SARS-CoV-2 molecular evolution and human immune response to infection: Summary of 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]. March 11th, 2023, the pandemic has caused over 760.4 million confirmed casesand6,8million 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]. On 7 March 2020, the first confirmed case of SARS-CoV-2 infection was registered in the Republic of Moldova [10,11]. In one month, the number of infected people increasedto965,with 854 cases transmitted locally and 111 imported [11,12]. Up to date (July 17, 2023), there have been 620.758 confirmed COVID-19 cases and 12.124 deaths [13]. It is indeed tragic that the COVID-19 pandemic has caused so much loss of life worldwide, including in the Republic of Moldova. The development of vaccines and antiviral drugs, as well as the use of human-neutralising antibodies (nAbs) are all essential strategies to combat the virus [14]. In March 2021, 2000 doses of Sinopharm vaccine were donated to the Republic of Moldova, which were administered exclusively to students and professors at the Nicolae Testemitanu University of Medicine and Pharmacy [15]. While vaccination campaigns are important in preventing the spread of COVID-19,effective therapeutic solutions are still needed [16] to treat people who have already been infected with the virus, especially those at higher risk of developing severe disease. Preliminary results from clinical trials have shown that the use of human neutralising antibodies targeting the ACE2 receptor binding domain (RBD) of SARS-CoV-2 can reduce disease severity and accelerate recovery in patients with COVID-19 [17,18]. Terapia cu plasmă convalescentă s-a dovedit a fi promițătoare în tratamentul pacienților cu COVID-19în stare critică [19]. The FDA has also recommended that convalescent plasma with a neutralising antibody titre greater than 1:160 be used for therapeutic transfusions [20]. However, theuseofconvalescent plasma is limited by the availability of donors with high levels of neutralising antibodies. Serological tests that detect neutralising antibodies to SARS-CoV-2 are essential for monitoring the effectiveness of vaccines and identifying people who may still be susceptible to the virus. Such tests can also be used to identify people who may have developed neutralising antibodies after being infected with SARS-CoV-2. [...]