SARS-CoV-2 molecular evolution and human immune response to infection: Doctoral thesis in medical sciences: 313.02. Medical microbiology, virology

Abstract

Actuality and importance of the researched problem The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and quickly spread globally, causing the COVID-19 pandemic [1]. As of March 11th, 2023, the pandemic has caused over 760.4 million confirmed cases and 6,8 million deaths globally [2]. Since the outbreak, the virus has undergone rapid evolution, leading to the emergence of several variants of concern (VOCs) that are more transmissible, virulent, and potentially resistant to immunity induced by natural infection or vaccination. Up to date, the following VOCs were detected: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2) and omicron (B.1.1.529, BA.2, BA.4, BA.5) [3,4], the first variants have been de-escalated as no more circulating. Understanding the molecular evolution of SARS-CoV-2 and the human immune response to infection is critical for developing effective strategies to combat the virus and protect public health [5,6]. Genomic sequencing allows real-time monitoring of viral transmission dynamics by tracking sequences that aggregate together in clusters and correlating them with clinical and epidemiological data [7,8]. These data are necessary to timely inform public health about the emergence of VOCs’ allowing an efficacious response [9]. Although whole-genome SARS-CoV2 sequencing has reached an astonishing number of records, the geographic coverage is still not homogeneous, with large areas reporting only a few sequences. It is, therefore, critical to uniform sequencing coverage to monitor the molecular evolution of the virus worldwide. The Republic of Moldova is a small Eastern European country with a population of 3.6 million [10]. The Republic of Moldova is facing a severe emigration process. Some estimate that around one million Moldovan citizens are working abroad [11], including areas of early extensive transmission of SARS-CoV-2 in Europe. On the 7th of March 2020, a 48-year-old woman who returned from Italy was the first recorded case of SARS-CoV-2 confirmed by real-time reversetranscriptase polymerase chain reaction (RT PCR) [10,12]. In one month, the number of infected people increased to 965, with 854 cases transmitted locally and 111 imported [10,13]. Up to date (July 17, 2023), there have been 620.758 confirmed COVID-19 cases and 12.124 deaths [14]. Due to the lack of sequencing facilities in the Country, the initial strategy adopted was to partner with international institutions such as the International Centre for Genetic Engineering and Biotechnology (ICGEB) and the Charité Universitätsmedizin in Berlin, Germany [7]. Subsequently, the national diagnostic capacities of SARS-CoV-2 were expanded, and in January 2022, the National Agency for Public Health sequenced the first SARS-CoV-2 genome [15].[...]