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. 2025 Mar 27;17(4):481.
doi: 10.3390/v17040481.

The Clinical and Laboratory Landscape of COVID-19 During the Initial Period of the Pandemic and at the Beginning of the Omicron Era

Yulia A Desheva  1   2 , Tamara N Shvedova  3 , Olga S Kopteva  1 , Danila S Guzenkov  1 , Polina A Kudar  1 , Tatiana S Kotomina  1 , Daria S Petrachkova  1 , Elena P Grigorieva  1 , Anna A Lerner  4 , Stanislav V Ponkratov  3
Affiliations

The Clinical and Laboratory Landscape of COVID-19 During the Initial Period of the Pandemic and at the Beginning of the Omicron Era

Yulia A Desheva et al. Viruses. .

Abstract

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underwent significant mutations, resulting in the Omicron variant.

Methods: In this study, we analyzed blood samples from 98 patients with acute coronavirus disease 19 (COVID-19) hospitalized during the initial SARS-CoV-2 wave and the onset of Omicron in 2021. High-resolution melting (HRM) analysis of PCR products was used to analyze RNA extracted from clinical samples collected in July and November 2021 from patients infected with SARS-CoV-2.

Results: HRM analysis revealed a characteristic deletion in the N protein RNA of the virus isolated in November 2021, associated with the Omicron variant. Elevated levels of inflammatory markers and interleukin-6 (IL-6) were observed in both waves of COVID-19. Complement levels and IgG and IgM antibodies to SARS-CoV-2 were detected more often during the second wave. An increase in hemagglutinin-inhibiting (HI) antibodies against influenza viruses was observed in paired blood specimens from moderate to severe COVID-19 patients during both outbreaks.

Conclusions: Patients admitted during both waves of COVID-19 showed a significant rise in inflammatory markers, suggesting that Omicron triggers inflammatory responses. The rapid formation of IgM and IgG in Omicron may indicate a faster immune response. Seasonal flu may negatively impact the clinical course of coronavirus infections.

Keywords: COVID-19; HRM analysis; N protein; Omicron; SARS-CoV-2; complement C3; influenza coinfections.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Phylogenetic analysis of the N protein (1–419 amino acids) of the 33 most representative SARS-CoV-2 variants, including the Wuhan-Hu-1 reference genome. Multiple alignment was performed with the ClustalW method [30]. The branch length represents the number of substitutions per site. The names of the compared genomes of SARS-CoV-2 variants according to the Pango nomenclature [31] are shown in blue.
Figure 2
Figure 2
Molecular genetic analysis of the N protein fragments. In the consensus nucleotide sequence, individual nucleotides are highlighted in different colors. Differences between the original Wuhan variant and the analyzed clinical samples are highlighted in red frames. (a) High-resolution melting curves and nucleotide sequence analysis using the F58-R169 primer set. (b) High-resolution melting curves and nucleotide sequence analysis using the F107-R202 primer set. (c) Multiple alignment in the region of the deletion characteristic of subvariants of the Omicron strain, determined by the primer pair F58-R169. (d) Phylogenetic analysis of the SARS-CoV-2 N protein (1–141 aa) from the Wuhan-Hu-1 reference sequence, as well as two nasopharyngeal washes and Omicron BA.1 and Delta B.1.617.2 strains. MEGA11 was used for phylogenetic analysis, with maximum likelihood statistical methods. Branch lengths represent the number of nucleotide substitutions per site.
Figure 3
Figure 3
The mean levels of inflammatory markers in the blood serum of patients with acute COVID-19 during days 1–3 of hospitalization. Patients were admitted to the hospital in March 2020 and November 2021. *—p < 0.05; ****—p < 0.0001.
Figure 4
Figure 4
The mean levels of inflammatory markers in the blood serum of acute COVID-19 of varying severity during days 1–3 of hospitalization. (a) Patients were admitted to the hospital in March 2020. (b) Patients were admitted to the hospital in November 2021. ***—p < 0.001; ****—p < 0.0001.
Figure 5
Figure 5
Results of the study of the content of early cytokines and type I interferon in the blood of patients with acute COVID-19 during the first 3 days of hospitalization. Patients were admitted to the hospital in March 2020 and November 2021. Reference values for IL-6: 1.3–6.8 pg/mL; for TNF-α: 0–8.21 pg/mL; for IFN-α: <10 pg/mL. ****—p <0.0001.
Figure 6
Figure 6
Results of a study on the content of antibodies specific to the SARS-CoV-2 virus in the blood serum of patients with acute COVID-19 during the first three days of hospitalization. Patients were admitted to the hospital in March 2020 and November 2021. *—p < 0.05.
Figure 7
Figure 7
Proportions of a four-fold and more increase in HI antibodies to the influenza virus among all detected seroconversions.
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