIANS

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Introduction

The new coronavirus infection (NCI, (COVID–19), occurring with severe acute respiratory syndrome, caused by the SARS-CoV-2 virus has led to the occurrence of the disease in more than 750 million people worldwide, including at least 2% fatalities, and has been designated as a pandemic. Despite the fact that the international emergency regime was lifted in May 2023, diseases associated with SARS-COV-2 continue to be registered at present, as well as its consequences [1]. Therefore, COVID–19 does not lose its relevance as a problem in the Russian Federation (RF) and in various countries of the world, not only from the point of view of healthcare, but also in terms of the impact on the country's economy.
The peculiarity of this infection was its rapid spread, high morbidity and mortality rates, the absence at the initial stage of antiviral drugs with proven clinical efficacy for specific treatment, and a clear understanding of the immune response to both the infection itself and vaccination [2, 3].
One of the most vulnerable professional categories in the population, both during the pandemic period and after its cancellation, were healthcare workers who have a high professional risk due to exposure to a biological factor (SARS-CoV-2), prolonged contact with a source of infection, and the fact of deterioration in health due to overexertion due to the duration and intensity of work, as well as the presence of various stressful situations in the workplace [4].
A huge scientific potential is aimed at studying the NCI, however, questions still remain regarding the characteristics of the clinical process, including within individual professional cohorts - among healthcare workers in medical institutions.
It seems relevant to study the characteristics of the course of NCI during different periods of increased incidence.
The purpose of the study is to study the course of the acute period of infection caused by SARS-CoV-2 in healthcare workers in comparison with individuals not engaged in medical activities.
Materials and methods
To study the frequency of features of COVID-19 disease episodes in healthcare workers and other individuals, professions, an Internet resource (testograf.ru) was used, on the basis of which anonymous online questionnaires were posted. The questionnaire included three blocks of questions: information about the patient (gender, age, height, weight, presence of concomitant diseases); data on the transferred NCI and vaccination (presence of vaccination, name of the vaccine, dates of vaccination and onset of the disease, clinical form of NCI, its severity, instrumental examinations performed indicating the level of lung damage, the need for oxygen support and hospitalization); data on the recovery period of NCI (presence of complaints, period of occurrence and their duration). The survey involved employees of Rospotrebnadzor, carrying out both therapeutic and preventive activities, and persons who are not related to medical workers. A one-stage online study was conducted from June to September 2022.
Analysis of the dominant genovariant of NCI in the Russian Federation was obtained on the basis of data posted on https://nextstrain.org.
Criteria for inclusion in the study: age from 18 years old; history of laboratory-confirmed NCI. Exclusion criteria for the study: filling out an online questionnaire for less than 5 minutes; persons with no history of NCI.
A total of 39,655 people followed the link and answered the questions. According to the exclusion criteria, 22,535 persons who had COVID-19 were included in the analysis. The overwhelming majority of persons included in the analysis of the course of NCI were women (88% of health workers and 81.1% among persons of other professions). Also, the majority of respondents were young people (according to WHO, up to 44 years old) - 62.6% and 67.2%, respectively. At the age of 45-59 years, 37.4% of health workers and 33.8% of persons of other professions accounted for, for persons over 60 years old - 0.01% and 0.02%, respectively.
Chronic diseases were registered in 3,780 (28.6%) of healthcare workers and 2588 (27.8%), weight change in the form of obesity (calculated by body mass index) 2126 (16.1%) of healthcare workers and 1431 (15.3%) among people of other professions.
The analysis of the clinical course was carried out depending on the period of circulation of various strains and professional affiliation. During the period of circulation of the "Wuhan" genovariant (B.1.1. (20 B nextstrain.)) 7944 people were infected, the genovariant "Delta" (B.617.2 (21A, 21 I, 21J. nextstrain.)) 8069, with the dominance of the genovariant "Omicron" (B.1.1.529 (21K, 21 L, 21M. nextstrain.)) 6522 people.

Statistical analysis
All statistical analysis was conducted using Statistica 10.0. To describe quantitative data with a normal distribution, the arithmetic mean (M) and standard deviation (SD) were used. When describing qualitative data, frequencies and proportions (in %) in each sample were used. Comparison of two independent groups of nominal data was performed using the Pearson chi-square (χ2) test.

 

Results
The preservation of the predominant clinical variant for the three-year period from 2020-2022 in the form of acute respiratory viral infections (60.4%) was noted, pneumonia accounted for 21.7%, other forms accounted for 12%, and the asymptomatic variant accounted for 5.9%. Depending on the structure of the dominance of the genovariant, the NCI was established by the peculiarity of the clinical picture. Thus, for the “Wuhan” genovariant, in comparison with the disease caused by the “Delta” genovariant of SARS-CoV-2, a more frequent asymptomatic course was recorded (6.3% versus 5.5%, p = 0.0317) and a course in a different form (with gastrointestinal tract damage, anosmia, cardiovascular pathology, their combination) (27.5% versus 5.1%, p < 0.0001), and a rarer variant of acute respiratory viral infection (43.9% during the period of circulation of the “Wuhan” genovariant and 60.3% during the period of dominance of “Delta”, p < 0.0001) and more frequent pneumonia (22.3% and 29.7%, respectively, p < 0.0001), and the presence of complications in the acute period (16.1% versus 2.5%, respectively, p < 0.0001). It was determined that the "Wuhan" genovariant, in comparison with the disease caused by the "Omicron" genovariant of SARS-CoV-2, is characterized by a more frequent development of the clinical variant "pneumonia" and another form of the disease (22.3% during the period of circulation of the "Wuhan" genovariant versus 11.9% during the period of dominance of "Omicron", p < 0.0001). The disease more often acquired a complicated course (16.1% versus 2.0%, respectively, p < 0.0001) and patients needed oxygen support (8.3% versus 1.2%, respectively, p < 0.0001). Along with this, the predominant variant in the disease caused by the "Omicron" genovariant was ARVI (43.9% versus 80.4%, respectively, p < 0.0001). The clinical forms of the disease caused by the "Delta" genovariant in comparison with the "Omicron" genovariant were characterized by a more frequent variant of lower respiratory tract damage in the form of pneumonia (29.1% in the "Delta" dominance period and 11.9% in the "Omicron" dominance period, p < 0.0001), the presence of another form (5.1% versus 1.9%, respectively, p < 0.0001), and the need for oxygen support (7.7% versus 1.1%, respectively, p < 0.0001). In the case of the disease caused by the "Omicron" genovariant, a mild course was more often observed, and the most frequent clinical variant was acute respiratory viral infection (60.3% versus 80.4%, respectively, p < 0.0001). The impact of vaccination on clinical manifestations of the disease
The obtained data indicate the effectiveness of immunoprophylaxis using domestically developed vaccines during the period of circulation of the "Wuhan" genovariant. Thus, regardless of profession, the disease was more severe in unvaccinated individuals: pneumonia was recorded more often in 22.5% compared to vaccinated individuals - 18.4%, p < 0.05, with a higher percentage of lung parenchyma involvement (CT 2 in unvaccinated individuals occurred in 83.3% compared to vaccinated individuals - 69.5%, p < 0.05), complicated course in the form of secondary infection (pneumothorax, pleurisy, myocarditis, pericarditis, endocarditis, aseptic necrosis of the joint, sinusitis, tonsillitis, otitis, conjunctivitis, occurrence of gastropathology (pancreatitis, hepatitis) or sepsis, thrombosis was also observed more often in unvaccinated individuals (16.3% and 15% versus 11.5%, respectively, p < 0.05) and a more frequent need for oxygen support. (8.4% versus 5.5%, respectively, p<0.05).
During the period of dominance of the "Delta" genovariant, it was noted that vaccination continued to reduce the risk of pneumonia and the need for oxygen support: both in health workers - signs of viral inflammation in the lungs (40.2% among unvaccinated versus 27.6% among vaccinated, p<0.0001) and the need for oxygen support (11.4% versus 7.4%, p<0.0001), and in people of other professions (15.5% versus 11.1%, p=0.0563) and the need for oxygen support (1.9% versus 0.8%, p=0.1046). However, there were no differences in the incidence of complications in the acute period, as well as in the

and in the severity of the degree of changes in the lungs of vaccinated and unvaccinated individuals during this period, no changes were detected, which indicates a decrease in the effectiveness of the vaccines used during the period of circulation of the "Delta" genovariant.
The period of dominance of the "Omicron" genovariant was marked by a milder course, which manifested itself in the overwhelming majority in the form of acute respiratory viral infections (80.3%), and only one in ten had pneumonia, a low need for oxygen support (1.1%) and a rare occurrence of complications (2.0%). The lack of effectiveness of the vaccination was clearly demonstrated during this period - it was not possible to identify statistically significant differences between vaccinated and unvaccinated individuals. A comparative analysis of healthcare workers and people of other professions during the period of dominance of the "Wuhan" genovariant revealed that, despite the fact that the frequency of acute respiratory viral infections in the two groups did not differ, pneumonia was registered statistically significantly more often among healthcare workers (23.2% versus 20.9%, p < 0.0001), as well as the need for oxygen support (9.4% versus 6.7%, p < 0.0001) and the frequency of complications in the acute period (17.1% versus 14.5%, p = 0.0019). When comparing the degree of changes in the lungs, it was also found that the number of people with a larger area of ​​changes in the lungs among healthcare workers was higher (on CT 2 and higher, healthcare workers accounted for 93.5% versus 75.3% of all registered pneumonias, p < 0.0001) (see Table 1). A comparative analysis of healthcare workers and people of other professions during the period of dominance of the "Delta" genovariant revealed a statistical difference in the frequency of the clinical variant of ARVI (58.9% in healthcare workers and 62.3% in people of other professions, p = 0.0021), the frequency of inflammation in the lungs (30.14% and 27.6%, respectively, p = 0.0149), ARDS was isolated and registered only in a vaccinated healthcare worker. The asymptomatic form accounted for 5.5%, anosmia - 3.6% (among healthcare workers 4% versus 3% of people of other professions, p = 0.0174), gastrointestinal pathology - 1.4%. Several cases occurred in other forms - only cardiovascular pathology (0.05%) and central nervous system pathology (0.37%). The need for oxygen support was registered in 7.7% (8.2% of health workers and 6.9% of people of other professions, p=0.0307) (see Table 1).
In a comparative analysis of health workers and people of other professions during the period of dominance of the "Omicron" genovariant, only a trend in the need for oxygen support was revealed (1.3% of health workers and 0.9% of people of other professions, p=0.1367). There were no statistically significant differences in the frequency of clinical forms: ARVI was found in 80.0% of healthcare workers and 80.8% of people of other professions, p = 0.9066, the number of pneumonias reached 11.9% (12.3% in healthcare workers and 11.5% in people of other professions, p = 0.3259), ARDS was isolated and was registered only in a vaccinated healthcare worker (see Table 1).

Discussion

According to the data obtained, it was determined that the predominant clinical variant for the three-year period from 2020-2022 was ARVI (60.4%), regardless of profession, pneumonia accounted for 21.7%, other forms - 12%, and the asymptomatic variant - 5.9%. The data obtained are generally in line with previously published data [3].

During the period from 2020 to 2022, SARS-CoV-2 continued to evolve and mutate, resulting in the emergence of new subvariants, including recombinant ones, which consistently transformed into globally dominant forms. The virus is characterized as unique in its evolutionary characteristics compared to other respiratory viruses [5].
According to the data obtained, the clinical profile and manifestations of the disease varied depending on the strain, but no fundamental and significant differences in the clinical course of the disease were identified. Despite the similarity of the clinical picture, the circulation period of the Delta genovariant is marked by frequent lesions of the lower respiratory tract, and the Omicron genovariant is characterized by a mild course. Similar data were obtained in a number of studies [6]. A feature of the circulation period of the Omicron genovariant was a milder clinical course of COVID-19 and low mortality compared to previous waves of the pandemic [6, 7]. Our study obtained unidirectional data. The vast majority of patients during the period of circulation of the Omicron genovariant received treatment at the outpatient stage. During the period of circulation of this variant of the virus, severe course of the disease and the need for hospitalization, including in the intensive care unit, with the need for artificial ventilation of the lungs, were extremely rare; a decrease in mortality was also noted compared to infection with the Delta strain. These differences in the course of the disease in patients caused by the Omicron strain and patients with infection caused by the Delta strain are consistent with a reduction in the proportion of all cases of SARS-CoV-2 infection that led to severe clinical consequences. According to the results of previous studies, the risk of hospitalization due to infection with the omicron strain was reduced by 20-80% [8]. In a large-scaleThe inclusion of individuals using social networks presented data on the dynamic characteristics and joint manifestation of symptoms of the COVID-19 pandemic, obtained on the basis of the analysis of data of 471,553,966 respondents who had recovered from COVID-19, for the period from February 1, 2020 to April 30, 2022. The data allowed us to draw the following conclusions: as the pandemic developed, the frequency of symptoms changed: from typical respiratory symptoms at an early stage to a change to an increase in the number of people with musculoskeletal complaints and complaints from the nervous system at later stages. The authors found differences in symptoms during the periods of spread of the Delta and Omicron strains. During the period of predominant circulation of the "Omicron" genovariant, fewer severe symptoms (coma and shortness of breath) and more symptoms similar to acute respiratory viral infections (sore throat and nasal congestion), fewer typical symptoms characteristic of COVID-19 (anosmia and changes in taste sensations) were recorded than during the period of spread of "Delta" (for all indicators, p < 0.001) [9]. According to the Federal Budgetary Scientific Institution "Central Research Institute of Epidemiology" of Rospotrebnadzor in the Russian Federation (RF), in 2022, during the period of predominant circulation of the "Omicron" genovariant, mild and moderate forms of severity prevailed - 69.1% and 29.8%, respectively. A decrease in the severe course of the disease was noted from 2.5% in 2021 to 1.1% in 2022, and the frequency of pneumonia registration from 22% in 2021 to 4.6% in 2022 of all registered cases of COVID-19 [3]. In our study, in the period 2020-2022, healthcare workers were characterized by a more frequent registration of pneumonia (22.6% versus 20.5%, p = 0.0002) and the need for oxygen support (6.7% and 5.1% p < 0.0001), the presence of a complicated course (7.3% versus 6.9%, p = 0.2506). Conflicting data have been published in the literature. Thus, in a German study, the frequency of severe NCI among doctors was twice as high as among other workers (8.1% versus 4.1%). The authors associated this problem with less frequent testing even in the presence of mild forms [10]. Conflicting data have been published by Italian researchers. Thus, in one publication, the authors reported that the cumulative incidence of SARS-CoV-2 among healthcare workers (n = 1447) was 11.33% (95% CI: 9.72–13.21). In most cases, the disease was mild, hospitalization was required only in 5.5% of cases, and there were no fatal cases. Most of those infected (90.2%) had symptoms at the first stage, the most common of which was fever (69.5%), followed by asthenia (44.5%), ageusia (36%), and anosmia (40%). On average, healthcare workers with a positive test result were absent from work for 18 days, and the average time until receiving a negative swab result was 16 days [11]. Another publication noted a high level of infection and mortality among healthcare workers, partly due to a lack of adequate PPE (Ranney M. L. et al., 2020) [12]. According to Saudi Arabia, the incidence of healthcare workers by the end of 2020 was 10%. Moreover, the most vulnerable category was nurses (36%). Healthcare workers who became infected in healthcare institutions more often became ill from other healthcare workers (63%) [13]. According to the data of Bukhtiyarov I. V. and co-authors (2025), obtained on the basis of an analysis of anonymized information from the network of healthcare institutions of JSC RZhD-Medicine (form C-51), it was established that among healthcare workers for the period from 01.01.2020 to 31.12.2022, out of 25,099 men and 134,208 women who fell ill, 40 men and 73 women died. In the male cohort, the risk of dying from COVID-19 was significantly higher among healthcare workers than the population (ORR=1.86; 95% CI 1.05–3.31). The indicator was formed due to the high risk in the professional group of doctors (ORR=1.96; 95% CI 1.06–3.62). Among female doctors, the ORR=1.37, but the differences are insignificant (95% CI 0.77–2.44). In other professional groups of the female cohort, the ORR of death was significantly lower than the population one [14].
Despite the fact that studies have shown good protection against severe COVID-19 in vaccinated individuals in the form of a reduced risk of death, even in the case of prevalence of the Delta and Omicron strains in the population [15–18], a number of studies indicate a decrease in effectiveness during periods of emergence of mutant strains of the virus [15–17]. Our data indicate a gradual decrease in the effectiveness of vaccination during the period of genovariant change and are identical to a number of published data [19-20]. Thus, it has been shown that the serum of recovering people who had previously recovered from COVID-19 showed weaker neutralizing activity against the Omicron strain compared to the Delta strain (and earlier strains) [15]. Given the alarming frequency of the emergence of new SARS-CoV-2 strains, the effectiveness of existing vaccines remains questionable [16]. A study has been published in the literature indicating a decrease in the effectiveness of vaccination due to the loss of epitopes in new strains and their predicted departure from antibodies to SARS-CoV-2 produced by  [17]. In this regard, both compliance with anti-epidemic measures and factors of non-specific resistance of the body are of particular relevance.
Conclusion
The past COVID-19 pandemic, characterized by rapid mutation of the virus and change of genovariants, was a challenge for practical and scientific medicine. Despite the huge number of publications, studies devoted to the SARS-CoV-2 virus and clinical manifestations of COVID-19, based on data from hospitals or outpatient clinics, taking into account clinical symptoms and variants of the course of infection, the data obtained may be biased due to the high proportion of both asymptomatic and low-symptom manifestations of the virus, which are not always recorded. A feature of our study was the presentation of data using an Internet resource, which allows us to most fully reflect the objective reality in the framework of morbidity among health workers. The study revealed the features of the clinical course among health care workers.

About the authors

Evgeniya Medvedeva

Department of Pediatric Infectious Diseases, Federal State Budgetary Educational Institution of Higher Professional Education RMANPO of the Ministry of Health of the Russian Federation Russia.

Author for correspondence.
Email: evgeniya0103med@yandex.ru
ORCID iD: 0000-0001-7786-3777
SPIN-code: 7164-3821

Department assistant

Chief specialist

Russian Federation, 125993, Russian Federation, Moscow, Barrikadnaya St., 2/1, building

German Gennadievich Maryin

Federal State Budgetary Educational Institution of Continuing Professional Education Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow. Russian Federation.

Email: ger-marin@yandex.ru
ORCID iD: 0000-0003-2179-8421
SPIN-code: 4205-1746

Doctor of Medical Sciences, Professor of the Department of Epidemiology of the Federal State Budgetary Educational Institution of Continuous Professional Education Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation.

Russian Federation, 125993, Russian Federation, Moscow, Barrikadnaya st., 2/1, building 1.

Antonina A. Ploskireva

Central Research Institute of Epidemiology

Email: antoninna@mail.ru
ORCID iD: 0000-0002-3612-1889

MD, Professor, Deputy Director for Clinical Work

Russian Federation, Moscow

Tatyana A. Chebotareva

Russian Medical Academy of Continuous Professional Education

Email: t_sheina@mail.ru
ORCID iD: 0000-0002-6607-3793
SPIN-code: 1053-8790

 MD, Professor, Head of the Department of Pediatric Infectious Diseases, Federal State Budgetary Educational Institution of Higher Professional Education, Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation, Honored Doctor of the Russian Federation

Russian Federation, Moscow

Alexander N. Letyushev

Federal Service for Surveillance on Consumer Rights Protection and Human Well-Being

Email: fguz@mossanepid.ru
ORCID iD: 0000-0002-4185-9829

Саnd. Med. Sci., Deputy Head

Russian Federation, Moscow

Vladimir A. Loginov

Podolsk Regional Clinical Hospital

Email: maleus.manus@gmail.com
ORCID iD: 0000-0001-7176-4022
SPIN-code: 2779-7530

Саnd. Med. Sci., Doctor of the Highest Qualification Category; Head of the Gastroenterology Center

Russian Federation, Podolsk

References

Supplementary files