Lung tropism in hospitalized patients following infection with SARS-CoV-2 variants from D614G to Omicron BA.2

Abstract

Background: The genetic and pathogenic characteristics of SARS-CoV-2 have evolved from the original isolated strains; however, the changes in viral virulence have not been fully defined. In this study, we analyzed the association between the severity of the pathogenesis of pneumonia in humans and SARS-CoV-2 variants that have been prevalent to date.

Methods: We examined changes in the variants and tropism of SARS-CoV-2. A total of 514 patients admitted between February 2020 and August 2022 were included and evaluated for pneumonia by computed tomography (CT) as a surrogate of viral tropism.

Results: The prevalence of pneumonia for each variant was as follows: D614G (57%, 65/114), Alpha (67%, 41/61), Delta (49%, 41/84), Omicron BA.1.1 (26%, 43/163), and Omicron BA.2 (11%, 10/92). The pneumonia prevalence in unvaccinated patients progressively declined from 70% to 11% as the variants changed: D614G (56%, 61/108), Alpha (70%, 26/37), Delta (60%, 38/63), BA.1.1 (52%, 15/29), and BA.2 (11%, 2/19). The presence of pneumonia in vaccinated patients was as follows: Delta (16%, 3/19), BA.1.1 (21%, 27/129), and BA.2 (11%, 8/73). Compared with D614G, the areas of lung involvement were also significantly reduced in BA.1.1 and BA.2 variants.

Conclusions: Compared with previous variants, there was a marked decrease in pneumonia prevalence and lung involvement in patients infected with Omicron owing to decreased tropism in the lungs that hindered viral proliferation in the alveolar epithelial tissue. Nevertheless, older, high-risk patients with comorbidities who are infected with an Omicron variant can still develop pneumonia and require early treatment.

Fig. 1. Clinical characteristics by variant.

a Historical transition of SARS-CoV-2 variants identified from February 2020 to August 2022. During this observation period, we identified the following numbers of hospitalized patients infected with the variants: D614G (n = 114), Alpha (n = 61), Delta (n = 84), BA.1.1 (n = 163), and BA.2 (n = 92). b Number of patients (left panel) and percentage of patients (right panel) that developed pneumonia by variant. c Number (left panel) and percentage (right panel) of patients requiring supplemental oxygen by variant. d Number (left panel) and percentage (right panel) of patients requiring ventilator use by variant. e Number (left panel) and percentage (right panel) of patient outcomes by variant. Numbers above bars indicate number of cases.

Fig. 2. Vaccination status and pneumonia findings by variant.

a Vaccination status by variant. Number of patients (left panel) and percentage of patients (right panel) classified as unvaccinated or fully vaccinated (i.e., two or more doses). b, c Presence or absence of pneumonia by variant in unvaccinated (b) and fully vaccinated patients (c). Numbers above bars indicate number of cases.

Fig. 3. Relationship between SARS-CoV-2 variant and CT score.

The CT scores were evaluated semi-quantitatively based on the percentage of lung involvement in the five lung lobes, and the sum of the CT scores (total CT score) was calculated. Box plots show the total CT scores of D614G (n = 114), Alpha (n = 61), Delta (n = 84), BA.1.1 (n = 163), and BA.2. (n = 92). Each box indicates the interquartile range (top: the third quartile; bottom: the first quartile) with a horizontal line indicating the median. Statistical analysis was performed by a t-test, and P-values were adjusted for multiple comparisons.

Fig. 4. Eight fully vaccinated patients showing signs of pneumonia after BA.2 infection.

Chest CT images of the eight fully vaccinated cases who shows COVID-19 pneumoniae. These CT scans were taken immediately upon admission to the hospital.

Fig. 5. Nineteen cases of BA.2 infection in unvaccinated patients.

Chest CT images of the 19 unvaccinated cases who infected with BA.2. These CT scans were taken immediately upon admission to the hospital. Red arrows indicate sites of COVID-19 pneumonia.